Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

Cancer.gov

Genetics of Endocrine and Neuroendocrine Neoplasias discusses inherited syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN1, MEN2, MEN4), familial pheochromocytoma and paraganglioma, Carney-Stratakis syndrome, and familial nonmedullary thyroid cancer. Learn more in this clinician summary.

Cross-sectional study of anal intraepithelial lesions in women with cervical neoplasia without HIV.

PubMed

Heráclio, Sandra A; de Souza, Alex S R; de Souza, Paulo R E; Katz, Leila; Lima Junior, Sergio F; Amorim, Melania M R

2018-02-01

To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia. The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis. There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (P<0.001); subclinical HPV lesions on vulvoscopy (P=0.057) were not associated with anal intraepithelial neoplasia. The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years. © 2017 International Federation of Gynecology and Obstetrics.

Mitotic and apoptotic activity in colorectal neoplasia.

PubMed

Kohoutova, Darina; Pejchal, Jaroslav; Bures, Jan

2018-05-18

Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p < 0.05. Transformation of non-a-A into a-A did not lead to any further significant increase in apoptotic activity, but was related to significant increase in mitotic activity in upper part of crypts and superficial compartment. A significant decrease in apoptotic activity was detected in all three comparments of CRC samples compared to a-A; p < 0.05. No differences in mitotic and apoptotic activity between biopsies in healthy controls and biopsy samples from healthy mucosa in patients with colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. Significant dysregulation of mitosis and apoptosis

In vivo and in vitro hyperspectral imaging of cervical neoplasia

NASA Astrophysics Data System (ADS)

Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

2014-02-01

Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

Immunosignature Differentiation of Non-Infectious Meningoencephalomyelitis and Intracranial Neoplasia in Dogs.

PubMed

Lake, Bathilda B; Rossmeisl, John Henry; Cecere, Julie; Stafford, Phillip; Zimmerman, Kurt L

2018-01-01

A variety of inflammatory conditions of unknown cause (meningoencephalomyelitis of unknown etiology-MUE) and neoplastic diseases can affect the central nervous system (CNS) of dogs. MUE can mimic intracranial neoplasia both clinically, radiologically and even in some cases, histologically. Serum immunosignature protein microarray assays have been used in humans to identify CNS diseases such as Alzheimer's and neoplasia, and in dogs, to detect lymphoma and its progression. This study evaluated the effectiveness of immunosignature profiles for distinguishing between three cohorts of dogs: healthy, intracranial neoplasia, and MUE. Using the learned peptide patterns for these three cohorts, classification prediction was evaluated for the same groups using a 10-fold cross validation methodology. Accuracy for classification was 100%, as well as 100% specific and 100% sensitive. This pilot study demonstrates that immunosignature profiles may help serve as a minimally invasive tool to distinguish between MUE and intracranial neoplasia in dogs.

The Role of Photodynamic Therapy in the Treatment of Vulvar Intraepithelial Neoplasia

PubMed Central

Tosti, Giulio; Iacobone, Anna Daniela; Preti, Eleonora Petra; Vaccari, Sabina; Barisani, Alessia; Pennacchioli, Elisabetta

2018-01-01

Background: vulvar intraepithelial neoplasia is a non-invasive precursor lesion found in 50–70% of patients affected by vulvar squamous cell carcinoma. In the past, radical surgery was the standard treatment for vulvar intraepithelial neoplasia, however, considering the psychological and physical morbidities related to extensive surgery, several less aggressive treatment modalities have been proposed since the late 1970s. Photodynamic therapy is an effective and safe treatment for cutaneous non-melanoma skin cancer, with favorable cosmetic outcomes. Methods: in the present paper, the results of selected studies on photodynamic therapy in the treatment of vulvar intraepithelial neoplasia are reported and discussed. Results: Overall, complete histological response rates ranged between 20% and 67% and symptom response rates ranged between 52% and 89% according to different studies and case series. Conclusions: the real benefit of photodynamic therapy in the setting of vulvar intraepithelial neoplasia lies in its ability to treat multi-focal disease with minimal tissue destruction, preservation of vulvar anatomy and excellent cosmetic outcomes. These properties explain why photodynamic therapy is an attractive option for vulvar intraepithelial neoplasia treatment. PMID:29393881

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy

PubMed Central

Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

2014-01-01

Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. PMID:24385598

Microwave ablation for treatment of hepatic neoplasia in five dogs.

PubMed

Yang, Toni; Case, J Brad; Boston, Sarah; Dark, Michael J; Toskich, Beau

2017-01-01

CASE DESCRIPTION 5 dogs between 9 and 11 years of age were evaluated for treatment of primary (n = 2) or metastatic (3) hepatic neoplasia. CLINICAL FINDINGS Patients were evaluated on an elective (n = 3) or emergency (2) basis. Two dogs with primary hepatic neoplasia were evaluated because of lethargy and inappetence. One dog was referred after an enlarged anal sac was detected via palpation per rectum during a routine physical examination. Two dogs were evaluated on an emergency basis because of lethargy and weakness, and hemoabdomen in the absence of a history of trauma was detected. All 5 dogs underwent thoracic radiography and abdominal ultrasonography, with CT performed in both dogs with primary hepatic neoplasia. All dogs had preoperative evidence of abdominal neoplasia, and none had evidence of thoracic metastasis. TREATMENT AND OUTCOME All dogs underwent ventral midline laparotomy and had diffuse hepatic neoplasia that precluded complete resection. Locoregional treatment with MWA was applied to hepatic lesions (0.5 to 2.5 cm diameter) without procedural complications. Histopathologic diagnoses were biliary adenocarcinoma (n = 1), hemangiosarcoma (2), hepatocellular carcinoma (1), and apocrine gland adenocarcinoma (1). CLINICAL RELEVANCE MWA is being increasingly used as an adjunct in the surgical treatment of human patients with primary and metastatic liver disease. Results of the present small case series suggested that MWA is feasible and potentially effective as an adjunctive treatment for appropriately selected dogs with nonresectable hepatic tumors. Further investigation is indicated.

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy.

PubMed

Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

2014-07-01

This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Advanced colorectal neoplasia was detected in 2544 of the 35,918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7-8. Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

Cancer.gov

Endocrine and neuroendocrine neoplasias may be inherited in syndromes such as multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), familial pheochromocytoma and paraganglioma, and Carney-Stratakis syndrome. Learn about the genetics, clinical manifestations, and management of these hereditary cancer syndromes in this expert-reviewed summary.

Malignant Neoplasia of the Sex Skin in 2 Chimpanzees (Pan troglodytes).

PubMed

Beck, Amanda P; Magden, Elizabeth R; Buchl, Stephanie J; Baze, Wallace B

2016-04-01

This report describes 2 cases of spontaneous malignant neoplasia within the sex skin of aged female chimpanzees. In both cases, the initial presentation resembled nonhealing traumatic wounds to the sex skin, with different degrees of infection, ulceration, and tissue necrosis. Histopathology of the lesions confirmed the diagnosis of squamous cell carcinoma in one case and of adenocarcinoma with metastasis in the other. Advanced age and previous trauma likely contributed to the development of the neoplasias in both cases; long-term sun exposure may also have contributed to the development of the squamous cell carcinoma. To our knowledge, these 2 cases represent the first reports of sex skin neoplasia in chimpanzees.

Risk factors for persistent gestational trophoblastic neoplasia.

PubMed

Kuyumcuoglu, Umur; Guzel, Ali Irfan; Erdemoglu, Mahmut; Celik, Yusuf

2011-01-01

This retrospective study evaluated the risk factors for persistent gestational trophoblastic disease (GTN) and determined their odds ratios. This study included 100 cases with GTN admitted to our clinic. Possible risk factors recorded were age, gravidity, parity, size of the neoplasia, and beta-human chorionic gonadotropin levels (beta-hCG) before and after the procedure. Statistical analyses consisted of the independent sample t-test and logistic regression using the statistical package SPSS ver. 15.0 for Windows (SPSS, Chicago, IL, USA). Twenty of the cases had persistent GTN, and the differences between these and the others cases were evaluated. The size of the neoplasia and histopathological type of GTN had no statistical relationship with persistence, whereas age, gravidity, and beta-hCG levels were significant risk factors for persistent GTN (p < 0.05). The odds ratios (95% confidence interval (CI)) for age, gravidity, and pre- and post-evacuation beta-hCG levels determined using logistic regression were 4.678 (0.97-22.44), 7.315 (1.16-46.16), 2.637 (1.41-4.94), and 2.339 (1.52-3.60), respectively. Patient age, gravidity, and beta-hCG levels were risk factors for persistent GTN, whereas the size of the neoplasia and histopathological type of GTN were not significant risk factors.

Neoplasia in Turner syndrome. The importance of clinical and screening practices during follow-up.

PubMed

Larizza, Daniela; Albanesi, Michela; De Silvestri, Annalisa; Accordino, Giulia; Brazzelli, Valeria; Maffè, Gabriella Carnevale; Calcaterra, Valeria

2016-05-01

Turmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients. We retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS. A total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found. In our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

PubMed Central

Sharma, Anjana; Panda, Anita

2007-01-01

Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

Equine orbital neoplasia: a review of 10 cases (1983-1998).

PubMed Central

Baptiste, K E; Grahn, B H

2000-01-01

The clinical manifestations, laboratory findings, and survival times of 10 horses with orbital neoplasms are reported. In all cases, orbital neoplasms were malignant and locally invasive with no defined surgical circumscribed edges. It was often difficult to identify the primary cell type of the neoplasia in histologic specimens due to the poorly differentiated, anaplastic nature of the majority of cases. All except one horse were eventually euthanized 2 mo to 5 y after diagnosis due to poor response to treatment, metastasis, or unrelenting orbital neoplasia. Mean survival time increased with surgical treatment, but no significant difference was found among no treatment, chemotherapy, surgical mass removal, or exenteration/enucleation. Equine practitioners should be aware of the marked difference in prognosis of orbital neoplasms compared with ocular or localized eyelid neoplasia. Images Figure 1. Figure 2. Figure 3. PMID:10769765

Unregulated smooth-muscle myosin in human intestinal neoplasia.

PubMed

Alhopuro, Pia; Phichith, Denis; Tuupanen, Sari; Sammalkorpi, Heli; Nybondas, Miranda; Saharinen, Juha; Robinson, James P; Yang, Zhaohui; Chen, Li-Qiong; Orntoft, Torben; Mecklin, Jukka-Pekka; Järvinen, Heikki; Eng, Charis; Moeslein, Gabriela; Shibata, Darryl; Houlston, Richard S; Lucassen, Anneke; Tomlinson, Ian P M; Launonen, Virpi; Ristimäki, Ari; Arango, Diego; Karhu, Auli; Sweeney, H Lee; Aaltonen, Lauri A

2008-04-08

A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia.

Endoscopic submucosal dissection for early Barrett's neoplasia.

PubMed

Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas; Prat, Frédéric

2016-04-01

The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett's esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett's neoplasia. All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett's esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett's segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. In this early experience, ESD yielded a moderate curative resection rate in Barrett's neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett's neoplasia.

Diagnostic accuracy of three biopsy techniques in 117 dogs with intra-nasal neoplasia.

PubMed

Harris, B J; Lourenço, B N; Dobson, J M; Herrtage, M E

2014-04-01

To determine if nasal biopsies taken at rhinoscopy are more accurate for diagnosing neoplasia than biopsies taken blindly or using advanced imaging for guidance. A retrospective study of 117 dogs with nasal mass lesions that were divided into three groups according to the method of nasal biopsy collection; advanced imaging-guided, rhinoscopy-guided and blind biopsy. Signalment, imaging and rhinoscopic findings, and histopathological diagnosis were compared between groups. The proportion of first attempt biopsies confirming neoplasia were determined for each group. There were no statistically significant differences in the proportion of biopsies that confirmed neoplasia obtained via advanced imaging-guided, rhinoscopy-guided or blind biopsy techniques. In dogs with a high index of suspicion of nasal neoplasia, blind biopsy may be as diagnostic as rhinoscopy-guided biopsy. Repeated biopsies are frequently required for definitive diagnosis. © 2014 British Small Animal Veterinary Association.

Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia.

PubMed

Drees, R; Forrest, L J; Chappell, R

2009-07-01

Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity.

Computed tomographic colonography for colorectal cancer screening: risk factors for the detection of advanced neoplasia.

PubMed

Hassan, Cesare; Pooler, B Dustin; Kim, David H; Rinaldi, Antonio; Repici, Alessandro; Pickhardt, Perry J

2013-07-15

The objective of this study was to determine whether age, sex, a positive family history of colorectal cancer, and body mass index (BMI) are important predictors of advanced neoplasia in the setting of screening computed tomographic colonography (CTC). Consecutive patients who were referred for first-time screening CTC from 2004 to 2011 at a single medical center were enrolled. Results at pathology were recorded for all patients who underwent polypectomy. Logistic regression was used to identify significant predictor variables for advanced neoplasia (any adenoma ≥ 10 mm or with villous component, high-grade dysplasia, or adenocarcinoma). Odds ratios (ORs) were used to express associations between the study variables (age, sex, BMI, and a positive family history of colorectal cancer) and advanced neoplasia. In total, 7620 patients underwent CTC screening. Of these, 276 patients (3.6%; 95% confidence interval [CI], 3.2%-4.1%) ultimately were diagnosed with advanced neoplasia. At multivariate analysis, age (mean OR per 10-year increase, 1.8; 95% CI, 1.6-2.0) and being a man (OR, 1.7; 95% CI, 1.3-2.2) were independent predictors of advanced neoplasia, whereas BMI and a positive family history of colorectal cancer were not. The number needed to screen to detect 1 case of advanced neoplasia varied from 51 among women aged ≤ 55 years to 10 among men aged >65 years. The number of post-CTC colonoscopies needed to detect 1 case of advanced neoplasia varied from 2 to 4. Age and sex were identified as important independent predictors of advanced neoplasia risk in individuals undergoing screening CTC, whereas BMI and a positive family history of colorectal cancer were not. These results have implications for appropriate patient selection. © 2013 American Cancer Society.

Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004-2014).

PubMed

Beatrice, Laura; Boretti, Felicitas Schär; Sieber-Ruckstuhl, Nadja S; Mueller, Claudia; Kümmerle-Fraune, Claudia; Hilbe, Monika; Grest, Paula; Reusch, Claudia E

2018-03-17

Multiple endocrine neoplasia (MEN) is a well-known syndrome in human medicine, whereas only a few cases of concurrent endocrine neoplasias have been reported in dogs and cats. The aim of this study was to evaluate the prevalence of concurrent endocrine neoplasias in dogs and cats at our clinic, identify possible breed and sex predispositions and investigate similarities with MEN syndromes in humans. Postmortem reports of 951 dogs and 1155 cats that died or were euthanased at the Clinic for Small Animal Internal Medicine, University of Zurich, between 2004 and 2014 were reviewed, and animals with at least two concurrent endocrine neoplasias and/or hyperplasias were included. Twenty dogs and 15 cats met the inclusion criteria. In dogs, the adrenal glands were most commonly affected. Multiple tumours affecting the adrenal glands and the association of these tumours with pituitary adenomas were the most common tumour combinations. Only one dog had a combination resembling human MEN type 1 syndrome (pituitary adenoma and insulinoma). In cats, the thyroid glands were most commonly affected and there were no similarities to human MEN syndromes. The prevalence of concurrent endocrine neoplasia was 2.1 per cent in dogs and 1.3 per cent in cats and MEN-like syndromes are very rare in these species. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia

PubMed Central

Drees, R.; Forrest, L. J.; Chappell, R.

2009-01-01

Objectives Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Methods Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Results Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. Clinical Significance We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity. PMID:19508490

Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women With and Without Genital Neoplasia.

PubMed

Bregar, Amy J; Cronin, Beth; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa; Robison, Katina

2018-04-01

The aim of the study was to compare the prevalence, genotypes, and rates of concomitant anal and cervical high-risk human papillomavirus (HR-HPV) in women with and without a history of HPV-related genital neoplasia. This was a prospective cohort study conducted from December 2012 to February 2014. Women with a history of neoplasia were considered the high-risk group. Women without a history of neoplasia were considered the low-risk group. Cervical and anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for anoscopy. One hundred eighty-four women met inclusion criteria. High-risk HPV was detected in the anal canal of 17.4% of the high-risk group and 1.5% of the low-risk group (p = .003). High-risk HPV was detected in the cervix of 30.5% of the high-risk group and 7.6% of the low-risk group (p < .001). Concomitant anal and cervical high-risk HPV was detected in 4.4% of the high-risk group and was not detected in the low-risk group (p = .2). Among women with anal intraepithelial neoplasia 2 or greater (n = 5), 60% had HR-HPV detected in the anal canal while none had HR-HPV detected in the cervix. Women with a history of genital neoplasia are more likely to be positive for anal and cervical HR-HPV compared with women without a history of genital neoplasia. Although there was no significant difference in rates of concomitant HR-HPV between low- and high-risk groups, HR-HPV can be found concomitantly in the anus and the cervix and may be associated with anal intraepithelial neoplasia or carcinoma.

Endoscopic submucosal dissection for early Barrett’s neoplasia

PubMed Central

Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas

2015-01-01

Introduction The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett’s esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett’s neoplasia. Methods All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett’s esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Results Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett’s segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. Conclusion In this early experience, ESD yielded a moderate curative resection rate in Barrett’s neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett’s neoplasia. PMID:27087948

Prevalence of colorectal neoplasia among young African Americans and Hispanic Americans

PubMed Central

Ashktorab, Hassan; Paydar, Mansour; Namin, Hassan Hassanzadeh; Sanderson, Andrew; Begum, Rehana; Brim, Hassan; Panchal, Heena; Lee, Edward; Kibreab, Angesom; Nouraie, Mehdi; Laiyemo, Adeyinka O.

2014-01-01

Background The disproportionately higher incidence of, and mortality from colorectal cancer (CRC) among African Americans (AA) led the American College of Gastroenterology to recommend screening starting at age 45 in 2005. Aim To determine the prevalence of colorectal neoplasia among 40–49 years old inner city African Americans (AA) and Hispanic Americans (HA). Methods We reviewed the medical records of 2435 inner city AA and HA who underwent colonoscopy regardless of indication and compared the prevalence of colorectal neoplasia between AA and HA patients. We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Results There were 2,163 AA and 272 HA. There were 57% women in both groups. A total of 158 (7%) AA and 9 (3%) HA (P = 0.014) underwent the procedures for CRC screening. When compared to HA, AA had higher prevalence of any polyp (35% versus 18%, OR = 2.53; 95% CI: 1.82–3.52). Overall, AA had higher prevalence of colorectal neoplasia (adenoma and cancer) when compared to HA (16% versus 10%; OR = 1.68; 95% CI: 1.10–2.56). Conclusion We observed a higher frequency of colorectal neoplasia among 40–49 year-old AA as compared to HA suggesting an increased susceptibility to CRC risk in this population. PMID:24193352

Prevalence of colorectal neoplasia among young African Americans and Hispanic Americans.

PubMed

Ashktorab, Hassan; Paydar, Mansour; Namin, Hassan Hassanzadeh; Sanderson, Andrew; Begum, Rehana; Brim, Hassan; Panchal, Heena; Lee, Edward; Kibreab, Angesom; Nouraie, Mehdi; Laiyemo, Adeyinka O

2014-02-01

The disproportionately higher incidence of and mortality from colorectal cancer (CRC) among African Americans (AA) led the American College of Gastroenterology to recommend screening starting at age 45 in 2005. The purpose of this study was to determine the prevalence of colorectal neoplasia among 40-49-year-old inner city AA and Hispanic Americans (HA). We reviewed the medical records of 2,435 inner city AA and HA who underwent colonoscopy regardless of indication and compared the prevalence of colorectal neoplasia between AA and HA patients. We used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI). There were 2,163 AAs and 272 HA. There were 57 % women in both groups. A total of 158 (7 %) AA and 9 (3 %) HA (P = 0.014) underwent the procedures for CRC screening. When compared to HAs, AAs had higher prevalence of any polyp (35 vs. 18 %, OR = 2.53; 95 % CI 1.82-3.52). Overall, AA had higher prevalence of colorectal neoplasia (adenoma and cancer) when compared to HAs (16 vs. 10 %; OR = 1.68; 95 % CI 1.10-2.56). We observed a higher frequency of colorectal neoplasia among 40-49-year-old AAs as compared to HAs suggesting an increased susceptibility to CRC risk in this population.

Severe Phenotype of Keratitis-Ichthyosis-Deafness Syndrome With Presumed Ocular Surface Squamous Neoplasia.

PubMed

Serrano-Ahumada, Ana Silvia; Cortes-González, Vianney; González-Huerta, Luz María; Cuevas, Sergio; Aguilar-Lozano, Luis; Villanueva-Mendoza, Cristina

2018-02-01

The aim of this study was to describe a case of severe keratitis-ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia. The affected patient underwent complete ocular and systemic examinations. The molecular studies included polymerase chain reaction amplification and automated DNA sequencing of the complete gap junction beta-2 (GJB2) gene coding sequence. A 30-year-old man presented with generalized erythro-hyperkeratosis and deafness and complaints of decreased visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal erosion, vascularization, and a gray gelatinous lesion partially covering the right cornea, suggestive of squamous neoplasia. The clinical features were characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous neoplasia was treated with topical interferon α2b. KID syndrome is a very rare disease that has been reported with an incremental incidence of squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we presented a case of severe systemic KID syndrome with ocular surface squamous neoplasia.

Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients.

PubMed

Pouw, Roos E; Seewald, Stefan; Gondrie, Joep J; Deprez, Pierre H; Piessevaux, Hubert; Pohl, Heiko; Rösch, Thomas; Soehendra, Nib; Bergman, Jacques J

2010-09-01

Endoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barrett's oesophagus with early neoplasia. Retrospective cohort study. Four tertiary referral centres. 169 patients (151 males, age 64 years (IQR 57-71), Barrett's oesophagus 3 cm (IQR 2-5)) with early neoplasia in Barrett's oesophagus < or = 5 cm, without deep submucosal infiltration or lymph node metastases, treated by SRER between January 2000 and September 2006. Endoscopic resection every 4-8 weeks, until complete endoscopic and histological eradication of Barrett's oesophagus and neoplasia. According to intention-to-treat analysis complete eradication of all neoplasia and all intestinal metaplasia by the end of the treatment phase was reached in 97.6% (165/169) and 85.2% (144/169) of patients, respectively. One patient had progression of neoplasia during treatment and died of metastasised adenocarcinoma (0.6%). After median follow-up of 32 months (IQR 19-49), complete eradication of neoplasia and intestinal metaplasia was sustained in 95.3% (161/169) and 80.5% (136/169) of patients, respectively. Acute, severe complications occurred in 1.2% of patients, and 49.7% of patients developed symptomatic stenosis. SRER of Barrett's oesophagus < or = 5 cm containing early neoplasia appears to be an effective treatment modality with a low rate of recurrent lesions during follow-up. The procedure, however, is technically demanding and is associated with oesophageal stenosis in half of the patients.

Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

PubMed

Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

2013-02-01

To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

Systematic review with meta-analysis: the incidence of advanced neoplasia after polypectomy in patients with and without low-risk adenomas.

PubMed

Hassan, C; Gimeno-García, A; Kalager, M; Spada, C; Zullo, A; Costamagna, G; Senore, C; Rex, D K; Quintero, E

2014-05-01

Patients with one to two tubular adenomas <1 cm in size without high-grade dysplasia (low-risk group) are considered at low risk for colorectal cancer. However, it is uncertain whether they have the same risk of subsequent advanced neoplasia as those with no neoplasia at baseline colonoscopy. To compare incidence of metachronous advanced neoplasia between patients in the low-risk adenoma group and those without neoplasia at index colonoscopy. Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1992-2013. Studies comparing the incidence of post-polypectomy advanced neoplasia (adenomas ≥10 mm/high-grade dysplasia/villous or cancer) between the low-risk group and patients without colorectal neoplasia at the first colonoscopy were included. Detection rates for advanced neoplasia at endoscopic surveillance were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random-effect models. Inter-study heterogeneity was assessed using the I(2) statistic. Seven studies provided data on 11 387 patients. Mean surveillance periods ranged between 2 and 5 years. Altogether, 267 patients with post-polypectomy advanced neoplasia were detected in the two groups. The incidence of advanced neoplasia was 1.6% (119/7308) in those without neoplasia and 3.6% (148/4079) in those with low-risk adenoma, respectively, corresponding to a relative risk of 1.8 (95% CI: 1.3-2.6). Inter-study heterogeneity was only moderate (I(2) : 37%). No publication bias was present. Patients with low-risk adenomas at baseline had a higher risk of metachronous advanced neoplasia than the group with no adenomas at baseline, though the absolute risk was low in both groups. © 2014 John Wiley & Sons Ltd.

Linear array ultrasonography to stage rectal neoplasias suitable for local treatment.

PubMed

Ravizza, Davide; Tamayo, Darina; Fiori, Giancarla; Trovato, Cristina; De Roberto, Giuseppe; de Leone, Annalisa; Crosta, Cristiano

2011-08-01

Because of the many therapeutic options available, a reliable staging is crucial for rectal neoplasia management. Adenomas and cancers limited to the submucosa without lymph node involvement may be treated locally. The aim of this study is to evaluate the diagnostic accuracy of endorectal ultrasonography in the staging of neoplasias suitable for local treatment. We considered all patients who underwent endorectal ultrasonography between 2001 and 2010. The study population consisted of 92 patients with 92 neoplasias (68 adenocarcinomas and 24 adenomas). A 5 and 7.5MHz linear array echoendoscope was used. The postoperative histopathologic result was compared with the preoperative staging defined by endorectal ultrasonography. Adenomas and cancers limited to the submucosa were considered together (pT0-1). The sensitivity, specificity, overall accuracy rate, positive predictive value, and negative predictive value of endorectal ultrasonography for pT0-1 were 86%, 95.6%, 91.3%, 94.9% and 88.7%. Those for nodal involvement were 45.4%, 95.5%, 83%, 76.9% and 84%, with 3 false positive results and 12 false negative. For combined pT0-1 and pN0, endorectal ultrasonography showed an 87.5% sensitivity, 95.9% specificity, 92% overall accuracy rate, 94.9% positive predictive value and 90.2% negative predictive value. Endorectal linear array ultrasonography is a reliable tool to detect rectal neoplasias suitable for local treatment. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database.

PubMed

Giusti, Francesca; Cianferotti, Luisella; Boaretto, Francesca; Cetani, Filomena; Cioppi, Federica; Colao, Annamaria; Davì, Maria Vittoria; Faggiano, Antongiulio; Fanciulli, Giuseppe; Ferolla, Piero; Ferone, Diego; Fossi, Caterina; Giudici, Francesco; Gronchi, Giorgio; Loli, Paola; Mantero, Franco; Marcocci, Claudio; Marini, Francesca; Masi, Laura; Opocher, Giuseppe; Beck-Peccoz, Paolo; Persani, Luca; Scillitani, Alfredo; Sciortino, Giovanna; Spada, Anna; Tomassetti, Paola; Tonelli, Francesco; Brandi, Maria Luisa

2017-11-01

The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database. The Italian multiple endocrine neoplasia type 1 database includes 475 patients (271 women and 204 men), of whom 383 patients (80.6%) were classified as familial cases (from 136 different pedigrees), and 92 (19.4%) patients were sporadic cases. A MEN1 mutation was identified in 92.6% of familial cases and in 48.9% of sporadic cases. Four hundred thirty-six patients were symptomatic, presenting primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.

PubMed

Owston, Michael A; Ramsay, Edward C; Rotstein, David S

2008-12-01

A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids.

Alternate pathogenesis of systemic neoplasia in the bivalve mollusc Mytilus.

PubMed

Moore, J D; Elston, R A; Drum, A S; Wilkinson, M T

1991-09-01

The proliferative disease systemic neoplasia, also termed hemic neoplasia or disseminated sarcoma, was studied in four Puget Sound, Washington populations of the bay mussel (Mytilus sp.). Using flow cytometric measurement of DAPI-stained cells withdrawn from the hemolymph, DNA content frequency histograms were generated for 73 individuals affected by the disease. The cells manifesting systemic neoplasia were found to exist as either of two separate types, characterized by G0G1 phase nuclear DNA contents of either approximately 4.9 x haploid (pentaploid form) or approximately 3.8 x haploid (tetraploid form). The two disease forms were found to coexist in all four mussel populations sampled, with overall relative prevalences of 66% pentaploid form, 29% tetraploid form, and 5% exhibiting both disease forms simultaneously. These findings represent the first unequivocal demonstration of multiple cell types in a bivalve neoplasia. The two forms appear to represent separate pathogenetic processes rather than sequential stages of a single pathogenesis. Two cell cycling parameters associated with proliferative activity were employed to compare the alternate forms: (i) the percentage of cells assigned to the DNA Synthesis (S) phase of the neoplastic cell cycle, and (ii) the proportion of neoplastic cell mitotic figures in hemocytological preparations. Mean values for both parameters were significantly higher for mussels with the tetraploid form of the disease, suggesting a higher rate of proliferation relative to the pentaploid form. Qualitatively, cells of the tetraploid form contained slightly lower nuclear and cytoplasmic volumes compared to those of the pentaploid form. An observed wide variation in neoplastic cell nuclear size within either disease form may reflect the distribution of cells in the G0G1, S, and G2M phases of the cell cycle. Potential etiologic relationships between the two forms are discussed.

[Results of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years from 1993 to 2012].

PubMed

Korbeľ, M; Šufliarsky, J; Danihel, Ľ; Vojtaššák, J; Nižňanská, Z

2016-01-01

Analysis and epidemiology of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years 1993-2012. Retrospective epidemiological national study. Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic, Bratislava. Retrospective analysis results of gestational trophoblastic neoplasia treatment according to prognostic scoring and staging system FIGO/WHO in Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic Bratislava in the years 1993-2012. The treatment of gestational trophoblastic neoplasia (GTN) in the Czech and Slovak Republics started in 1955 and lasted till 1993. After the split of the former Czechoslovakia the Centre for gestational trophoblastic disease was created in Slovakia. 75 patients were treated in this Centre in the years 1993-2012. According to prognostic scoring and staging system FIGO/WHO 56 (75%) patients had low-risk gestational trophoblastic neoplasia and 19 (25%) of patients had high-risk gestational trophoblastic neoplasia. There were 41 patients (55%), 2 (3%), 24 (32%) and 8 (11%) in stage I., II., III. and IV. respectively. Total curability rate was 94.7% and mortality rate was 5.3%. Curability rate 100% was achieved in stage I & II and all placental site trophoblastic tumours (PSTT), 98.3% in stage III and 50% stage IV. In the years 1993-2012 the incidence of choriocarcinoma was one in 76 273 pregnancies and one in 53 203 deliveries. The incidence of other gestational trophoblastic neoplasia in the same years was for PSTT one in 533 753 pregnancies and one in 372 422 deliveries, invasive mole one in 145 611 pregnancies and one in 101 569 deliveries, and persistent GTN one in 40 043 pregnancies and one in 27 932 deliveries. 225-241 patients were treated in the same period of time in the Czech Republic with curability rate 98.2-98. 3%. Early detection and treatment in the centre for trophoblastic disease are crucial points in the manage-ment of gestational

Orbital neoplasia in 23 dogs.

PubMed

Kern, T J

1985-03-01

Medical records of 23 dogs with histologically documented orbital neoplasia and admitted to the New York State College of Veterinary Medicine between 1975 and 1984 were reviewed. Almost all (91%) of the tumors were classified as malignant; 74% of the tumors arose as primary neoplasms within the orbit. Eleven tumor types of connective tissue, bone, epithelial, and hemolymphatic origin were represented. The typically afflicted dog was purebred, female, and middle-aged. Review of this series confirmed the clinical impression that orbital neoplasms in dogs are aggressive malignancies with poor long-term prognosis.

Detection of Human Papillomavirus Infection in Patients with Vaginal Intraepithelial Neoplasia.

PubMed

Lamos, Cristina; Mihaljevic, Charlotte; Aulmann, Sebastian; Bruckner, Thomas; Domschke, Christoph; Wallwiener, Markus; Paringer, Carmen; Fluhr, Herbert; Schott, Sarah; Dinkic, Christine; Brucker, Janina; Golatta, Michael; Gensthaler, Lisa; Eichbaum, Michael; Sohn, Christof; Rom, Joachim

2016-01-01

Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions. 67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System). All 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL

Investigating work-related neoplasia associated with solar radiation.

PubMed

Turner, S; Forman, S D; McNamee, R; Wilkinson, S M; Agius, R

2015-01-01

Both solar and non-solar exposures associated with occupation and work tasks have been reported as skin carcinogens. In the UK, there are well-established surveillance schemes providing relevant information, including when exposures took place, occupation, location of work and dates of symptom onset and diagnosis. To add to the evidence on work-related skin neoplasia, including causal agents, geographical exposure and time lag between exposure and diagnosis. This study investigated incident case reports of occupational skin disease originating from clinical specialists in dermatology reporting to a UK-wide surveillance scheme (EPIDERM) by analysing case reports of skin neoplasia from 1996 to 2012 in terms of diagnosis, employment, suspected causal agent and symptom onset. The suspected causal agent was 'sun/sunlight/ultraviolet light' in 99% of the reported work-related skin neoplasia cases. Most cases reported (91%) were in males, and the majority (62%) were aged over 65 at the time of reporting. More detailed information on exposure was available for 42% of the cases, with the median time from exposure to symptom onset ranging from 44 (melanoma) to 57 (squamous cell carcinoma) years. Irrespective of diagnostic category, the median duration of exposure to 'sun/sunlight/ultraviolet light' appeared longer where exposures occurred in the UK (range 39-51 years) rather than outside the UK (range 2.5-6.5 years). It is important to provide effective information about skin protection to workers exposed to solar radiation, especially to outdoor workers based outside the UK. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Diagnosis, treatment and outcome of orbital neoplasia in dogs: a retrospective study of 44 cases.

PubMed

Hendrix, D V; Gelatt, K N

2000-03-01

Forty-four dogs with confirmed orbital neoplasia were studied. Eighteen tumour types were represented and 95 per cent of the neoplasms were classified as malignant. The tumour types most commonly diagnosed were osteosarcoma, fibrosarcoma and nasal adenocarcinoma. Thirty-six per cent of the dogs had at least one clinical sign that was compatible with a diagnosis of orbital abscessation or cellulitis. Fifty-six per cent of the dogs, where follow-up information was available, were euthanased or had died within six months of diagnosis, while 19 per cent of the total were still alive after one year post-diagnosis. Cytological examination was diagnostic for orbital neoplasia in 49 per cent of the fine needle aspirates of the retrobulbar space. In contrast, 56 per cent of the non-surgical biopsies were diagnostic for orbital neoplasia. Of those dogs that had died or been euthanased within six months of diagnosis, only 22 per cent had undergone some form of therapy for orbital neoplasia. In comparison, 86 per cent of dogs surviving longer than six months post-diagnosis had undergone such therapy.

Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis

PubMed Central

Dulai, Parambir S; Marquez, Evelyn; Khera, Rohan; Prokop, Larry J; Limburg, Paul J; Gupta, Samir; Murad, Mohammad Hassan

2016-01-01

Objective To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. Data sources Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries. Study selection Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events. Data extraction Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria. Results 15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but

Disparities in prevalence, location, and shape characteristics of colorectal neoplasia between South Korean and U.S. patients.

PubMed

Cha, Jae Myung; Kozarek, Richard A; La Selva, Danielle; Gluck, Michael; Ross, Andrew; Chiorean, Michael; Koch, Johannes; Lin, Otto S

2015-12-01

Colon cancer screening is being introduced in many countries, but standard Western screening approaches may not be appropriate for Asian societies if differences in colon cancer epidemiology exist. Comparative analysis of colorectal neoplasia patterns in South Korean and Western subjects has implications for appropriate screening approaches in non-Western societies. The results of concurrent screening colonoscopies performed in average-risk patients 50 to 69 years old in 2 teaching hospitals, Kyung Hee University Hospital (Seoul, South Korea) and Virginia Mason Medical Center (Seattle, Wash), were compared with respect to prevalence, histologic features, anatomic distribution, and shape characteristics of colorectal neoplasia. The U.S. (n = 3460) and South Korean (n = 2193) cohorts were similar with regard to the prevalence of adenomas (28.5% vs 29.8%, respectively, P = .312) and advanced neoplasia (6.4% vs 5.4%, respectively, P = .102), but the proportion of proximal adenomas was greater in the U.S. cohort (62.8% vs 45.9%, P < .001). The prevalence of adenomas and advanced neoplasia was similar in male patients, but there was a greater prevalence of neoplasia (23.5% vs 18.8%, P = .006) and advanced neoplasia (5.1% vs 2.7%, P < .001) in U.S. women than South Korean women. When large (≥10 mm) adenomas were considered, proximal location and nonpolypoid (flat) shape were more common in the U.S. cohort (79.4% vs 37.1%, P = .003 and 43.5% vs 12.3%, P < .001, respectively). The overall prevalence of large flat adenomas in the U.S. cohort was 5 times that of the South Korean cohort (2.6% vs 0.5%, P < .001). Adjustment for sex ratio discrepancies (48.3% men in the U.S. cohort vs 60.8% in the South Korean cohort, P < .001) did not result in any significant changes in the conclusions. Compared with Westerners, South Koreans have a more distal distribution of adenomas and advanced neoplasia and lower prevalence of large flat adenomas. South Korean women have a lower

Predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients successfully treated with methotrexate alone.

PubMed

Couder, Florence; Massardier, Jérôme; You, Benoît; Abbas, Fatima; Hajri, Touria; Lotz, Jean-Pierre; Schott, Anne-Marie; Golfier, François

2016-07-01

Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia

The Early Detection of Pancreatic Cancer: What Will it Take to Diagnose and Treat Curable Pancreatic Neoplasia?

PubMed Central

Lennon, Anne Marie; Wolfgang, Christopher L.; Canto, Marcia Irene; Klein, Alison P.; Herman, Joseph M.; Goggins, Michael; Fishman, Elliot K.; Kamel, Ihab; Weiss, Matthew J.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.

2014-01-01

Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific, approaches for screening for curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. PMID:24924775

Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett's-associated neoplasia.

PubMed

Thekkek, Nadhi; Lee, Michelle H; Polydorides, Alexandros D; Rosen, Daniel G; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2015-05-01

Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett's-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett's-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett's esophagus (BE), dysplasia, oresophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope(HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC = 0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett's-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance.

Disparities in the Clinical Evolution of Anal Neoplasia in an HIV-Infected Cohort.

PubMed

Cachay, Edward R; Agmas, Wollelaw; Christopher Mathews, Wm

2018-02-01

A recent meta-analysis suggested that anal intraepithelial neoplasia and invasive anal cancer are more prevalent among black men having sex with men (MSM). We conducted a retrospective cohort of HIV-infected adult patients under care between 2001 and 2012. Disparities in clinical evolution of anal intraepithelial neoplasia to high-grade squamous intraepithelial lesion (HSIL) and invasive anal cancer were evaluated in a three-state Markov model adjusted for cytology misclassification. We studied sociodemographic covariate effects for each state transition using multivariable models controlling for antiretroviral therapy and infrared coagulation treatment of HSIL. Among 2804 patients with a median age of 40 years, 78% were MSM and 38% non-white. There were no disparities in HSIL prevalence (14%) by age, sex, race, or risk group. After 4.0 years of follow-up, 23 patients developed invasive anal cancer. Females and black patients had lower transition rates from 40 had lower rates of both neoplasia nor with post-baseline progression of anal intraepithelial neoplasia.

Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

PubMed

Koeneman, M M; Kruse, A J; Kooreman, L F S; Zur Hausen, A; Hopman, A H N; Sep, S J S; Van Gorp, T; Slangen, B F M; van Beekhuizen, H J; van de Sande, A J M; Gerestein, C G; Nijman, H W; Kruitwagen, R F P M

2017-02-07

The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential

PubMed Central

Mitchell, Rod T; Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher JH; O’Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland

2014-01-01

Testicular germ cell cancer develops from pre-malignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4+/ MAGEA4−) into pre-spermatogonia (OCT4−/MAGEA4+). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesised that cells expressing an immature (OCT4+/MAGEA4−) germ cell profile would exhibit an increased proliferation rate compared to those with a mature profile (OCT4+/ MAGEA4+). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with pre-invasive disease, seminoma and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4+/MAGEA4- cells showed a significantly increased rate of proliferation compared with the OCT4+/MAGEA4+ population (12.8 v 3.4%, p<0.0001) irrespective of histological tumour type, reflected in the predominance of OCT4+/MAGEA4− cells in the invasive tumour component. Surprisingly, OCT4+/MAGEA4− cells in patients with pre-invasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 v 10.2 v 7.2%, p<0.05 respectively). In conclusion, this study has demonstrated that OCT4+/MAGEA4

Can the Ni classification of vessels predict neoplasia? A systematic review and meta-analysis.

PubMed

Mehlum, Camilla S; Rosenberg, Tine; Dyrvig, Anne-Kirstine; Groentved, Aagot Moeller; Kjaergaard, Thomas; Godballe, Christian

2018-01-01

The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non-neoplasia. We aimed to evaluate the ability of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia. PubMed, Embase, Cochrane, and Scopus databases. A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We systematically searched for publications from 2011 until 2016. All retrieved studies were reviewed and qualitatively assessed. The pooled sensitivity and specificity of the Ni classification with two different cutoffs were calculated, and bubble and summary receiver operating characteristics plots were created. The combined sensitivity of five studies (n = 687) with Ni type IV-V defined as test-positive was 0.89 (95% confidence interval [CI]: 0.76-0.95), and specificity was 0.82 (95% CI: 0.72-0.89). The equivalent combined sensitivity of four studies (n = 624) with Ni type V defined as test-positive was 0.82 (95% CI: 0.75-0.87), and specificity was 0.93 (95% CI: 0.82-0.97). The diagnostic accuracy of the Ni classification in predicting neoplasia was high, without significant difference between the two analyzed cutoff values. Implementation of the proposed ELS classification of vascular changes seems reasonable from a clinical perspective, with comparable accuracy. Attention must be drawn to the accompanying risk of exposing patients to unnecessary surgery. Laryngoscope, 128:168-176, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Analysis of digitized cervical images to detect cervical neoplasia

NASA Astrophysics Data System (ADS)

Ferris, Daron G.

2004-05-01

Cervical cancer is the second most common malignancy in women worldwide. If diagnosed in the premalignant stage, cure is invariably assured. Although the Papanicolaou (Pap) smear has significantly reduced the incidence of cervical cancer where implemented, the test is only moderately sensitive, highly subjective and skilled-labor intensive. Newer optical screening tests (cervicography, direct visual inspection and speculoscopy), including fluorescent and reflective spectroscopy, are fraught with certain weaknesses. Yet, the integration of optical probes for the detection and discrimination of cervical neoplasia with automated image analysis methods may provide an effective screening tool for early detection of cervical cancer, particularly in resource poor nations. Investigative studies are needed to validate the potential for automated classification and recognition algorithms. By applying image analysis techniques for registration, segmentation, pattern recognition, and classification, cervical neoplasia may be reliably discriminated from normal epithelium. The National Cancer Institute (NCI), in cooperation with the National Library of Medicine (NLM), has embarked on a program to begin this and other similar investigative studies.

Homozygotes for the autosomal dominant neoplasia syndrome (MEN1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandi, M.L.; Falchetti, A.; Tonelli, F.

1993-12-01

Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, the authors had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However,more » the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development. 28 refs., 2 figs.« less

Retrospective evaluation of toceranib phosphate (Palladia) use in cats with mast cell neoplasia.

PubMed

Berger, Erika P; Johannes, Chad M; Post, Gerald S; Rothchild, Gillian; Shiu, Kai-Biu; Wetzel, Sarah; Fox, Leslie E

2018-02-01

Objectives The purpose of this study was to solicit and compile data from practicing veterinary specialists regarding their use of toceranib in cats with mast cell neoplasia and to provide initial assessment of possible clinical benefit and adverse events. Methods The American College of Veterinary Internal Medicine and Oncology listservs were used to solicit data pertaining to cases in which toceranib was used in the treatment of feline mast cell neoplasia. Cases were included if the following data were received: signalment (age, sex, breed), diagnosis of mast cell neoplasia by either cytology or histopathology, anatomic classification of disease (cutaneous, splenic/hepatic, gastrointestinal, other), previous and concurrent treatment, toceranib dose (mg/kg) and schedule, duration of therapy, best response and documentation of adverse events. Results Case data from 50 cats with cutaneous (n = 22), splenic/hepatic (visceral) (n = 10), gastrointestinal (n = 17) or other (n = 1) mast cell neoplasia were received. Clinical benefit was seen in 80% (40/50), including 86% (19/22) with cutaneous, 80% (8/10) with visceral and 76% (13/17) with gastrointestinal involvement. A majority of cats (n = 35) received glucocorticoids during toceranib treatment. Median duration of treatment in cats experiencing clinical benefit was 36 weeks (range 4-106 weeks), 48 weeks (range 12-199 weeks) and 23 weeks (range 13-81 weeks) for cutaneous, visceral and gastrointestinal cases, respectively. Toceranib was administered at a median dose of 2.5 mg/kg (range 1.6-3.5 mg/kg); in 90% (45/50) the drug was given three times per week. Treatment was generally well tolerated with 60% (30/50) of cats experiencing adverse events. The majority of these events were low-grade (grade 1 or 2) gastrointestinal or hematologic events that resolved with treatment break and/or dose adjustment. Conclusions and relevance Toceranib appears to be well tolerated in feline patients with mast cell neoplasia

Combining large area fluorescence with multiphoton microscopy for improved detection of oral epithelial neoplasia (Conference Presentation)

NASA Astrophysics Data System (ADS)

Pal, Rahul; Yang, Jinping; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

2016-03-01

Volumetric Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia representing the complex microstructural organization of mucosa, potentially providing high specificity for detection of neoplasia, but is limited by small imaging area. Large area fluorescence methods on the other hand show high sensitivity appropriate for screening but are hampered by low specificity. In this study, we apply MPAM-SHGM following guidance from large area fluorescence, by either autofluorescence or a targeted metabolic fluorophore, as a potentially clinically viable approach for detection of oral neoplasia. Sites of high neoplastic potentially were identified by large area red/green autofluorescence or by a fluorescently labelled deoxy-glucose analog, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) to highlight areas of high glucose uptake across the buccal pouch of a hamster model for OSCC. Follow-up MPAM-SHGM was conducted on regions of interests (ROIs) to assess whether microscopy would reveal microscopic features associated with neoplasia to confirm or exclude large area fluorescence findings. Parameters for analysis included cytologic metrics, 3D epithelial connective tissue interface metrics (MPAM-SHGM) and intensity of fluorescence (widefield). Imaged sites were biopsied and processed for histology and graded by a pathologist. A small sample of human ex vivo tissues were also imaged. A generalized linear model combining image metrics from large area fluorescence and volumetric MPAM-SHGM indicated the ability to delineate normal and inflammation from neoplasia.

Hybrid capture 2 viral load and the 2-year cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer.

PubMed

Castle, Philip E; Schiffman, Mark; Wheeler, Cosette M

2004-11-01

The purpose of this study was to determine the clinical value of a semiquantitative measure of human papillomavirus viral load by the hybrid capture 2 assay for stratification of the risk of histologic cervical intraepithelial neoplasia grade 3 or carcinoma. The Atypical Cells of Unknown Significance and Low-Grade Squamous Intraepithelial Lesions Triage Study was a randomized clinical trial of 5060 women with 2 years of follow-up to evaluate treatment strategies for women with equivocal or mildly abnormal cervical cytologic condition. The usefulness of the continuous hybrid capture 2 output relative light units/positive controls that were above the positive threshold (1.0 relative light units/positive controls), which was a surrogate for human papillomavirus viral load, for distinguishing between hybrid capture 2 positive women who were diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma during the study from those who were not diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma was examined with the use of receiver-operator characteristic analyses. Relative light units/positive controls values did not further discriminate between hybrid capture 2 positive women with cervical intraepithelial neoplasia grade 3 or carcinoma from those with less than cervical intraepithelial neoplasia grade 3 or carcinoma. The use of a cervical intraepithelial neoplasia grade 2 or more severe or carcinoma case definition did not alter our findings. Among women with atypical cells of unknown significance or low-grade squamous intraepithelial lesion cervical cytologic findings, the hybrid capture 2 viral load measurement did not improve the detection of 2-year cumulative cases of cervical intraepithelial neoplasia grade 3 or carcinoma significantly.

Psychosocial stress and cervical neoplasia risk.

PubMed

Coker, Ann L; Bond, Sharon; Madeleine, Margaret M; Luchok, Kathryn; Pirisi, Lucia

2003-01-01

We assessed the association between psychosocial stress and preinvasive cervical neoplasia development controlling for HR-HPV infection. This case-control study enrolled low-income women receiving family planning services at health department clinics. There were 59 cases with biopsy confirmed HSIL and 163 with low-grade SIL and 160 controls with normal cervical cytology. A modified SLE scale was used to measure stressful events and the perceived impact of the event in the prior 5 years. Unconditional logistic regression was used to assess SIL risk and stressful events scores and by subscales. After adjusting for age, HR-HPV infection, and lifetime number of sex partners, the SLE count score was associated with an increased risk of SIL among white women (aOR = 1.20; 95% CI = 1.04, 1.38) yet not among African American women (aOR = 1.02; 95% CI = 0.87, 1.19). The relationship stress subscale (divorce, infidelity, an increase in the number of arguments, and psychological and physical partner violence) was the only one of four subscales (loss, violence, and financial stress) associated with SIL, again, only among white women (aOR = 1.54; 95% CI = 1.21, 1.96). These data suggest that psychosocial stress may play a role in SIL development. Future studies are needed to confirm these findings, to explore racial difference in reporting stress, and to explore the mechanism through which psychosocial stress may affect cervical neoplasia risk.

GLUT-1 Expression in Pancreatic Neoplasia

PubMed Central

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N. Volkan

2011-01-01

Objectives GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Methods Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. Results There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). Conclusions GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression. PMID:21206329

The role of surgery in the management of gestational trophoblastic neoplasia.

PubMed

Doll, Kemi M; Soper, John T

2013-07-01

Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases.

Esophagectomy for Superficial Esophageal Neoplasia.

PubMed

Watson, Thomas J

2017-07-01

Endoscopic therapies have become the standard of care for most cases of Barrett's esophagus with high-grade dysplasia or intramucosal adenocarcinoma. Despite a rapid and dramatic evolution in treatment paradigms, esophagectomy continues to occupy a place in the therapeutic armamentarium for superficial esophageal neoplasia. The managing physician must remain cognizant of the limitations of endoscopic approaches and consider surgical resection when they are exceeded. Esophagectomy, performed at experienced centers for appropriately selected patients with early-stage disease can be undertaken with the expectation of cure as well as low mortality, acceptable morbidity, and good long-term quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett’s-associated neoplasia

PubMed Central

Thekkek, Nadhi; Lee, Michelle H.; Polydorides, Alexandros D.; Rosen, Daniel G.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2015-01-01

Abstract. Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett’s-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett’s-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett’s esophagus (BE), dysplasia, or esophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope (HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC=0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett’s-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance. PMID:25950645

Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia

PubMed Central

Visser, J; Nijman, H W; Hoogenboom, B-N; Jager, P; van Baarle, D; Schuuring, E; Abdulahad, W; Miedema, F; van der Zee, A G; Daemen, T

2007-01-01

Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-γ/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-γ T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. PMID:17937675

Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer.

PubMed

Palan, Prabhudas R; Woodall, Angela L; Anderson, Patrick S; Mikhail, Magdy S

2004-05-01

alpha-Tocopherol is a potent antioxidant that protects cell membranes against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane alpha-tocopherol concentrations, and altered levels may suggest membrane damage. The objective of this study was to determine the levels of alpha-tocopherol and alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and red blood cells that were obtained from control subjects and patients with cervical intraepithelial neoplasia and cervical cancer. In this cross-sectional study, 72 women, (32 African American and 40 Hispanic) were recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia; 14 women had cervical cancer, and 21 women were considered control subjects, who had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl quinone levels were determined in red blood cell and plasma by high-pressure liquid chromatography. Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively, by Kruskal-Wallis test) in study groups compared with the control group; red blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not altered significantly. The lower alpha-tocopherol level that was observed in this study is consistent with our previous reports of decreased antioxidant concentrations and increased oxidative stress in women with cervical intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha-tocopheryl quinone levels suggest undamaged cell membrane. Further studies are needed to investigate the potential role of oxidative stress in cervical intraepithelial neoplasia.

Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia

PubMed Central

Mandal, Ranajit; Kundu, Pratip; Biswas, Jaydip

2016-01-01

Human papillomavirus (HPV) is a well-established causative agent of malignancy of the female genital tract and a common Sexually Transmitted Infection. The probable co-factors that prevent spontaneous clearance of HPV and progression to neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory conditions can lead to pre-neoplastic manifestations in the cervical epithelium; however their specific role in cervical carcinogenesis is not yet established. Therefore it is imperative to study the likely association between HPV and co-infection with various common pathogens in the genital tract of women having cervical precancer or cancer. A “Pubmed” search was made for articles in Literature on this topic using the words: Cervical neoplasia, HPV, co-infections, Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida, Chlamydia and the relevant information obtained was used to draft the review. PMID:27042571

Intestinal obstruction management in patients with advanced abdominal neoplasia.

PubMed

Simion, L; Straja, Nd; Alecu, M; Poroch, V; Moşoiu, D; Panti, C; Grigorean, V; Brătucu, E

2014-01-01

The present study describes the difficulties encountered in the diagnostic process and treatment of intestinal obstruction developed by patients with advanced abdominal neoplasia. This unicentric and retrospective study evaluates patients suffering from intestinal occlusion operated on at the First Surgical Clinic of the Oncology Institute in Bucharest, over a period of 4 years (2010 - 2013). Of these, 61 cases in which the occlusion occurred on the background of an advanced abdominal neoplasia were selected. We considered as advanced those cases of abdominal cancer where curative oncologic treatment is no longer possible due to the evolution stage. The random selection of the study period, the introduction of all the patients identified with this type of pathology, as well as the concentration of advanced abdominal neoplasia at the Oncology Institute in Bucharest are the elements that allow us to state that the results of this study are representative. Particularities related to the clinical aspects of the intestinal occlusion in these patients, as well as difficulties in establishing the correct diagnosis were encountered.Surgical cure of the occlusion, with palliative aim of course,was possible in only 47 cases (representing 77.05%). A standard treatment course cannot be devised for this type of patients. Palliative care, indispensable in cases of advanced neoplastic disease, remains the sole therapeutic method available for patients with no surgical cure for the obstruction. The main objective, for the entire study lot, was to ensure an as high as possible quality of life,a factor we must bear in mind as often as possible when choosing a surgical solution. Of course, when surgical treatment can be applied, overcoming the occlusive episode prolongs these patients' life and can even allow for other courses of complementary treatment to be undertaken. Celsius.

Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: First in-human results

PubMed Central

Sturm, Matthew B.; Joshi, Bishnu P.; Lu, Shaoying; Piraka, Cyrus; Khondee, Supang; Elmunzer, B. Joseph; Kwon, Richard S.; Beer, David G.; Appelman, Henry; Turgeon, D. Kim; Wang, Thomas D.

2013-01-01

Esophageal adenocarcinoma is rising rapidly in incidence, and usually develops from Barrett’s esophagus, a precursor condition commonly found in patients with chronic acid reflux. Pre-malignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-humans results show that this targeted imaging agent is safe, and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach. PMID:23658246

Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis.

PubMed

Flores, Brisas M; O'Connor, Anthony; Moss, Alan C

2017-12-01

Long-standing ulcerative colitis is an established risk factor for colorectal neoplasia. A number of observational studies have suggested that evidence of mucosal inflammation (endoscopic or histologic) is associated with a greater risk for colorectal neoplasia than is mucosal healing. Our goal was to systematically analyze the risk of colorectal neoplasia in patients with ulcerative colitis who have ongoing mucosal inflammation to better inform surveillance strategies. We performed a systematic review and meta-analysis of the effect of endoscopic and/or histologic inflammation on the risk of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. Six studies met the inclusion criteria, incorporating outcomes in 1443 patients. No study used a single validated measure for mucosal inflammation. The pooled odds ratio for colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those with histologic inflammation, when compared with those with mucosal healing. The overall quality of the studies was good. The presence of objective evidence of mucosal inflammation during follow-up in patients with ulcerative colitis is associated with a greater risk of subsequent colorectal neoplasia than in those with mucosal healing. This risk factor should be considered in guidelines on surveillance intervals for these patients. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Clinicopathologic analysis of 370 cases of vulvar intraepithelial neoplasia. Italian Study Group on Vulvar Disease.

PubMed

1996-09-01

To investigate epidemiologic, clinical and pathologic aspects of various grades of vulvar intraepithelial neoplasia (VIN). A retrospective, multicenter study of 370 cases of vulvar intraepithelial neoplasia (VIN) was performed by the Italian Study Group on Vulvar Disease. Of the 370 cases, 148 were VIN 1 (40.0%, 53 were VIN 2 (14.3%), and 169 were VIN 3 (45.7%). The mean age of the patients was 52.6 years. During the study period an increase in the rate of human papillomavirus-associated VIN was observed. In addition, while VIN 1 and 2 were associated mostly with squamous cell hyperplasia, VIN 3 was almost equally associated with lichen sclerosus and squamous cell hyperplasia; the difference was statistically significant. Intraepithelial or invasive squamous neoplasia of the lower genital tract was associated in 22% of the cases (82/370). The results of the investigation, although not allowing firm conclusions due to the retrospective and multicentered nature of the study, demonstrate the extreme heterogeneity of VIN lesions.

Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias.

PubMed

Suehiro, Yutaka; Hashimoto, Shinichi; Higaki, Shingo; Fujii, Ikuei; Suzuki, Chieko; Hoshida, Tomomi; Matsumoto, Toshihiko; Yamaoka, Yuko; Takami, Taro; Sakaida, Isao; Yamasaki, Takahiro

2018-03-30

Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia. This study comprised 113 patients with colorectal neoplasia and 25 control individuals. For the new methylation assay, DNA was treated in two stages with methylation-sensitive restriction enzymes, followed by measurement of copy numbers of hTERT and methylated TWIST1 by multiplex droplet digital PCR. The fecal immunochemical test had a sensitivity of 8.0% for non-advanced adenoma, 24.3% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 88.0%. The new assay had a sensitivity of 36.0% for non-advanced adenoma, 30.0% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 92.0%. Combination of the both tests increased the sensitivity to 40.0%, 45.7%, and 72.2% for the detection of non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively, and resulted in a specificity of 84.0%. Combination of both tests may provide an alternative screening strategy for colorectal neoplasia including potentially precancerous lesions and colorectal cancer.

A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma

PubMed Central

Léonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stéphanie; Doyen, Jean; Delvenne, Philippe

2014-01-01

Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases. PMID:24719870

Can gallbladder polyps predict colorectal adenoma or even neoplasia? A systematic review.

PubMed

Stergios, Konstantinos; Damaskos, Christos; Frountzas, Maximos; Nikiteas, Nikolaos; Lalude, Olutunde

2016-09-01

The purpose of the present systematic review is to identify whether an association between gallbladder polyps and colorectal adenoma or neoplasia exists. We conducted a systematic review searching the Medline (1966-2016), Scopus (2004-2016), ClinicalTrials.gov (2008-2016) and Cochrane Central Register of Controlled Trials CENTRAL (1999-2016) databases together with reference lists from included studies. All prospective and retrospective observational cohort studies were included. Four studies were finally included which included 17,437 patients. The association between gallbladder polyps and colorectal adenoma or even neoplasia is not unanimously supported. However, a possible association is clearly depicted. According to one study it seems that this correlation seems to become significant only when the gallbladder polyps exceed the size of 5 mm. However, the impact of size of gallbladder polyps was not investigated in the remaining studies. According to the results of our systematic review there is some evidence to support the hypothesis that gallbladder polyps might adequately predict future risk of colorectal neoplasia. At present, however, current knowledge is very limited and the available data scarce. In this context further studies are necessary to be carried out, before the presence of gallbladder polyps on ultrasound can be recommended as an indication to perform a screening colonoscopy on the same patient. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy.

PubMed

Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad; Oosterhuis, J Wolter; Rajpert-De Meyts, Ewa; Ulbright, Thomas M; Skakkebaek, Niels E

2016-07-01

The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce the reasoning for uniting behind a new name, endorsed unanimously at the World Health Organization (WHO) consensus classification 2016: germ cell neoplasia in situ (GCNIS). © 2016 John Wiley & Sons Ltd.

Endometrial neoplasia in reproductive-aged Thai women with polycystic ovary syndrome.

PubMed

Indhavivadhana, Suchada; Rattanachaiyanont, Manee; Wongwananuruk, Thanyarat; Techatraisak, Kitirat; Rayasawath, Nana; Dangrat, Chongdee

2018-05-09

To determine the risk of endometrial neoplasia in relation to endometrial thickness and to evaluate factors influencing endometrial thickness in reproductive-aged Thai women with polycystic ovary syndrome (PCOS). The present cross-sectional study was done at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, between October 1, 2010, and January 31, 2013. We recruited women (aged ≥18 years) with PCOS diagnosed according to the revised 2003 Rotterdam criteria. Data were collected for physical examinations, pelvic ultrasonography, hormonal profiles, and carbohydrate metabolic profiles. Endometrial tissue was obtained using a disposable endometrial-suctioning device. The final analysis included 122 women. Six (4.9%) patients had endometrial neoplasia. All six women had an endometrial thickness of 7 mm or more, representing a risk of 8.7% (6/69) in this group. The endometrial thickness was significantly but weakly associated with body mass index (r=0.227, P=0.012), 2-hour blood glucose (r=0.323, P=0.001), fasting glucose to insulin ratio (r=0.185, P=0.042), homeostatic model assessment of insulin resistance (r=0.183, P=0.044), and free testosterone (r=0.236, P=0.009). No categorical risk factors for an endometrial thickness of 7 mm or more were identified. Thai women with PCOS and a thick endometrium (≥7 mm) had an 8.7% risk of endometrial neoplasia. Invasive endometrial surveillance for the prevention of endometrial cancer is recommended in these women. © 2018 International Federation of Gynecology and Obstetrics.

'Feeling someone is there for you' - experiences of women with vulvar neoplasia with care delivered by an Advanced Practice Nurse.

PubMed

Kobleder, Andrea; Mayer, Hanna; Senn, Beate

2017-02-01

To explore the experiences of women with vulvar neoplasia with care delivered by an Advanced Practice Nurse. Women with vulvar neoplasia suffer from a high number of symptoms and report a lack of information and support by health care professionals. Further, talking about their disease, which is still a social taboo, is difficult for them. From approaches for other patients, it can be suggested that support from an Advanced Practice Nurse can be helpful. For Advanced Practice Nurse development, implementation and evaluation, it is important to assess patients' perceptions. But so far, little is known about how patients with vulvar neoplasia experience support of an Advanced Practice Nurse. A qualitative interview study was chosen to gain understanding of the experience of women with vulvar neoplasia who received care delivered by an Advanced Practice Nurse. Narrative interviews were conducted with a purposive sample of 13 women with vulvar neoplasia after they received care from an Advanced Practice Nurse for six months. Thematic analysis was used to analyse the data from the interviews. Four main themes could be identified: a trusting relationship; accessibility; feeling safe and secure; and feeling someone is there for you. Women felt more secure and less alone in the experience of their illness through having the possibility of contacting an Advanced Practice Nurse and getting sufficient information and psychosocial support. Women with vulvar neoplasia experienced care delivered by an Advanced Practice Nurse as 'feeling someone is there for you'. Due to the localisation of the disease and the associated social taboo, psychosocial support from the Advanced Practice Nurse beyond months after surgery was very important for them. Addressing psychosocial needs in caring for women with vulvar neoplasia must be given greater attention in clinical practice. Further, continuous nursing support delivered by an Advanced Practice Nurse beyond the acute treatment phase can

Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

PubMed

Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

2014-01-01

Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Cytologically diagnosed Gardnerella vaginalis infection and cervical (pre)neoplasia as established in population-based cervical screening.

PubMed

Klomp, Johanna M; Boon, Mathilde E; Van Haaften, Maarten; Heintz, A Peter M

2008-11-01

Cervical inflammation has been proposed as a cofactor in the development of cervical cancer. The purpose of this study was to document the prevalence of cervical (pre)neoplastic changes in asymptomatic women with a cytologically diagnosed Gardnerella vaginalis infection. Data were collected from 800,498 Dutch asymptomatic women, participating in the Dutch national screening program. Prevalences of (pre)neoplasia were calculated for G vaginalis smears using a healthy flora as reference. The prevalence of G vaginalis infection was 0.6 per thousand. The odds ratio for (pre)neoplasia was significantly higher in smears with G vaginalis infection compared with smears of women with a healthy vaginal flora (odds ratio, 10.3; 95% confidence interval, 6.6-16.1). Cytologically diagnosed G vaginalis smears show a strong covariation with the presence of cervical (pre)neoplasia. Future research should therefore focus on the exact causal relation between cytologic G vaginalis infection and the presence of (pre)neoplastic changes of the cervix.

[Hysterectomy and intraepithelial neoplasia of the lower female genital tract].

PubMed

Spuhler, S; De Grandi, P

1992-01-01

Delimiting the place of hysterectomy in cases of lower genital tract intraepithelial neoplasias in women. The laser and colposcopy centre (CCL) of a maternity unit in Lausanne in the Vaudois University Hospital Centre (CHUV). THE TYPE OF STUDY: Retrospective on 1,303 patients between 1986 and 1990. THE SUBJECTS AND TREATMENT: 853 cases of cervical intraepithelial neoplasia (CIN) and 79 cases of vaginal intraepithelial neoplasia (VAIN) were treated with CO2 laser. The situations in which hysterectomy could be considered in the course of treatment are discussed. They are: 1) Dysplasia persisting after treatment, 2) when pathological tissue is found on examining slides from conisation specimens, 3) micro-invasive carcinoma, 4) post-operative obstructive stenosis. The multiple location of dysplasia lesions of the lower genital tract was calculated for all the patients examined. It shows that hysterectomy itself will be insufficient to remove all dysplasias since frequently (9.2%) of lesions are found in the vagina in cases that have dysplasia of the cervix. Residual lesions after hysterectomy are shown up by VAIN which are responsible for the persistence of changes in the control smears (in which there were 9 cases of VAIN3 after hysterectomy in this series). Treatment therefore is hazardous and only poorly successful because the site of these lesions is often hidden in the scar through the top of the vagina. Furthermore their discovery in uncertain since there is a tendency at present to avoid out cytological screening of these patients once they have undergone hysterectomy. The high incidence of multifocal lesions and the possibility that is very real of residual dysplasia after hysterectomy has made the authors limit the place of hysterectomy in these cases, preferring to use conservative treatments and emphasizing the need to continue cytological controls for after treatment.

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

PubMed

Tinmouth, Jill; Peeva, Valentina; Amare, Henok; Blitz, Sandra; Raboud, Janet; Sano, Marie; Steele, Leah; Salit, Irving E

2016-09-01

High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. This was a prospective cohort study. The study was conducted at an outpatient clinic at a tertiary care center in Toronto. Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. We measured the incidence of anal cancer per 100 person-years of follow-up. Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borowsky, A D; Dingley, K; Ubick, E

2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIPmore » showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.« less

Human Papilloma Virus Identification in Breast Cancer Patients with Previous Cervical Neoplasia.

PubMed

Lawson, James S; Glenn, Wendy K; Salyakina, Daria; Clay, Rosemary; Delprado, Warick; Cheerala, Bharathi; Tran, Dinh D; Ngan, Christopher C; Miyauchi, Shingo; Karim, Martha; Antonsson, Annika; Whitaker, Noel J

2015-01-01

Women with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active. A range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. The same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001). These findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

PDX-1 Is a Therapeutic Target for Pancreatic Cancer, Insulinoma and Islet Neoplasia Using a Novel RNA Interference Platform

PubMed Central

Liu, Shi-He; Rao, Donald D.; Nemunaitis, John; Senzer, Neil; Zhou, Guisheng; Dawson, David; Gingras, Marie-Claude; Wang, Zhaohui; Gibbs, Richard; Norman, Michael; Templeton, Nancy S.; DeMayo, Francesco J.; O'Malley, Bert; Sanchez, Robbi; Fisher, William E.; Brunicardi, F. Charles

2012-01-01

Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pancreatic and islet neoplasia specimens revealed marked PDX-1 overexpression, suggesting PDX-1 as a “drugable” target within these diseases. To do so, a novel RNA interference effector platform, bifunctional shRNAPDX-1, was developed and studied in mouse and human cell lines as well as in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Systemic delivery of bi-shRNAhumanPDX-1 lipoplexes resulted in marked reduction of tumor volume and improved survival in a human pancreatic cancer xenograft mouse model. bi-shRNAmousePDX-1 lipoplexes prevented death from hyperinsulinemia and hypoglycemia in an insulinoma mouse model. shRNAmousePDX-1 lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of islet neoplasia. PDX-1 was overexpressed in pancreatic neuroendocrine tumors and nesidioblastosis. These data demonstrate that PDX-1 RNAi therapy controls hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia, therefore, PDX-1 is a potential therapeutic target for these pancreatic diseases. PMID:22905092

5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis

PubMed Central

Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui

2014-01-01

Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited. PMID:24710620

5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

PubMed

Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui

2014-01-01

Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

Immune response modifiers and cutaneous neoplasia.

PubMed

Spencer, James M

2002-12-01

The incidence of skin cancer exceeds that of all other cancers combined, and the trend is increasing. Around 1.2 million new cases of skin cancer are seen annually in the United States alone. The 3 major types of skin cancer commonly seen, in frequency of occurrence, include basal cell carcinoma, squamous cell carcinoma, and melanoma. All are thought to arise from cells in the epidermis, and all are most often induced by exposure to ultraviolet radiation. There is a relatively low mortality rate from cutaneous neoplasia--approximately 10,000 per year--with the majority of deaths due to malignant melanoma. However, there is a significant morbidity from these tumors, making skin cancer a major public health problem.

Evaluation of intracranial neoplasia and noninfectious meningoencephalitis in dogs by use of short echo time, single voxel proton magnetic resonance spectroscopy at 3.0 Tesla.

PubMed

Carrera, Inés; Richter, Henning; Beckmann, Katrin; Meier, Dieter; Dennler, Matthias; Kircher, Patrick R

2016-05-01

OBJECTIVE To investigate metabolite concentrations of the brains of dogs with intracranial neoplasia or noninfectious meningoencephalitis by use of short echo time, single voxel proton magnetic resonance spectroscopy ((1)H MRS) at 3.0 T. ANIMALS 29 dogs with intracranial lesions (14 with neoplasia [3 oligodendromas, 3 glioblastomas multiformes, 3 astrocytomas, 2 lymphomas, and 3 meningiomas] and 15 is with noninfectious meningoencephalitis) and 10 healthy control dogs. PROCEDURES Short echo time, single voxel (1)H-MRS at 3.0 T was performed on neoplastic and noninfectious inflammatory intracranial lesions identified with conventional MRI. Metabolites of interest included N-acetyl aspartate (NAA), total choline, creatine, myoinositol, the glutamine-glutamate complex (Glx), glutathione, taurine, lactate, and lipids. Data were analyzed with postprocessing fitting algorithm software. Metabolite concentrations relative to brain water content were calculated and compared with results for the healthy control dogs, which had been previously evaluated with the same (1)H MRS technique. RESULTS NAA, creatine, and Glx concentrations were reduced in the brains of dogs with neoplasia and noninfectious meningoencephalitis, whereas choline concentration was increased. Concentrations of these metabolites differed significantly between dogs with neoplasia and dogs with noninfectious meningoencephalitis. Concentrations of NAA, creatine, and Glx were significantly lower in dogs with neoplasia, whereas the concentration of choline was significantly higher in dogs with neoplasia. Lipids were predominantly found in dogs with high-grade intra-axial neoplasia, meningioma, and necrotizing meningoencephalitis. A high concentration of taurine was found in 10 of 15 dogs with noninfectious meningoencephalitis. CONCLUSIONS AND CLINICAL RELEVANCE (1)H MRS provided additional metabolic information about intracranial neoplasia and noninfectious meningoencephalitis in dogs.

[Detection of early neoplasia in Barrett's oesophagus: focus attention on index endoscopy in short-segment-Barrett's oesophagus with random biopsies].

PubMed

Behrens, A; Pech, O; Wuthnow, E; Manner, H; Pohl, J; May, A; Ell, C

2015-06-01

Detecting early neoplasias in Barrett's oesophagus (BE) is challenging. Recent publications have been focusing on improving the detection of such lesions during Barrett's surveillance. However in a recently published Danish register study calculating the risk for cancer-development in BE two-thirds of the diagnosed tumors were identified during the first examination or in the first year. This means that index endoscopy might be more effective than surveillance in detecting early neoplasia in BE.  In the period from January 2010 to April 2011, all patients who consecutively presented with a diagnosis of early neoplastic changes in BE were recorded prospectively. The analysis included data for 121 patients. In patients with short-segment BE (SSBE), neoplasia was only diagnosed in 6 % of cases in the surveillance examination, compared with 44 % of cases in long-segment BE (LSBE). The neoplastic lesion was identified visually in 43 patients (36 %) during the external EGD. Type II tumours were detected in 40 % (39/98) and were correctly assessed as neoplastic in 25 % of cases (24/98). 1. in patients with SSBE almost all early tumours are diagnosed by index endoscopy and not by Barrett's surveillance; 2. around 40 % of all early neoplasias are endoscopically invisible and are only diagnosed using four-quadrant biopsies; 3. the macroscopic tumour type has a substantial influence on the detection rate for neoplasia. If efforts to increase the detection rate for early neoplasia in BE are focused solely on the Barrett's surveillance method, then only a minority of patients - 20 % in the present group - will benefit from the measure. German clinical trials register, DRKS00 004 168. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome.

PubMed

Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka; Macrae, Finlay; Möslein, Gabriela; Olschwang, Sylviane; Bisgaard, Marie-Luise; Ramesar, Raj; Eccles, Diana; Maher, Eamonn R; Bertario, Lucio; Jarvinen, Heikki J; Lindblom, Annika; Evans, D Gareth; Lubinski, Jan; Morrison, Patrick J; Ho, Judy W C; Vasen, Hans F A; Side, Lucy; Thomas, Huw J W; Scott, Rodney J; Dunlop, Malcolm; Barker, Gail; Elliott, Faye; Jass, Jeremy R; Fodde, Ricardo; Lynch, Henry T; Mathers, John C

2008-12-11

Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome. Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.) 2008 Massachusetts Medical Society

Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

PubMed

Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

2017-06-01

Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

Four Cases of Spontaneous Neoplasia in the Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species.

PubMed

Taylor, Kyle R; Milone, Nicholas A; Rodriguez, Carlos E

2017-01-01

The naked mole-rat (Heterocephalus glaber) is widely acclaimed to be cancer-resistant and of considerable research interest based on a paucity of reports of neoplasia in this species. We have, however, encountered four spontaneous cases of neoplasia and one presumptive case of neoplasia through routine necropsy and biopsy of individuals in a zoo collection of nonhybrid naked mole-rats bred from a single pair. One case each of metastasizing hepatocellular carcinoma, nephroblastoma (Wilms' tumor), and multicentric lymphosarcoma, as well as presumptive esophageal adenocarcinoma (Barrett's esophagus-like) was identified postmortem among 37 nonautolyzed necropsy submissions of naked mole-rats over 1-year-old that were submitted for necropsy between 1998 and August 2015. One incidental case of cutaneous hemangioma was also identified antemortem by skin biopsy from one naked mole-rat examined for trauma. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Financial burden is associated with worse health-related quality of life in adults with multiple endocrine neoplasia type 1.

PubMed

Peipert, Benjamin J; Goswami, Sneha; Helenowski, Irene; Yount, Susan E; Sturgeon, Cord

2017-12-01

Health-related quality of life and financial burden among patients with multiple endocrine neoplasia type 1 is poorly described. It is not known how financial burden influences health-related quality of life in this population. We hypothesized that the financial burden attributable to multiple endocrine neoplasia type 1 is associated with worse health-related quality of life. United States adults (≥18 years) with multiple endocrine neoplasia type 1 were recruited from the AMENSupport MEN online support group. Patient demographics, clinical characteristics, and financial burden were assessed via an online survey. The instrument Patient-Reported Outcomes Measurement Information System 29-item profile measure was used to assess health-related quality of life. Multivariable linear regression was used to identify significant variables in each Patient-Reported Outcomes Measurement Information System domain. Out of 1,378 members in AMENSupport, our survey link was accessed 449 times (33%). Of 153 US respondents who completed our survey, 84% reported financial burden attributable to multiple endocrine neoplasia type 1. The degree of financial burden had a linear relationship with worse health-related quality of life across all Patient-Reported Outcomes Measurement Information System domains (r = 0.36-0.55, P < .001); 63% reported experiencing ≥1 negative financial event(s). Borrowing money from friends/family (30%), unemployment (13%), and spending >$100/month out-of-pocket on prescription medications (46%) were associated consistently with impaired health-related quality of life (ß = 3.75-6.77, P < .05). Respondents were 3- and 34-times more likely to be unemployed and declare bankruptcy than the US population, respectively. This study characterizes the financial burden in patients with multiple endocrine neoplasia type 1. Individuals with multiple endocrine neoplasia type 1 report a high degree of financial burden, negative financial events, and

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy.

PubMed

Jastreboff, A M; Cymet, T

2002-04-01

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed.

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

PubMed Central

Jastreboff, A; Cymet, T

2002-01-01

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed. PMID:11930025

Surgical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial

Microtopographic Inspection and Fractal Analysis of Skin Neoplasia

NASA Astrophysics Data System (ADS)

Costa, Manuel F. M.; Hipolito, Alberto Valencia; Gutierrez, Gustavo Fidel; Chanona, Jorge; Gallegos, Eva Ramón

2008-04-01

) corresponding to some neoplasia is higher (1.334+/-0.072) than those for healthy skin (1.091+/-0.082). A significant difference between the fractal dimensions of neoplasia and healhty skin (>0.001) was registered. The FD of microtopography maps (FDm) can also distinguish between healthy and malignant tissue in general (2.277+/-0.070 to 2.309+/-0.040), but not discriminate the different types of skin neoplasias. The combination of the rugometric evaluation and fractal geometry characterization provides valuable information about the malignity of skin lesions and type of lesion.

[Treatment of cervical intraepithelial neoplasia using the CO2 laser].

PubMed

Trejo Solorzano, O; González Iñiguez, R

1991-04-01

The use of laser therapy in CIN, is a practical method that has revolutionized the treatment of a very common pathology, that is the cervical neoplasia in its early stages. 86 patients with different stages of cervical intraepithelial neoplasia, were studied. Patients in groups I (45 patients) y II (28 patients), were submitted to a vaporization crater of the whole transformation zone because of having the cervical canal free of lesion. In group III (13 patients), a cylinder of the cervix was done to perform histological study, whether the cervical canal was compromised or not. The cytology control results for group I were excellent; from (45 patients) who came to 3-month check-up 79.1% of the whole presented negative II. For group II (28 patients), in first pap smear two patients (7.1%) had CIN, the rest of smears were reported 66% negative II, and in the 30.6% negative I. For the group III 14.2% (5 patients) of the whole had abnormal results, the rest of the smears 73.5% of the results reported negative II. The incidence of failure for this procedure is similar to that of hysterectomy with the same therapeutic goal .

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

Skinning vulvectomy for the treatment of vulvar intraepithelial neoplasia 2-3: a study of 21 cases.

PubMed

Ayhan, A; Tuncer, Z S; Doğan, L; Yüce, K; Küçükali, T

1998-01-01

Twenty-one cases of patients with vulvar intraepithelial neoplasia (VIN) 2-3 were reviewed. The mean age at diagnosis was 45.4 years. All of the patients presented with vulvar pruritus. Five of the patients had hypertension, two had coronary heart disease and two had diabetes mellitus as complicating medical illnesses. None of the patients had history or evidence of vaginal intraepithelial neoplasia (VAIN) or cervical intraepithelial neoplasia (CIN), and only one patient had invasive cervical cancer at diagnosis. Provided the histology confirmed VIN, the patients were subjected to a skinning vulvectomy procedure. Of the patients, 15 (71.4%) had VIN 2, and the remaining 6 (28.6%) had VIN 3 at preoperative evaluation. Histologic analysis of skinning vulvectomy specimens revealed no evidence of neoplasia in three patients (14.2%). Multifocality was observed in only three patients (14.2%). The areas involved were the perineum in four patients, labia in 15 and clitoris in two patients. Associated vulvar pathologies were condyloma acuminata in one, squamous vulvar hyperplasia in three and lichen sclerosus with squamous hyperplasia in one patient. The complications of the procedure included febrile morbidity in three patients and minor wound break-down in one patient. None of the patients in this series experienced recurrence. Skinning vulvectomy seems to have a high success rate in treatment of VIN 2-3 with minimal postoperative complications and satisfactory cosmetic results. However, observation of only three patients with multifocal lesions as well as no patient with invasive cancer adds credence to an ablative procedure after appropriate evaluation under colposcopy.

Single-session endoscopic resection and focal radiofrequency ablation for short-segment Barrett's esophagus with early neoplasia.

PubMed

Barret, Maximilien; Belghazi, Kamar; Weusten, Bas L A M; Bergman, Jacques J G H M; Pouw, Roos E

2016-07-01

The management of early neoplasia in Barrett's esophagus (BE) requires endoscopic resection of visible lesions, followed by radiofrequency ablation (RFA) of the remaining BE. We evaluated the safety and efficacy of combining endoscopic resection and focal RFA in a single endoscopic session in patients with early BE neoplasia. This was a retrospective analysis of patients with early BE neoplasia and a visible lesion undergoing combined endoscopic resection and focal RFA in a single session. Consecutive ablation procedures were performed every 8 to 12 weeks until complete endoscopic and histologic eradication of dysplasia and intestinal metaplasia were reached. Forty patients were enrolled, with a median C1M2 BE segment, a visible lesion with a median diameter of 15 mm, and invasive carcinoma in 68% of cases. Endoscopic resection was performed by using the multiband mucosectomy technique in 80% of cases, and the Barrx(90) catheter (Barrx Medical, Sunnyvale, Calif) was used for focal ablation. When an intention-to-treat analysis was used, both complete remission of all neoplasia and intestinal metaplasia were 95% after a median follow-up of 19 months. Stenoses occurred in 33% of cases and were successfully managed with a median number of 2 dilations. In 43% of patients, 1 single-session treatment resulted in complete histologic remission of intestinal metaplasia. Combining endoscopic resection and focal RFA in a single session appears to be effective. Less-aggressive RFA regimens could limit the adverse event rates. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

PubMed Central

Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin

2013-01-01

Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary. PMID:23875073

Identifying constituent spectra sources in multispectral images to quantify and locate cervical neoplasia

NASA Astrophysics Data System (ADS)

Baker, Kevin C.; Bambot, Shabbir

2011-02-01

Optical spectroscopy has been shown to be an effective method for detecting neoplasia. Guided Therapeutics has developed LightTouch, a non invasive device that uses a combination of reflectance and fluorescence spectroscopy for identifying early cancer of the human cervix. The combination of the multispectral information from the two spectroscopic modalities has been shown to be an effective method to screen for cervical cancer. There has however been a relative paucity of work in identifying the individual spectral components that contribute to the measured fluorescence and reflectance spectra. This work aims to identify the constituent source spectra and their concentrations. We used non-negative matrix factorization (NNMF) numerical methods to decompose the mixed multispectral data into the constituent spectra and their corresponding concentrations. NNMF is an iterative approach that factorizes the measured data into non-negative factors. The factors are chosen to minimize the root-mean-squared residual error. NNMF has shown promise for feature extraction and identification in the fields of text mining and spectral data analysis. Since both the constituent source spectra and their corresponding concentrations are assumed to be non-negative by nature NNMF is a reasonable approach to deconvolve the measured multispectral data. Supervised learning methods were then used to determine which of the constituent spectra sources best predict the amount of neoplasia. The constituent spectra sources found to best predict neoplasia were then compared with spectra of known biological chromophores.

Thyroid neoplasia risk is increased nearly 30 years after the Chernobyl accident.

PubMed

Tronko, Mykola; Brenner, Alina V; Bogdanova, Tetiana; Shpak, Victor; Oliynyk, Valeriy; Cahoon, Elizabeth K; Drozdovitch, Vladimir; Little, Mark P; Tereshchenko, Valeriy; Zamotayeva, Galyna; Terekhova, Galyna; Zurnadzhi, Lyudmila; Hatch, Maureen; Mabuchi, Kiyohiko

2017-10-15

To evaluate risk of thyroid neoplasia nearly 30 years following exposure to radioactive iodine (I-131) from the 1986 Chernobyl nuclear accident, we conducted a fifth cycle of thyroid screening of the Ukrainian-American cohort during 2012-2015, following four previous screening cycles started in 1998. We identified 47 thyroid cancers (TC) and 33 follicular adenomas (FA) among 10,073 individuals who were <18 years at the time of the accident and had a mean I-131 dose of 0.62 Gy. We found a significant I-131 dose response for both TC and FA, with an excess odd ratio per Gy of 1.36 (95% CI: 0.39-4.15) and 2.03 (95% CI: 0.55-6.69), respectively. The excess risk of malignant and benign thyroid neoplasia persists nearly three decades after exposure and underscores the importance of continued follow-up of this cohort to characterize long-term pattern of I-131 risk. © 2017 UICC.

Elevated serum gastrin is associated with a history of advanced neoplasia in Barrett's esophagus.

PubMed

Wang, Judy S; Varro, Andrea; Lightdale, Charles J; Lertkowit, Nantaporn; Slack, Kristen N; Fingerhood, Michael L; Tsai, Wei Yann; Wang, Timothy C; Abrams, Julian A

2010-05-01

Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett's esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. A total of 95 patients were enrolled. The mean age was 64.7 (+/-10.0) years, and 70.5% were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P=0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95% confidence interval (CI): 1.20-24.8). In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies.

PubMed

Zheng, Han-Han; Jiang, Xue-Liang

2016-04-01

Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal

Distribution of haemic neoplasia of soft-shelled clams in Prince Edward Island: an examination of anthropogenic factors and effects of experimental fungicide exposure.

PubMed

Mateo, D R; MacCallum, G S; McGladdery, S E; Davidson, J

2016-05-01

Haemic neoplasia was first considered a disease of concern for soft-shell clams in Prince Edward Island (PEI) when it was diagnosed as the cause of mass mortalities in 1999. The aetiology of the disease remains elusive, but has been associated with environmental degradation. In this study, a 2-year (2001-2002) geographic and seasonal survey was conducted for haemic neoplasia, using histology, in soft-shell clams from PEI. In addition, using geographic information system, the association between anthropogenic factors in the watersheds at sites affected by haemic neoplasia and the prevalence of the disease was investigated. Finally, histopathological changes were assessed in soft-shell clams experimentally exposed to four concentrations of chlorothalonil for 27 days. Haemic neoplasia could not be induced at any concentration of chlorothalonil. Clams exposed to a concentration of 1000 μg L(-1) of the fungicide, however, exhibited an LC50 of 17 days. Although this information provides additional toxicity information (LC50) for soft-shell clams, further experiments are required to assess longer term exposure to the fungicide. The highest prevalences of haemic neoplasia in PEI were found in North River and Miscouche (28.3-50.9% and 33.0-77.8%, respectively). No clear seasonal patterns were found. There was a correlation between haemic neoplasia prevalence and watersheds with a high percentage of potato acreage and forest coverage (P = 0.026 and P = 0.045, respectively), suggesting a link between anthropogenic activity and the prevalence of the disease. © 2015 John Wiley & Sons Ltd.

Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

PubMed

Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

2009-05-01

A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

The Importance of High-Risk Human Papillomavirus Types Other Than 16 and 18 in Cervical Neoplasia.

PubMed

Robadi, Ibrahim A; Pharaon, Majed; Ducatman, Barbara S

2018-06-01

- Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections. - To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings. - The study comprised a review of the literature. - Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types.

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

PubMed Central

Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

2016-01-01

Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes chrysolophus ) Through Use of Computed Tomography.

PubMed

Woodhouse, Sarah J; Rose, Michelle; Desjardins, Danielle R; Agnew, Dalen W

2015-03-01

A 25-year-old female macaroni penguin (Eudyptes chrysolophus) was diagnosed with exophthalmos secondary to retrobulbar neoplasia through use of computed tomography (CT). Histopathologic examination of the mass supported a diagnosis of malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to determine cell origin; the neoplastic cells did not label with T-cell marker CD3 or B-cell marker BLA.36 and could not be further characterized. The scleral ossicles precluded evaluation of the retrobulbar space by ultrasonography; therefore, CT scanning is recommended for examination of intraorbital structures in penguin and other avian species.

Chemoresistant Gestational Trophoblastic Neoplasia: A Case Report

PubMed Central

M, Sahana

2014-01-01

Gestational trophoblastic neoplasia (GTN) is a disease of women in reproductive age. It is one of the most chemotherapy responsive and highly curable cancer. It is diagnosed when there is clinical, radiologic, pathologic, and/or hormonal evidence of persistent or relapsed gestational trophoblastic disease. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a rare case of chemoresistant GTN which was confirmed to be placental-site trophoblastic tumour (PSTT) on biopsy. PMID:25177610

Folate-genetics and colorectal neoplasia: What we know and need to know next

USDA-ARS?s Scientific Manuscript database

The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTH...

Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy--A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee.

PubMed

Raman, Sripriya; Grimberg, Adda; Waguespack, Steven G; Miller, Bradley S; Sklar, Charles A; Meacham, Lillian R; Patterson, Briana C

2015-06-01

GH and IGF-1 have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during treatment or after treatment is completed. A PubMed search conducted through February 2014 retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications. In children without prior cancer or known risk factors for developing cancer, the clinical evidence does not affirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase the risk for neoplasia in this population, although most of these data are derived from postmarketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence but may increase their risk for subsequent primary neoplasms. In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to the development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH-deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms.

Arf Suppresses Hepatic Vascular Neoplasia in a Carcinogen-Exposed Murine Model

PubMed Central

Busch, Stephanie E; Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

2013-01-01

Hepatic haemangiosarcoma is a deadly malignancy whose aetiology remains poorly understood. Inactivation of the CDKN2A locus, which houses the ARF and p16INK4a tumour suppressor genes, is a common event in haemangiosarcoma patients, but the precise role of ARF in vascular tumourigenesis is unknown. To determine the extent to which ARF suppresses vascular neoplasia, we examined the incidence of hepatic vascular lesions in Arf-deficient mice exposed to the carcinogen urethane (i.p. 1 mg/g). Loss of Arf resulted in elevated morbidity and increased the incidence of both haemangiomas and incipient haemangiosarcomas. Suppression of vascular lesion development by ARF was heavily dependent on both Arf gene-dosage and the genetic strain of the mouse. Trp53-deficient mice also developed hepatic vascular lesions after exposure to urethane, suggesting that ARF signals through a p53-dependent pathway to inhibit the development of hepatic haemangiosarcoma. Our findings provide strong evidence that inactivation of Arf is a causative event in vascular neoplasia and suggest that the ARF pathway may be a novel molecular target for therapeutic intervention in haemangiosarcoma patients. PMID:22430984

2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia.

PubMed

Wood, Brent L; Arroz, Maria; Barnett, David; DiGiuseppe, Joseph; Greig, Bruce; Kussick, Steven J; Oldaker, Teri; Shenkin, Mark; Stone, Elizabeth; Wallace, Paul

2007-01-01

Immunophenotyping by flow cytometry has become standard practice in the evaluation and monitoring of patients with hematopoietic neoplasia. However, despite its widespread use, considerable variability continues to exist in the reagents used for evaluation and the format in which results are reported. As part of the 2006 Bethesda Consensus conference, a committee was formed to attempt to define a consensus set of reagents suitable for general use in the diagnosis and monitoring of hematopoietic neoplasms. The committee included laboratory professionals from private, public, and university hospitals as well as large reference laboratories that routinely operate clinical flow cytometry laboratories with an emphasis on lymphoma and leukemia immunophenotyping. A survey of participants successfully identified the cell lineage(s) to be evaluated for each of a variety of specific medical indications and defined a set of consensus reagents suitable for the initial evaluation of each cell lineage. Elements to be included in the reporting of clinical flow cytometric results for leukemia and lymphoma evaluation were also refined and are comprehensively listed. The 2006 Bethesda Consensus conference represents the first successful attempt to define a set of consensus reagents suitable for the initial evaluation of hematopoietic neoplasia. Copyright 2007 Clinical Cytometry Society.

Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy—A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee

PubMed Central

Grimberg, Adda; Waguespack, Steven G.; Miller, Bradley S.; Sklar, Charles A.; Meacham, Lillian R.; Patterson, Briana C.

2015-01-01

Context: GH and IGF-1 have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during treatment or after treatment is completed. Evidence Acquisition: A PubMed search conducted through February 2014 retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications. Evidence Synthesis: In children without prior cancer or known risk factors for developing cancer, the clinical evidence does not affirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase the risk for neoplasia in this population, although most of these data are derived from postmarketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence but may increase their risk for subsequent primary neoplasms. Conclusions: In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to the development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH-deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms. PMID:25839904

Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women.

PubMed

Robison, Katina; Cronin, Beth; Bregar, Amy; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa

2015-12-01

To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (P<.001). Among women who underwent anoscopy, no anal dysplasia was detected in the low-risk group, whereas 13.4% in the high-risk group had anal dysplasia with 4.2% having anal intraepithelial neoplasia 2 or greater (P<.001). Human immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. II.

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

PubMed

Castinetti, Frederic; Qi, Xiao-Ping; Walz, Martin K; Maia, Ana Luiza; Sansó, Gabriela; Peczkowska, Mariola; Hasse-Lazar, Kornelia; Links, Thera P; Dvorakova, Sarka; Toledo, Rodrigo A; Mian, Caterina; Bugalho, Maria Joao; Wohllk, Nelson; Kollyukh, Oleg; Canu, Letizia; Loli, Paola; Bergmann, Simona R; Biarnes Costa, Josefina; Makay, Ozer; Patocs, Attila; Pfeifer, Marija; Shah, Nalini S; Cuny, Thomas; Brauckhoff, Michael; Bausch, Birke; von Dobschuetz, Ernst; Letizia, Claudio; Barczynski, Marcin; Alevizaki, Maria K; Czetwertynska, Malgorzata; Ugurlu, M Umit; Valk, Gerlof; Plukker, John T M; Sartorato, Paola; Siqueira, Debora R; Barontini, Marta; Szperl, Malgorzata; Jarzab, Barbara; Verbeek, Hans H G; Zelinka, Tomas; Vlcek, Petr; Toledo, Sergio P A; Coutinho, Flavia L; Mannelli, Massimo; Recasens, Monica; Demarquet, Lea; Petramala, Luigi; Yaremchuk, Svetlana; Zabolotnyi, Dmitry; Schiavi, Francesca; Opocher, Giuseppe; Racz, Karoly; Januszewicz, Andrzej; Weryha, Georges; Henry, Jean-Francois; Brue, Thierry; Conte-Devolx, Bernard; Eng, Charis; Neumann, Hartmut P H

2014-05-01

The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339

Chlamydia trachomatis infection and human papillomavirus in women with cervical neoplasia in Pernambuco-Brazil.

PubMed

Tavares, Mayara Costa Mansur; de Macêdo, Jamilly Lopes; de Lima Júnior, Sérgio Ferreira; de Andrade Heráclio, Sandra; Amorim, Melânia Maria Ramos; de Mascena Diniz Maia, Maria; de Souza, Paulo Roberto Eleutério

2014-02-01

Chlamydia trachomatis (CT) is the most common bacterial cause of sexually transmitted disease. High-risk human papillomavirus (HR-HPV) is considered the main etiological agent for cervical neoplasia. Evidences showed that the presence of co-infection of CT and HR-HPV plays a central role in the etiology of cervical intraepithelial neoplasia (CIN) and cervical cancer. The goals of this study were: evaluate the human papillomavirus (HPV) and CT prevalence among Brazilian women with abnormal cytology and provide the effect of this association on the severity of cervical neoplasia. The population of this study was composed by 142 women with incident histological incidence of CIN grades I, II, III or cervical cancer from Recife, Northeast of Brazil. The polymerase chain reaction method on a cervical brush specimen was used to detect both agents and the automatic sequencing method was used for HPV genotyping assay. The prevalence of HPV and CT was 100 and 24.65 %, respectively. Thirteen types of HPV were detected; HPV 16, 18, 31 and 33 were the most common. The most prevalent HPV types were HPV 16 and 18. A significant association between CT positive and HPV 16 infection was found (p < 0.0106; OR = 5.31; 95 % IC 1.59-17.67). In the study population, there was diversity of HPV infections, with high-risk types being the most common. Also, the data collected suggest that CT infection may play an important role in the natural history of HPV infection.

Penile intraepithelial neoplasia and other premalignant lesions of the penis.

PubMed

Crispen, Paul L; Mydlo, Jack H

2010-08-01

Invasive penile cancer is an aggressive malignancy that often requires partial or complete penile amputation. Premalignant penile lesions, such as penile intraepithelial neoplasia, will have been present prior to the development of invasive disease in a substantial percentage of patients. Early detection and treatment of premalignant penile lesions may prevent malignant progression while avoiding penile amputation. This review focuses on premalignant penile lesions and the associations of these lesions with the development of invasive penile cancer. Copyright 2010 Elsevier Inc. All rights reserved.

Photodynamic therapy of cervical intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

[Crossed renal ectopia in a patient with a complicated sigma neoplasia].

PubMed

Pérez-Sánchez, Luis Eduardo; Burneo-Esteves, Mauricio; Rosat-Rodrigo, Adriá; Baz-Figueroa, Caleb; Pérez-Álvarez, Antonio Dámaso; Barrera-Gómez, Manuel Ángel

2017-12-01

Crossed renal ectopia is a rare pathology that is often asymptomatic. Intraoperative detection with a sigma complicated neoplasia is more infrequent and requires correct management to avoid a renal ureteral injury. To present a case report of a patient with a sigma complicated neoplasia and a crossed renal ectopia detected incidentally. We present the case of a 62-year-old man that was submitted for emergency surgery for a sigma perforated neoplasm, and who presented with a previously undiagnosed left-side CRE. During surgery there was a need to insert 2-double-J stents as a guide to both ureters and to avoid any injury to them. Crossed renal ectopia is a rare, often asymptomatic entity, the diagnosis of which is usually incidental. In our case, the detection of a concomitant complicated neoplasm, required identification of both ureters due the anatomic doubt of its localization and to avoid them being injured. In conclusion, upon finding a casual crossed renal ectopia during an emergency surgery of sigma, we recommend the identification of the ureters to facilitate its location and to avoid any injury to the ureters. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Elevated Serum Gastrin Is Associated With a History of Advanced Neoplasia in Barrett’s Esophagus

PubMed Central

Wang, Judy S.; Varro, Andrea; Lightdale, Charles J.; Lertkowit, Nantaporn; Slack, Kristen N.; Fingerhood, Michael L.; Tsai, Wei Yann; Wang, Timothy C.; Abrams, Julian A.

2011-01-01

OBJECTIVES Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett’ s esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. METHODS We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. RESULTS A total of 95 patients were enrolled. The mean age was 64.7 (±10.0) years, and 70.5 % were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P = 0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95 % confidence interval (CI): 1.20–24.8). CONCLUSIONS In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression. PMID:19904251

[Usefulness of human papillomavirus testing in anal intraepithelial neoplasia screening in a risk behaviour population].

PubMed

Padilla-España, Laura; Repiso-Jiménez, Bosco; Fernández-Sánchez, Fernando; Frieyro-Elicegui, Marta; Fernández-Morano, Teresa; Pereda, Teresa; Rivas-Ruiz, Francisco; Redondo, Maximino; de-Troya Martín, Magdalena

2014-11-01

The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P<.005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Advanced colorectal neoplasia risk stratification by penalized logistic regression.

PubMed

Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F

2016-08-01

Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the [Formula: see text]-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance. © The Author(s) 2013.

p16 immunostaining in keratinocytic neoplasia in organ transplant recipients: Bowen's disease shows a characteristic pattern.

PubMed

Genders, Roel E; Beck, Samuel; Bouwes Bavinck, Jan Nico; van den Munckhof, Henk A M; Kouwenhoven, Stijn T P; de Koning, Maurits N C; de Gruijl, Frank R; Jenkins, David; Willemze, Rein; Quint, Koen D

2017-01-01

For selecting therapy, it is important to distinguish different types of keratinocytic neoplasia. It is sometimes difficult to make histopathologic diagnosis, especially in organ transplant recipients (OTR) who develop numerous lesions. To investigate p16 immunostaining in different types of keratinocytic neoplasia in OTR, we studied 59 actinic keratoses (AK), 51 Bowen' s disease (BD), 63 squamous cell carcinomas (SCC), 16 benign keratotic lesions (BKL) from 31 OTR patients and 25 controls (eczema and psoriasis). Tissue sections were stained for H&E and p16. We scored intensity, proportion and distribution of p16 positive lesional cells. In 19% of AK, 92% of BD, 35% of SCC and 12% of BKL more than 15% of lesional cells were p16-positive. In 16% of AK, 80% of BD, 18% of SCC and 13% of BKL strong p16 staining was observed. BKL, AK and SCC showed focal and patchy staining, BD showed diffuse pattern with strong staining of all atypical cells. Sparing of the basal layer was predominantly seen in BD. No control specimen showed p16-overexpression. p16 immunostaining shows a characteristic pattern in BD, but not in AK, SCC and BKL. It appears useful in recognizing BD, but not in differentiating between other keratinocytic neoplasia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Persistent regurgitation in four dogs with caudal esophageal neoplasia.

PubMed

Arnell, Katharine; Hill, Steve; Hart, John; Richter, Keith

2013-01-01

Esophageal neoplasia is an uncommon, but important, consideration for acute and chronic regurgitation and megaesophagus in dogs. The diagnosis can be challenging, and treatment options are often limited. This case series describes four dogs with regurgitation secondary to caudal esophageal masses. All dogs presented with regurgitation, and three of the four dogs had radiographically apparent megaesophagus. In all dogs, ancillary diagnostics revealed the presence of a caudal esophageal mass resulting in esophageal obstruction, and all mass lesions were histopathologically confirmed to be neoplastic. Treatment responses were variable, with one dog still alive 37 mo postdiagnosis at the time of manuscript preparation.

Candida and squamous (pre)neoplasia of immigrants and Dutch women as established in population-based cervical screening.

PubMed

Engberts, M K; Vermeulen, C F W; Verbruggen, B S M; van Haaften, M; Boon, M E; Heintz, A P M

2006-01-01

The objective of this study was to establish the relationship between Candida vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia related to age and ethnicity. Data were collected from 445,671 asymptomatic women invited for mass screening between 1995 and 2002 and coded according to the Dutch cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes. Prevalence and relative risks (RRs) were established for Candida and squamous abnormalities in Dutch women and four groups of immigrants. The prevalence of Candida is significantly higher in the cohort of 30-year-old women and lower in the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI 1.13-1.62). No statistically significant relationship between (pre)neoplasia and Candida was observed. C. vaginalis is more frequent among Surinamese women. Presence of Candida is not associated with an increased risk for squamous abnormalities; therefore, women carrying Candida are not at an increased risk of developing cervical cancer.

Vulvar intraepithelial neoplasia--the need for auditable measures of management.

PubMed

Athavale, Ram; Naik, R; Godfrey, K A; Cross, P; Hatem, M H; de Barros Lopes, A

2008-03-01

Surgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We propose auditable indicators of performance to benchmark management and outcomes. This may also enable definition of a surgical control arm for future novel therapy studies. Data from the Northern Gynaecological Oncology Centre (NGOC), UK on women with proven VIN diagnosed between 1989 and 2004 who attended the vulvar review clinic are presented and analysed alongside three large retrospective series by Jones et al. [Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol 2005;106(6):1319-26], Herod et al. [Herod JJ, Shafi MI, Rollason TP, Jordan JA, Luesley DM. Vulvar intraepithelial neoplasia: long term follow up of treated and untreated women. Br J Obstet Gynaecol 1996;103(5):446-52], McNally et al. [McNally OM, Mulvany NJ, Pagano R, Quinn MA, Rome RM. VIN 3: a clinicopathologic review. Int J Gynecol Cancer 2002;12(5):490-5] against proposed performance indicators to illustrate the deficiencies in current data presentation. Demographics and indicators such as degree of pathological expertise, definition of early stromal invasion and use of International Society for the study of Vulvovaginal Disease (ISSVD) classification were usually well documented. The description of lesions including size and focality were not always documented, nor the proportion examined by co-specialists. Numbers of primary treatments were well described but the indications for treatment, completeness of excision and VIN subclassification were not. Subsequent surgical treatments were inconsistently reported

Papiloma invertido sinunasal con invasión intracraneal: Reporte de caso y revisión bibliográfica

PubMed Central

Di Pietrantonio, Andrés; Asmus, Humberto; Ingratta, Christian; Brennan, Walter; Schulz, Javier; Carballo, Leandro

2018-01-01

Resumen IntroducciÓn: El papiloma invertido es una neoplasia benigna de los senos paranasales localmente agresiva con alto potencial de recurrencia y de malignización. La extensión intracraneal es infrecuente y más aún, la penetración dural, asociándose a menudo a la recurrencia de la enfermedad o a su degeneración en carcinoma de células escamosas. Caso clínico: Presentamos el caso de una paciente de 32 años que consultó por lesión exofítica en fosa nasal derecha y exoftalmos, asociada a cefalea, anosmia y disgeusia. Se estudió con TC cerebro, macizo facial y RM de encéfalo que evidencian lesión en fosa nasal derecha con ocupación de senos aéreos, osteólisis de pared medial orbitaria y base de cráneo anterior e invasión intracraneal frontal derecha, con efecto de masa y compresión del parénquima encefálico adyacente. Intervención: Se realizó una nasofibroscopía en primer tiempo con diagnóstico anatomopatológico de papiloma invertido y posteriormente resección de la lesión mediante doble abordaje más reconstrucción de la fosa craneal anterior. Se obtuvo diagnóstico definitivo de papiloma invertido de tipo Schneideriano con áreas de transformación atípica in situ. La paciente evolucionó de forma favorable y sin complicaciones, con permeabilidad de vía aérea superior, sin signos de recidiva lesional luego de 4 años de seguimiento. Conclusión: La invasión intracraneal de esta patología es sumamente infrecuente. Cuando existe, es indicador de agresividad y potencial recidiva, por lo que la exéresis completa de la misma define el pronóstico de la enfermedad. PMID:29430328

Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia: Establishing the Baseline for Surveillance

PubMed Central

Nygård, Mari; Hansen, Bo Terning; Dillner, Joakim; Munk, Christian; Oddsson, Kristján; Tryggvadottir, Laufey; Hortlund, Maria; Liaw, Kai-Li; Dasbach, Erik J.; Kjær, Susanne Krüger

2014-01-01

Background Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004–2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. Methods Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. Results Among the four countries, the age-standardised IR/105 of cervical, vaginal and vulvar cancer ranged from 8.4–13.8, 1.3–3.1 and 0.2–0.6, respectively. The risk for cervical cancer was highest in women aged 30–39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/105 of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8−183.2, 2.5−8.8 and 0.5−1.3, respectively. Women aged 20−29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40−49 and 60−69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004−2006 can be attributed to HPV16/18. Conclusion In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of

Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis).

PubMed

Rodriguez Barbon, A; Cowen, R; Knott, C; Hughes, K; Allinson, K; Williams, C V; Routh, A

2018-02-01

Tumours diagnosed in three aged captive aye-ayes (Daubentonia madagascariensis), held in two different institutions, are described. A cerebral glioblastoma was diagnosed based on histological and immunohistochemical findings in one of the animals following initial presentation with bilateral mydriasis, absent pupillary reflex, head tilt and ataxia. A second animal was humanely destroyed due to impaired locomotion associated with spondylosis and a post-mortem diagnosis of cholangiocarcinoma was made based on histology with further confirmation with immunohistochemical labelling for cytokeratin 7. A third aye-aye suffering from dental disease was diagnosed with an oral squamous cell carcinoma following an excisional biopsy from a non-healing wound in the lip. Due to progression of the neoplasia the animal was humanely destroyed and post-mortem examination revealed the presence on an additional unilateral phaeochromocytoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biomarkers of Risk for Colorectal Neoplasia (Team Project #2) — EDRN Public Portal

Cancer.gov

The goal of this project is to evaluate biomarkers in normal colonic mucosa to determine their relationship to the occurrence of short- and long-term colorectal neoplasia. Candidate markers have been proposed by participating investigators based on promising preliminary data. The purpose of this team project is to evaluate these markers in a common, tissue-based reference set, under a uniform, structured protocol.

Development of surrogate endpoint biomarkers for clinical trials of cancer chemopreventive agents: relationships to fundamental properties of preinvasive (intraepithelial) neoplasia.

PubMed

Boone, C W; Kelloff, G J

1994-01-01

The tissue changes offering the greatest immediate potential for development as surrogate endpoint biomarkers (SEBs) to be used in Phase II trials of cancer chemopreventive agents are those derived from the microscopic tissue changes pathologists use to make the diagnosis of preinvasive (intraepithelial) neoplasia. These changes comprise four categories: proliferative index, ploidy, nuclear morphometry (size, shape, texture, and pleomorphism), and nucleolar morphometry (number, size, shape, position, and pleomorphism). Computer-assisted image analysis (CIA) permits dozens of additional morphometric parameters to be developed. Other categories of candidate SEBs are: DNA and chromosomal structural changes associated with genomic instability, activation of oncogenes and inactivation of tumor suppressor genes, structural changes in differentiated molecules, and aberrations of growth factor/receptor structure and function. Self-perpetuating DNA breakage with secondary mutator mutations in genomic stability genes is a major mechanism by which the genomic instability characteristic of neoplasia occurs, and from which stem other basic neoplastic properties, including clonal evolution, along multiple pathways of genetic variation that are stochastically determined, continuously increasing proliferation, rate and extent of phenotypic heterogeneity. SEBs resulting from genomic instability include homogeneously staining regions, double minute chromosomes, micronuclei, dicentrics, gene amplification, loss of heterozygosity, and alterations in chromosome number. Newly developed assays for detecting genomic instability include comparative genomic hybridization using fluorescence in situ hybridization on > 20 micron-thick sections monitored by confocal laser scanning microscopy, assays for microsatellite instability, and restriction landmark genomic scanning. These assays offer promise for detecting the earliest molecular changes of neoplasia in normal-appearing epithelium prior

Confocal laser endomicroscopy for in vivo diagnosis of Barrett's oesophagus and associated neoplasia: a pilot study conducted in a single Italian centre.

PubMed

Trovato, Cristina; Sonzogni, Angelica; Ravizza, Davide; Fiori, Giancarla; Tamayo, Darina; De Roberto, Giuseppe; de Leone, Annalisa; De Lisi, Stefania; Crosta, Cristiano

2013-05-01

Diagnosis and management of Barrett's oesophagus are controversial. Technical improvements in real-time recognition of intestinal metaplasia and neoplastic foci provide the chance for more effective target biopsies. Confocal laser endomicroscopy allows to analyze living cells during endoscopy. To assess the diagnostic accuracy, inter- and intra-observer variability of endomicroscopy for detecting in vivo neoplasia (dysplasia and/or early neoplasia) in Barrett's oesophagus. Prospective pilot study. Patients referred for known Barrett's oesophagus were screened. Endomicroscopy was carried out in a circular fashion, every 1-2 cm, on the whole columnar-lined distal oesophagus. Visible lesions, when present, were analyzed first. Targeted biopsies were taken. Confocal images were classified according to confocal Barrett classification. Endomicroscopic and histological findings were compared. Forty-eight out of 50 screened patients underwent endomicroscopy. Visible lesions were observed in 3 patients. In a per-biopsy analysis, Barrett's-oesophagus-associated neoplasia could be predicted with an accuracy of 98.1%. The agreement between endomicroscopic and histological results was substantial (κ=0.76). This study suggests that endomicroscopy can provide in vivo diagnosis of Barrett's oesophagus-associated neoplasia. Because it allows for the study of larger surface areas of the mucosa, endomicroscopy may lead to significant improvements in the in vivo screening and surveillance of Barrett's oesophagus. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Abraham Lincoln's marfanoid mother: the earliest known case of multiple endocrine neoplasia type 2B?

PubMed

Sotos, John G

2012-07-01

The nature and cause of President Abraham Lincoln's unusual physical features have long been debated, with the greatest attention directed at two monogenic disorders of the transforming growth factor β system: Marfan syndrome and multiple endocrine neoplasia type 2B. The present report examines newly discovered phenotypic information about Lincoln's biological mother, Nancy Hanks Lincoln, and concludes that (a) Lincoln's mother was skeletally marfanoid, (b) the President and his mother were highly concordant for the presence of numerous facial features found in various transforming growth factor β disorders, and (c) Lincoln's mother, like her son, had hypotonic skeletal muscles, resulting in myopathic facies and 'pseudodepression'. These conclusions establish that mother and son had the same monogenic autosomal dominant marfanoid disorder. A description of Nancy Hanks Lincoln as coarse-featured, and a little-known statement that a wasting disease contributed to her death at age 34, lends support to the multiple endocrine neoplasia type 2B hypothesis.

Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

NASA Astrophysics Data System (ADS)

Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

2008-02-01

Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

[Crosssectional survey of human papilloma virus subtype distribution and cervical intraepithelial neoplasia in Shenzhen].

PubMed

Liang, Ling-yun; Du, Hui; Wang, Chun; Zhang, Wei; Chen, Yun; Qu, Xin-feng; Yang, Bin; Wu, Bo; Wu, Ruo-song; Belinson, Jerome L; Wu, Rui-fang

2013-02-18

To investigate the prevalence of human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) and pathogenecity of the HPV subtyping and virus loads in Shenzhen district. In the study, 10 000 sexually active women from Shenzhen city and rural areas around were screened for cervical cancer, and all the cases were examined with cytology tests and several kinds of high risk HPV (HR-HPV) tests. Those with cytology ≥atypical squamous cells of undetermined sign (ASC-US) or positive HPV results underwent colposcopy with biopsy for a pathological diagnosis. The average age of this study population was 38.9 years. The total prevalence of HPV infection was 16.6%, with age-specific prevalence increasing with age. The morbidity rate of the low grade cervical intraepithelial neoplasia CIN1 was 17.0%, but that with those aged ≥55 years showed a sharp drop. The morbidity rate of the high grade cervical intraepithelial neoplasia CIN2/3 was 2.6%, and was higher in the 45 to 59 years age group than in the 25 to 44 years age group. HR-HPV infection was an obvious relevant factor of CIN1 and CIN2/3, and the OR values increased as the virus loads increased, but they had different relevant HPV subtypes. We found that HPV-16, -58, -31, -33, -18 were the first five ones for CIN2/3 while HPV-39, -58, -59, -52, -66 for CIN1. There is a high level of HPV infection and CIN in Shenzhen district. The prevalence of HPV infection has a trend to increase with age, and the people aged 45 years and more are key objects for CIN2/3 screening, with the virus load and subtyping of HR-HPV infection as indicative factors.

Specific immune cell and cytokine characteristics of human testicular germ cell neoplasia.

PubMed

Klein, Britta; Haggeney, Thomas; Fietz, Daniela; Indumathy, Sivanjah; Loveland, Kate L; Hedger, Mark; Kliesch, Sabine; Weidner, Wolfgang; Bergmann, Martin; Schuppe, Hans-Christian

2016-10-01

Which immune cells and cytokine profiles are characteristic for testicular germ cell neoplasia and what consequences does this have for the understanding of the related testicular immunopathology? The unique immune environment of testicular germ cell neoplasia comprises B cells and dendritic cells as well as high transcript levels of IL-6 and other B cell supporting or T helper cell type 1 (Th1)-driven cytokines and thus differs profoundly from normal testis or inflammatory lesions associated with hypospermatogenesis. T cells are known to be the major component of inflammatory infiltrates associated with either hypospermatogenesis or testicular cancer. It has previously been reported that B cells are only involved within infiltrates of seminoma samples, but this has not been investigated further. Immunohistochemical characterisation (IHC) of infiltrating immune cells and RT-qPCR-based analysis of corresponding cytokine microenvironments was performed on different testicular pathologies. Testicular biopsies, obtained from men undergoing andrological work-up of infertility or taken during surgery for testicular cancer, were used in this study. Samples were grouped as follows: (i) normal spermatogenesis (n = 18), (ii) hypospermatogenesis associated with lymphocytic infiltrates (n = 10), (iii) samples showing neoplasia [germ cell neoplasia in situ (GCNIS, n = 26) and seminoma, n = 18]. IHC was performed using antibodies against T cells (CD3+), B cells (CD20cy+), dendritic cells (CD11c+), macrophages (CD68+) and mast cells (mast cell tryptase+). Degree and compartmental localisation of immune cells throughout all groups analysed was evaluated semi-quantitatively. RT-qPCR on RNA extracted from cryo-preserved tissue samples was performed to analyse mRNA cytokine expression, specifically levels of IL-1β, IL-6, IL-17a, tumour necrosis factor (TNF)-α (pro-inflammatory), IL-10, transforming growth factor (TGF)-β1 (anti-inflammatory), IL-2, IL-12a, IL-12b

Long-term follow-up results of stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia.

PubMed

Belghazi, Kamar; van Vilsteren, Frederike G I; Weusten, Bas L A M; Meijer, Sybren L; Bergman, Jacques J G H M; Pouw, Roos E

2018-01-01

Stepwise radical endoscopic resection (SRER) has shown to be effective in eradicating Barrett's esophagus (BE) and its associated dysplasia. The aim of this study was to assess the long-term durability after successful SRER for early Barrett's neoplasia. Patients treated with SRER for BE ≤5 cm with high-grade dysplasia (HGD) or early cancer (EC) and who had reached complete eradication of intestinal metaplasia (CE-IM) and neoplasia (CE-neo) were included. Primary outcomes were recurrence of neoplasia (HGD/EC), recurrence of dysplasia (indefinite for dysplasia included), and recurrence of endoscopically visible BE. Secondary outcomes were buried Barrett's glands, IM in biopsy specimens obtained distal to a normal-appearing neo-squamocolumnar junction (neo-SCJ), need for retreatment, and sustained CE-IM and CE-neo at the last follow-up endoscopy. Seventy-three patients were included (64 men; mean age, 66 years; median BE, C2M3). Median follow-up was 76 months. Recurrence of neoplasia was observed in 1 patient (T1bN0M0) after 129 months of follow-up and was treated with curative surgery (annual incidence of .22% per patient-year of follow-up). In 4 patients, recurrence of dysplasia was found (.87% per patient-year of follow-up). Twelve patients had recurrent endoscopically visible BE after a median follow-up of 22 months (2.6% per patient-year of follow-up), mostly small islands or tongues. Five patients had a single finding of buried Barrett's glands (1.1% per patient-year of follow-up), and 27 patients (5.9% per patient-year of follow-up) showed IM in biopsy specimens just distal to the neo-SCJ, which was not reproduced in 56%. Retreatment was performed in 9 patients. CE-IM and CE-neo (excluding IM in the neo-SCJ) at the last follow-up endoscopy was seen in 95% and 97% of patients, respectively. This study presents the longest published follow-up data on SRER to date. The 6-year outcomes show that successful SRER is a durable treatment for BE ≤5 cm with HGD

Anal cytology as a predictor of anal intraepithelial neoplasia in HIV-positive men and women.

PubMed

Betancourt, Eve M; Wahbah, Mary M; Been, Laura C; Chiao, Elizabeth Y; Citron, Deborah R; Laucirica, Rodolfo

2013-08-01

Human immunodeficiency virus (HIV)-infected individuals have increased risk of anal intraepithelial neoplasia (AIN) and squamous cell carcinoma (SCC). Cytologic screening is invaluable in the detection of cervical neoplasia, therefore many clinicians have adopted anal cytology as part of anal cancer screening in patients at high-risk for anal neoplasia. The purpose of this study is to determine whether anal cytology is a valuable screening test for identifying AIN in HIV+ patients. The cohort included 228 HIV+ patients who underwent anal cancer screening with collection of 318 anal cytology specimens between January 2006 and December 2009. Of this group, 74 (32.5%) patients had associated anal biopsies within a 6-month period, with a total of 89 comparison cases. The anal cytology samples were classified using the 2001 Bethesda System terminology. The sensitivity of anal cytology in detecting ASC-US, AIN 1-3 or SCC was 93%. Cytology was 88% sensitive for detecting low-grade AIN (AIN 1), but only 20% sensitive for detecting high-grade AIN (AIN 2-3) or SCC. Atypical squamous cells of undetermined significance cases were distributed evenly between low- and high-grade AIN, with two cases having normal histology. Only six cases had negative cytology, all of which were associated with AIN on biopsy, for a false negative rate of 7%. Anal cytology is a good predictor of AIN, as confirmed by the high degree of sensitivity. However, there is poor correlation between the cytological and histological grade of AIN. Cytology underestimates the grade of dysplasia compared to the corresponding biopsy. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.

PubMed

Singhi, Aatur D; Zeh, Herbert J; Brand, Randall E; Nikiforova, Marina N; Chennat, Jennifer S; Fasanella, Kenneth E; Khalid, Asif; Papachristou, Georgios I; Slivka, Adam; Hogg, Melissa; Lee, Kenneth K; Tsung, Allan; Zureikat, Amer H; McGrath, Kevin

2016-06-01

The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI

CO2 laser surgery for vulvar intraepithelial neoplasia. Excisional, destructive and combined techniques.

PubMed

Penna, Carlo; Fallani, M Grazia; Fambrini, Massimiliano; Zipoli, Elisa; Marchionni, Mauro

2002-11-01

To evaluate CO2 laser excision, vaporization and combined techniques for treatment of vulvar intraepithelial neoplasia (VIN). Thirty-nine cases of VIN 3, 15 cases of VIN 2 and 9 of VIN 1, for a total of 63 patients with histologically proven VIN, underwent laser excision or vaporization under colposcopic guidance, using local anesthesia, in an outpatient setting or after day-surgery admission. Clinical aspects, cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VaIN) association, types of CO2 laser treatment, follow-up, recurrences and second treatments were evaluated. Twenty-seven (41.3%) patients underwent laser vaporization, and 37 (58.7%) with VIN 3, underwent laser excision or the combined technique. Colposcopic and biopsy examinations of patients with VIN revealed three cases of CIN 3 and nine cases of VaIN 3; two patients had concomitant VIN 3, CIN 3 and VaIN 3. Local anesthesia, using 2% carbocaine, and outpatient or day-surgery treatments were possible in all cases. A small incidence of intraoperative complications (4.8%) and absence of postoperative complications were observed. A single session was curative in 76.9% of patients treated with laser vaporization and in 78.4% of those treated with laser excision. Eleven cases of recurrent VIN and two cases of invasive vulvar carcinoma were observed during follow-up. A second laser procedure was carred out in all cases of relapsed VIN, with an overall cure rate of 96.8% after two treatments. Radical vulvectomy associated with inguinal-femoral lymphadenectomy was performed in the two cases of invasive carcinoma. CO2 laser surgery permits treatment of VIN in an outpatient or day-surgery setting under local anesthesia with excellent cosmetic and functional results. The treatment can also be adjusted to the patient's specific needs, with the possibility of calibrating the depth of the vaporized and removed tissues. Excisional treatment is the preferred method because it permits

Neoplasia in 125 donkeys (Equus asinus): literature review and a survey of five veterinary schools in the United States and Canada.

PubMed

Davis, Corrine R; Valentine, Beth A; Gordon, Emma; McDonough, Sean P; Schaffer, Paula A; Allen, Andrew L; Pesavento, Patricia

2016-11-01

A diagnosis of neoplasia was noted in 125 of 357 donkeys (35%) in our review of medical records from 5 veterinary schools in the United States and Canada. Equine sarcoid was the most common tumor in our study, accounting for 72% of all tumors and 82% of cutaneous tumors. Soft-tissue sarcomas were the second most common skin tumors. All other types of neoplasia were rare. Important differences in the occurrence of neoplasia in donkeys compared to horses included the rarity or absence of squamous cell carcinoma in any organ system and gray horse melanoma. Lymphosarcoma, the most common malignant tumor in horses, appears to be very rare in donkeys. We report several tumors in donkeys including melanocytoma, peripheral nerve sheath tumor, and gastrointestinal stromal tumor. Our data demonstrate commonalities as well as differences in neoplastic diseases of donkeys and horses. Understanding differences in carcinogenesis among these 2 closely related species can inform researchers pursuing pathogenic mechanisms of equine disease and inform veterinary diagnosticians regarding tumor prevalence. © 2016 The Author(s).

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

PubMed Central

Chatrath, P; Scott, I S; Morris, L S; Davies, R J; Bird, K; Vowler, S L; Coleman, N

2006-01-01

We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n=8), laryngeal dysplasia (n=10) and laryngeal squamous cell carcinoma (n=10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (ρ=0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P=0.001), Ki67 (P=0.0002), cyclin D1 (P=0.015), cyclin A (P=0.0001) and cyclin B1 (P=0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia. PMID:16832409

Secondary prevention of cervical cancer part 3: evidence-based management of women with cervical intraepithelial neoplasia.

PubMed

Guido, Richard; Lonky, Neal M; Diedrich, Justin

2014-06-01

The management of cervical intraepithelial neoplasia has evolved over the last 20 years. Observation has replaced aggressive therapy in many cases. Evidence based guidelines now guide therapy. This chapter presents an overview of various treatment options, as well as the most recent guidelines of therapy.

Proceedings From the First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting

PubMed Central

Faro, Edited by Sebastian

2006-01-01

The First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia, in July 2005. The conference covered regional issues relating to infection with the human papillomavirus—epidemiology, virology, and immunology, testing, screening, and prevention strategies—as well as cervical cancer screening and its management.

Carbon dioxide laser management cervical intraepithelial neoplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bellina, J.H.; Wright, V.C.; Voros, J.I.

1981-12-01

In this report we describe the use of the carbon dioxide laser for the outpatient management of cervical intraepithelial neoplasia (CIN). A comparison of treatment effectiveness for different grades of CIN is also included. Two hundred fifty-six cases were evaluated by colposcopy, cytology, and histopathology, treated by at least 5 to 6 mm of laser vaporization, and followed up for an average of 10.7 months. Follow-up examinations included cytology, colposcopy, and directed biopsy if a suspicious lesion was discovered. During the follow-up, 18 cases of persistent CIN were identified (7.0%). Most of these were successfully managed with repeat laser treatment.more » Overall success of laser surgery for CIN, one or two applications, was 97.6%. Few complications were encountered. Laser surgery appears to offer acceptable treatment effectiveness, early identification of persistent disease, and easy retreatment when required. (Am. J. Obstet. Gynecol. 141:828, 1981.)« less

Perceived Health-Related Quality of Life in Women With Vulvar Neoplasia: A Cross Sectional Study.

PubMed

Kobleder, Andrea; Nikolic, Nataša; Hechinger, Mareike; Denhaerynck, Kris; Hampl, Monika; Mueller, Michael D; Senn, Beate

2016-09-01

The aim of the study was to determine health-related quality of life (HRQoL) of women with surgically treated vulvar intraepithelial neoplasia (VIN) and vulvar cancer (VC) during the first week after hospital discharge. Further objectives were to investigate differences between women with VIN and VC as well as to examine whether correlations exist between women's symptom experience and HRQoL. This cross-sectional study was conducted in 8 hospitals in Germany and Switzerland. Women with VIN and VC rated HRQoL with the validated German Short-Form 36. Differences between HRQoL in women with VIN and VC were tested with Wilcoxon rank-sum score. The WOMen with vulvAr Neoplasia (WOMAN) - Patient reported Outcome (PRO) self-report instrument was used to measure women's symptom experience. Correlations between symptoms and HRQoL were calculated using Spearman correlation coefficient. Women with VIN and VC (n = 65) reported lower HRQoL in physical aspects (Physical Component Summary [PCS], 34.9) than that in mental aspects (Mental Component Summary, 40.5). Women with VC had lower HRQoL than women with VIN, as manifested by significant differences concerning the dimensions of "physical functioning" and "role-physical." "Difficulties in daily life" as a distressing symptom correlated with MCS and PCS. Wound-related symptoms correlated with PCS and psychosocial symptoms/issues with MCS. Analysis showed that women with vulvar neoplasia reported lower HRQoL in the physical and mental dimensions 1 week after discharge than comparable studies referring to months or years after surgery. Health-related quality of life is influenced by physical impairment because physical symptoms are prevalent 1 week after discharge. Patient education should focus on symptom management in an early postsurgical phase to enhance women's HRQoL.

Long-term outcomes after adjunctive topical 5-flurouracil or mitomycin C for the treatment of surgically excised, localized ocular surface squamous neoplasia.

PubMed

Bahrami, Bobak; Greenwell, Timothy; Muecke, James S

2014-01-01

To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision. Long-term follow up of two prospective, non-comparative interventional case series. One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C. Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles. Ocular surface squamous neoplasia recurrence, complications of therapy and compliance. Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted. Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.

PubMed

Srigley, John R; Delahunt, Brett; Eble, John N; Egevad, Lars; Epstein, Jonathan I; Grignon, David; Hes, Ondrej; Moch, Holger; Montironi, Rodolfo; Tickoo, Satish K; Zhou, Ming; Argani, Pedram

2013-10-01

The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC

Sexually transmitted agents and cervical neoplasia in Colombia and Spain.

PubMed

de Sanjosé, S; Muñoz, N; Bosch, F X; Reimann, K; Pedersen, N S; Orfila, J; Ascunce, N; González, L C; Tafur, L; Gili, M

1994-02-01

Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.

Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

PubMed

Ionescu, E M; Nicolaie, T; Ionescu, M A; Becheanu, G; Andrei, F; Diculescu, M; Ciocirlan, M

2015-01-01

DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating

GLUT-1 expression in pancreatic neoplasia: implications in pathogenesis, diagnosis, and prognosis.

PubMed

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N Volkan

2011-03-01

GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression.

Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

PubMed

Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

2008-05-01

To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system.

PubMed

Curvers, W L; Singh, R; Song, L-M Wong-Kee; Wolfsen, H C; Ragunath, K; Wang, K; Wallace, M B; Fockens, P; Bergman, J J G H M

2008-02-01

To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett's oesophagus. Prospective multi-centre study. Tertiary referral centres. 84 Patients with Barrett's oesophagus. The Barrett's oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett's oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.

LASER treatment for women with high-grade vaginal intraepithelial neoplasia: A propensity-matched analysis on the efficacy of ablative versus excisional procedures.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Mosca, Lavinia; Chiappa, Valentina; Rossetti, Diego; Leone Roberti Maggiore, Umberto; Sabatucci, Ilaria; Lorusso, Domenica; Raspagliesi, Francesco

2018-05-14

To investigate the long-term effectiveness of LASER treatment in women affected by high-grade vaginal intra-epithelial neoplasia. Data of consecutive women treated for high-grade vaginal intra-epithelial neoplasia were retrieved. Efficacy and long-term effectiveness of ablative and excisional procedures were tested using a propensity-matched algorithm. Risk of recurrence over the time was assessed using Kaplan-Meier and Cox models. Overall, 204 patients met the inclusion criteria. LASER ablation and exicision were performed in 169 (82.8%) and 35 (17.2%) patients. A total of 41 (20%) patients developed high-grade vaginal intraepithelial neoplasia at a median follow-up of 65 (range, 6-120) months. We observed that only HPV persistence (HR: 2.37 [95%CI:1.03, 5.42]; P = 0.04) was associated with the risk of recurrence at multivariate analysis. Seven (3.4%) invasive cancers of the lower genital tract were observed in our population. Considering the efficacy of type of procedure (after we applied the propensity-matched analysis), we observed that type of procedure did not influence persistence of HPV infection (22.8% after excision and 15.7% after ablation; P = 0.424). Similarly, recurrence (17.1% vs. 18.6%; P = 1.00) and lower genital tract (2.8% vs. 1.4%; P = 1.00) rates were similar between groups. Women affected by high-grade vaginal intra-epithelial neoplasia are at high risk of recurrence. LASER ablation seems to be equivalent to excision in term of long-term effectiveness. Lasers Surg. Med. 9999:1-7, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Faecal haemoglobin concentration is related to detection of advanced colorectal neoplasia in the next screening round.

PubMed

Digby, Jayne; Fraser, Callum G; Carey, Francis A; Diament, Robert H; Balsitis, Margaret; Steele, Robert Jc

2017-06-01

Objective To examine associations between faecal haemoglobin concentrations below the cut-off used in colorectal cancer screening and outcomes in the next screening round. Methods In the Scottish Bowel Screening Programme, faecal haemoglobin concentrations and diagnostic outcomes were investigated for participants with a negative result (faecal haemoglobin concentrations < 80.0 µg Hb/g faeces), followed by a positive result within two years. Results Of 37,780 participants with negative results, at the next screening round, 556 (1.5%) screened positive and 30,293 (80.2%) negative. Initial median faecal haemoglobin concentrations (2.1 µg Hb/g faeces, IQR: 0.0-13.2) were higher in those with subsequent positive results than those with subsequent negative results (0.0 µg Hb/g faeces, IQR: 0.0-1.4; p < 0.0001). Using faecal haemoglobin concentrations 0.0-19.9 µg Hb/g faeces as reference, logistic regression analysis showed high adjusted odds ratios for advanced neoplasia (advanced neoplasia: colorectal cancer or higher risk adenoma) detection at the next round of 14.3 (95% CI: 8.9-23.1) in those with initial faecal haemoglobin concentrations 20.0-39.9 µg Hb/g faeces, and 38.0 (95% CI: 20.2-71.2) with 60.0-79.9 µg Hb/g faeces. Conclusions A higher proportion of participants with faecal haemoglobin concentrations of ≥ 20 µg Hb/g faeces had advanced neoplasia detected at the next round than participants with lower faecal haemoglobin concentrations. Although most relevant when using high faecal haemoglobin concentrations cut-offs, studies of faecal haemoglobin concentrations and outcomes over screening rounds may provide strategies to direct available colonoscopy towards those at highest risk.

Evaluation of DNA Single and Double Strand Breaks in Women with Cervical Neoplasia Based on Alkaline and Neutral Comet Assay Techniques

PubMed Central

Cortés-Gutiérrez, Elva I.; Hernández-Garza, Fernando; García-Pérez, Jorge O.; Dávila-Rodríguez, Martha I.; Aguado-Barrera, Miguel E.; Cerda-Flores, Ricardo M.

2012-01-01

A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r2 = 0.99, P = 0.03, and r2 = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb. PMID:23093842

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X.

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia.

PubMed

Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Management of early colonic neoplasia: where are we now and where are we heading?

PubMed

Longcroft-Wheaton, Gaius; Bhandari, Pradeep

2017-03-01

There have been considerable advances in the endoscopic treatment of colorectal neoplasia. The development of endoscopic submucosal dissection and full thickness resection techniques is changing the way benign disease and early cancers are managed. This article reviews the evidence behind these new techniques and discusses where this field is likely to move in the future. Areas covered: A PubMed literature review of resection techniques for colonic neoplasia was performed. The clinical and cost effectiveness of endoscopic mucosal resection (EMR) is examined. The development of endoscopic submucosal dissection (ESD) and knife assisted resection is described and issues around training reviewed. Efficacy is compared to both EMR and transanal endoscopic microsurgery. The future is considered, including full thickness resection techniques and robotic endoscopy. Expert commentary: The perceived barriers to ESD are falling, and views that such techniques are only possible in Japan are disappearing. The key barriers to uptake will be training, and the development of educational programmes should be seen as a priority. The debate between TEMS and ESD will continue, but ESD is more flexible and cheaper. This will become less significant as the number of endoscopists trained in ESD grows and some TEMS surgeons may shift across towards ESD.

The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants.

PubMed

Wong, Martin C S; Ching, Jessica Y L; Ng, Simpson; Lam, Thomas Y T; Luk, Arthur K C; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

2016-02-03

We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50-70 years in a colonoscopy screening programme(2008-2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56-0.65, with sensitivities ranging from 0.04-0.44 and specificities from 0.74-0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58-0.72). The NNS (12-19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed.

Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice.

PubMed

Cheon, Eric C; Strouch, Matthew J; Barron, Morgan R; Ding, Yongzeng; Melstrom, Laleh G; Krantz, Seth B; Mullapudi, Bhargava; Adrian, Kevin; Rao, Sambasiva; Adrian, Thomas E; Bentrem, David J; Grippo, Paul J

2011-06-15

Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-Kras(G12D) (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid. Copyright © 2010 UICC.

EMR is not inferior to ESD for early Barrett’s and EGJ neoplasia: An extensive review on outcome, recurrence and complication rates

PubMed Central

Komeda, Yoriaki; Bruno, Marco; Koch, Arjun

2014-01-01

Background and study aims In recent years, it has been reported that early Barrett’s and esophagogastric junction (EGJ) neoplasia can be effectively and safely treated using endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Multiband mucosectomy (MBM) appears to be the safest EMR method. The aim of this systematic review is to assess the safety and efficacy of MBM compared with ESD for the treatment of early neoplasia in Barrett’s or at the EGJ. Methods A literature review of studies published up to May 2013 on EMR and ESD for early Barrett’s esophagus (BE) neoplasia and adenocarcinoma at the EGJ was performed through MEDLINE, EMBASE and the Cochrane Library. Results on outcome parameters such as number of curative resections, complications and procedure times are compared and reported. Results A total of 16 studies met the inclusion criteria for analysis in this study. There were no significant differences in recurrence rates when comparing EMR (10/380, 2.6 %) to ESD (1/333, 0.7 %) (OR 8.55; 95 %CI, 0.91 – 80.0, P = 0.06). All recurrences after EMR were treated with additional endoscopic resection. The risks of delayed bleeding, perforation and stricture rates in both groups were similar. The procedure was considerably less time-consuming in the EMR group (mean time 36.7 min, 95 %CI, 34.5 – 38.9) than in the ESD group (mean time 83.3 min, 95 %CI, 57.4 – 109.2). Conclusions The MBM technique for EMR is as effective as ESD when comparing outcomes related to recurrence and complication rates for the treatment of early Barrett’s or EGJ neoplasia. The MBM technique is considerably less time-consuming. PMID:26135261

Fluorescence detection of esophageal neoplasia

NASA Astrophysics Data System (ADS)

Borisova, E.; Vladimirov, B.; Avramov, L.

2008-06-01

White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

Dysregulation of the Phosphatidylinositol 3-kinase Pathway in Thyroid Neoplasia

PubMed Central

Paes, John E.; Ringel, Matthew D.

2008-01-01

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is an important regulator of many cellular events, including apoptosis, proliferation, and motility. Enhanced activation of this pathway can occur through several mechanisms, such as inactivation of its negative regulator, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and activating mutations and gene amplification of the gene encoding the catalytic subunit of PI3K (PIK3CA). These genetic abnormalities have been particularly associated with follicular thyroid neoplasia and anaplastic thyroid cancer, suggesting an important role for PI3K signaling in these disorders. In this review, the role of PI3K pathway activation in thyroid cancer will be discussed, with a focus on recent advances. PMID:18502332

Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

PubMed Central

Di Sante, Gabriele; Pestell, Timothy G.; Casimiro, Mathew C.; Bisetto, Sara; Powell, Michael J.; Lisanti, Michael P.; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M.; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W.; Pestell, Richard G.

2016-01-01

Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD+-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1−/− cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD+-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

Dietary Supplementation with Fresh Pineapple Juice Decreases Inflammation and Colonic Neoplasia in IL-10-deficient Mice with Colitis

PubMed Central

Hale, Laura P.; Chichlowski, Maciej; Trinh, Chau T.; Greer, Paula K.

2010-01-01

Background Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of pro-inflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10−/− mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10−/− mice with chronic colitis as compared with bromelain derived from stem. Results Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 16 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (p = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% vs. 66%; p< 0.02), with fewer neoplastic lesions/colon (p = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. Conclusions These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease. PMID:20848493

Genetic Variants in TAP Are Associated with High-Grade Cervical Neoplasia

PubMed Central

Einstein, Mark H.; Leanza, Suzanne; Chiu, Lydia G.; Schlecht, Nicolas F.; Goldberg, Gary L.; Steinberg, Bettie M.; Burk, Robert D.

2018-01-01

Purpose The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms in TAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex ×MAP). HPV typing was done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (p = 0.01).The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer. PMID:19188174

The role of APC in WNT pathway activation in serrated neoplasia.

PubMed

Borowsky, Jennifer; Dumenil, Troy; Bettington, Mark; Pearson, Sally-Ann; Bond, Catherine; Fennell, Lochlan; Liu, Cheng; McKeone, Diane; Rosty, Christophe; Brown, Ian; Walker, Neal; Leggett, Barbara; Whitehall, Vicki

2018-03-01

Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively. WNT pathway activation was seen to a lesser extent in serrated pathway lesions. It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001). However, unlike the conventional pathway, truncating APC mutations were rare in the serrated pathway lesions especially sessile serrated adenomas even when dysplastic (15%) and in the BRAF mutant cancers with microsatellite instability that arise from them (8%). In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%). We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis. Moderate impact APC mutations and non-APC-related causes of increased WNT signaling may have a more important role in serrated neoplasia than the truncating APC mutations

Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer.

PubMed

Jung, Seung-Hyun; Shin, Sun; Kim, Min Sung; Baek, In-Pyo; Lee, Ji Youl; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-05-01

Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown. Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA. We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization. Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared. The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA ('common'), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were 'PCA-specific', suggesting their roles in HGPIN progression to PCA. The 8p loss was either 'common' or 'PCA-specific'. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied. HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression. In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Primary vulvar neoplasia: a review of in situ and invasive carcinoma, 1935-1972.

PubMed

Japaze, H; Garcia-Bunuel, R; Woodruff, J D

1977-04-01

This survey reports the past 38 years of experience with 192 cases of carcinoma of the vulva seen and treated at the Johns Hopkins Hospital. The review stresses the increased incidence of in situ neoplasia and the importance of individualization of therapy. Also the changing concepts in terminology (eg, the leukoplakic vulvitis of the past is the dystrophy of the present) suggest that the precursory alterations of previous discussions must be reviewed in the light of such an altered nomenclature. Features of epidemiologic and histologic importance are discussed.

[Practical problems in breast screening. Columnar cell lesions including flat epithelial atypia and lobular neoplasia].

PubMed

Nährig, J

2008-11-01

Columnar cell lesions (CCL) and lobular neoplasia (LN) are encountered with increasing frequency in breast screening biopsies. CCLs are frequently associated with microcalcifications, whereas LN is an incidental finding in most cases. Flat epithelia atypia (FEA) the atypical variant of CLL, LN and atypical ductal hyperplasia (ADH) are frequently associated lesions. Molecular genetic studies of CCL, ductal carcinoma in situ (DCIS) and low grade invasive carcinomas revealed similar chromosomal alterations supporting the assumption that CCLs are neoplastic proliferations. The frequent association of FEA together with well differentiated invasive carcinomas provides further evidence of this concept. There is no internationally accepted classification of CCLs at present. CDH1-gene mutations are the cardinal feature of LN and invasive lobular carcinoma. In immunohistochemically CDH1-positive cases, alternative genetic alterations of the CDH1 pathway can lead to functional loss of CDH1. In our opinion morphologically and immunohistochemically hybrid lesions may represent this group of lobular lesions. Recent follow-up data suggest a higher rate of ipsilateral carcinomas in patients with previously diagnosed LN. It is currently an open question whether FEA and LN are members of a common family of intralobular proliferations, which are non-obligatory precursors of a low nuclear grade breast neoplasia family.

Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

NASA Astrophysics Data System (ADS)

Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

2017-04-01

Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients

PubMed Central

Ionescu, EM; Nicolaie, T; Ionescu, MA; Becheanu, G; Andrei, F; Diculescu, M; Ciocirlan, M

2015-01-01

Rationale: DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. Objective: The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in “medium risk” individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). Methods and Results: We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were “medium risk” individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In “medium risk” individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in “medium risk” individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. Discussion: NDI score may have a role as a colorectal cancer-screening test in “medium risk” individuals. Abbreviations: DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non

Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

2016-02-01

Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

Rapid spontaneous regression of acute-onset vulvar intraepithelial neoplasia 3 in young women: a case series.

PubMed

Stephenson, Ruth D; Denehy, Thad R

2012-01-01

Vulvar intraepithelial neoplasia 3 (VIN 3)/vulvar carcinoma in situ is currently treated by surgical excision, laser ablation, or topically with 5-fluorouracil or imiquimod. The rate of progression of untreated VIN 3/vulvar carcinoma in situ to invasive cancer is significant, although difficult to assess, because most patients undergo treatment. The peak incidence of invasive carcinoma of the vulva occurs in the sixth decade, which may indicate that human papillomavirus (HPV)-related preinvasive disease in the younger population has a lower progression rate. However, the risk of invasive disease cannot be disregarded. This is a case series of complete spontaneous resolution of untreated VIN 3/vulvar carcinoma in situ in 5 healthy women aged 20 to 36 years from a single community gynecologic oncologist practice from 2006 to 2010. Complete spontaneous regression of acute VIN 3/vulvar carcinoma in situ was reported in 6 healthy young women aged 20 to 36 years. New sexual partners were reported in 2 of the 6 patients preceding the onset of vulvar lesions within 6 months. All patients were nonsmokers, healthy without known immunocompromise, and noted the acute onset of vulvar lesions. Vulvar intraepithelial neoplasia 3/vulvar carcinoma in situ was diagnosed on biopsy and confirmed on independent review. All lesions were multifocal in nature. Time to spontaneous regression was 6, 6, 8, 12, 18, and 20 weeks after initial biopsy. No patient received the HPV vaccine. Recurrence has not been noted in any of the patients within the follow-up period of 6 to 60 months. Short-term follow-up with conservative management of acute-onset VIN 3/vulvar carcinoma in situ in this young patient population correlates with similar treatment strategies for HPV-related cervical intraepithelial neoplasia of the cervix and may prevent disfigurement, pain, and complications associated with the current recommended therapeutic modalities. The timing of intervention for VIN 3/vulvar carcinoma in

A retrospective study of skull base neoplasia in 42 dogs.

PubMed

Rissi, Daniel R

2015-11-01

This study describes the prevalence and distribution of 42 cases of skull base neoplasia in dogs between 2000 and 2014. The average age of affected individuals was 9.5 years, and there was no sex or breed predisposition. The most common skull base neoplasms were meningioma (25 cases) and pituitary adenoma (9 cases). Less common tumors included craniopharyngioma (2 cases), nerve sheath tumor (2 cases), and 1 case each of pituitary carcinoma, meningeal oligodendrogliomatosis, presumed nasal or sinonasal carcinoma, and multilobular tumor of bone. All neoplasms caused some degree of compression of adjacent structures. The distribution of the tumors was greatest in the sellar region (n = 18), followed by the paranasal region (n = 12), caudal cranial fossa (n = 10), central cranial fossa (n = 1), and rostral cranial fossa (n = 1). © 2015 The Author(s).

Expression of the Tpl2/Cot oncogene in human T-cell neoplasias.

PubMed

Christoforidou, Anna V; Papadaki, Helen A; Margioris, Andrew N; Eliopoulos, George D; Tsatsanis, Christos

2004-12-03

Tpl2/Cot oncogene has been identified in murine T-cell lymphomas as a target of MoMuLV insertion. Animal and tissue culture studies have shown that Tpl2/Cot is involved in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production by T-cells contributing to T-cell proliferation. In the present report we examined a series of 12 adult patients with various T-cell malignancies, all with predominant leukemic expression in the periphery, for the expression of Tpl2/Cot oncogene in order to determine a possible involvement of Tpl2/Cot in the pathogenesis of these neoplasms. Our results showed that Tpl2/Cot was overexpressed in all four patients with Large Granular Lymphocyte proliferative disorders (LGL-PDs) but in none of the remaining eight patients with other T-cell neoplasias. Interestingly, three of the LGL-PD patients displayed neutropenia, one in association with sarcoidosis. Serum TNF-alpha levels were increased in all Tpl2/Cot overexpressing patients while serum IL-2 was undetectable in all subjects studied. Genomic DNA analysis revealed no DNA amplification at the Tpl2/Cot locus in any of the samples analyzed. We conclude that Tpl2/Cot, a gene extensively studied in animal and tissue culture T-cell models may be also involved in the development of human LGL-PD and may have a role in the pathogenesis of immune manifestations associated with these diseases. This is the first report implicating Tpl2/Cot in human T-cell neoplasias and provides a novel molecular event in the development of LGL-PDs.

Synchronous fluorescence spectroscopy of colon neoplasia

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Semyachkina-Glushkovskaya, Oxana; Genova, Tsanislava; Penkov, Nikolay; Terziev, Ivan; Vladimirov, Borislav; Avramov, Latchezar

2017-03-01

Synchronous fluorescence spectroscopy (SFS) is a steady-state approach that we used for evaluation of specific fluorescence characteristics of cancerous colorectal tissues. SFS allow narrowing of the fluorescence spectra received, which increase the spectral resolution and improve the analysis of the fluorescence origin in such complex objects, such as biological tissues. In our study we investigate the characteristic differences, with diagnostic meaning, in the synchronous fluorescence spectra (SFS) of cancerous and healthy colorectal tissues ex vivo using a spectrofluorimeter FluoroLog3 (HORIBA, JobinYvon, France) for obtaining of the SFS data in a broad spectral range (300-800 nm) using excitation in the range of 280-440 nm with a delta lambda between 0 and 200 nm with a 10 nm step between scanning excitation and emission data. The procedure of obtaining the investigated samples ex vivo includes their excision during surgery for removal of neoplasia lesions. After the surgical removal biological samples are transported in isothermal conditions and safekeeping solution from the hospital to the spectral laboratory, where their spectral properties were investigated. All patients received and signed written informed consent and this research is approved by Ethics committee of University Hospital "Tsaritsa Yoanna", Sofia. Histological analysis was used as "gold standard" for evaluation of tissue samples and comparison of the spectral data received.

A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process.

PubMed

Carr, Norman J; Cecil, Thomas D; Mohamed, Faheez; Sobin, Leslie H; Sugarbaker, Paul H; González-Moreno, Santiago; Taflampas, Panos; Chapman, Sara; Moran, Brendan J

2016-01-01

Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.

Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia.

PubMed

Long, Kevin C; Menon, Raman; Bastawrous, Amir; Billingham, Richard

2016-03-01

The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost-effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established.

Anal cancer and intraepithelial neoplasia screening: A review

PubMed Central

Leeds, Ira L; Fang, Sandy H

2016-01-01

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia

PubMed Central

Long, Kevin C.; Menon, Raman; Bastawrous, Amir; Billingham, Richard

2016-01-01

The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost–effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established. PMID:26929753

Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types

PubMed Central

Ekeowa-Anderson, A. L.; Harwood, C. A.; Perrett, C. M.; Sahota, A.; Annan, H.; Ran, H.; Leigh, I. M.; Gibbon, K. L.

2008-01-01

Summary Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple α and β papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited. PMID:17362236

Dietary supplementation with fresh pineapple juice decreases inflammation and colonic neoplasia in IL-10-deficient mice with colitis.

PubMed

Hale, Laura P; Chichlowski, Maciej; Trinh, Chau T; Greer, Paula K

2010-12-01

Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of proinflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10(-/-) mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with chronic colitis as compared with bromelain derived from stem. Colitis was triggered in Il10(-/-) mice by exposure to the non-steroidal anti-inflammatory drug piroxicam. Mice with colitis were supplemented with fresh vs. boiled pineapple juice or bromelain purified from stem for up to 6 months. Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 14 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (P = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% versus 66%; P < 0.02), with fewer neoplastic lesions/colon (P = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly

Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia.

PubMed

Marnach, Mary L; Butler, Kristina A; Henry, Michael R; Hutz, Catherine E; Langstraat, Carrie L; Lohse, Christine M; Casey, Petra M

2017-04-01

Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m 2 vs. 31 kg/m 2 ; p < 0.001). Among 332 women with follow-up endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometrial hyperplasia) resolved in 83% and 87% of patients, respectively (p = 0.31). Rates of resolution of EIN subcategory 2 (endometrial intraepithelial neoplasia) were also similar between groups (68% vs. 62%; p = 0.82). In women with EIN subcategory 3 (endometrial adenocarcinoma), 22% of those using LNG IUS and one of two women treated with OP had resolution of disease as of last follow-up. OP and LNG IUS offer similar endometrial protection for women with EIN. LNG IUS offers convenience, minimal adverse effects, reversibility, and long-term endometrial protection.

Is endoscopic forceps biopsy enough for a definitive diagnosis of gastric epithelial neoplasia?

PubMed

Lee, Chang Kyun; Chung, Il-Kwun; Lee, Suck-Ho; Kim, Sang Pil; Lee, Sae Hwan; Lee, Tae Hoon; Kim, Hong-Soo; Park, Sang-Heum; Kim, Sun-Joo; Lee, Ji-Hye; Cho, Hyun Deuk; Oh, Mee-Hye

2010-09-01

Endoscopic forceps biopsy (EFB) as the primary histological diagnosis of gastric epithelial neoplasia (GEN) is debated in the era of endoscopic resection (ER). Our aim was to investigate the diagnostic reliability of EFB in patients with GEN compared with ER specimens as the reference standard for the final diagnosis in a large consecutive series. This was a cross-sectional retrospective study at a tertiary-referral center. A total of 354 consecutive patients with 397 GENs underwent ER (endoscopic mucosal resection or endoscopic submucosal dissection). Discrepancy rates between the histological results from EFB and ER specimens were assessed. Discrepancies that could affect patient outcome or clinical care were considered major. The overall histological discrepancy rate between EFB and ER specimens was 44.5% (95% confidence interval [CI], 39.7-49.5%) among the enrolled patients. The overall discrepancy rate was significantly higher in the intraepithelial neoplasia (IEN) group than in the carcinoma group (49.8% vs 25.6%, P < 0.001). The major discrepancy rate was also significantly higher in the IEN group than in the carcinoma group (36.6% vs 7.0%, P < 0.001). In subgroup analysis of the IEN group, a major histological discrepancy rate of 33.6% (70/208) for low-grade and 42.7% (44/103) for high-grade IEN was found, respectively. Endoscopic forceps biopsy was insufficient for a definitive diagnosis and therapeutic planning in patients with GEN. ER should be considered as not only definitive treatment but also a procedure for a precise histological diagnosis for lesions initially assessed as GEN by forceps biopsy specimens.

Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia

USGS Publications Warehouse

Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

2009-01-01

Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

Clinical and Economic Value of p16INK4a for the Differential Diagnosis of Morphologic Cervical Intraepithelial Neoplasia 2.

PubMed

Fishkel, Vanina S; Monge, Fernando C; von Petery, Felicitas M; Tapper, Karen E; Peña, Teresa M; Torres, Florencia; Poletta, Fernando A; Elgart, Jorge F; Avagnina, Alejandra; Denninghoff, Valeria

2018-05-04

The detection of high-grade intraepithelial lesions requires highly sensitive and specific methods that allow more accurate diagnoses. This contributes to a proper management of preneoplastic lesions, thus avoiding overtreatment. The purpose of this study was to analyze the value of immunostaining for p16 in the morphologic assessment of cervical intraepithelial neoplasia 2 lesions, to help differentiate between low-grade (p16-negative) and high-grade (p16-positive) squamous intraepithelial lesions. The direct medical cost of the treatment of cervical intraepithelial neoplasia 2 morphologic lesions was estimated. A retrospective observational cross-sectional study was carried out. This study analyzed 46 patients treated with excisional procedures because of cervical intraepithelial neoplasia 2 lesions, using loop electrosurgical excision procedures. Immunostaining for the biomarker was performed. For the estimation of overtreatment, percentages (%) and their 95% confidence interval were calculated. Of the 41 patients analyzed, 32 (78%) showed overexpression of p16 and 9 (22%) were negative (95% confidence interval, 11%-38%). Mean follow-up was 2.9 years, using cervical cytology testing (Pap) and colposcopy. High-risk human papillomavirus DNA tests were performed in 83% of patients. These retrospective results reveal the need for larger biopsy samples, which would allow a more accurate prediction of lesion risk. Considering the cost of p16 staining, and assuming the proper management of the low-grade lesion, an average of US$919 could be saved for each patient with a p16-negative result, which represents a global direct cost reduction of 10%.

Xeroderma pigmentosum with bilateral ocular surface squamous neoplasia and review of the literature

PubMed Central

Kalamkar, Charudutt; Radke, Nishant; Mukherjee, Amrita; Radke, Snehal

2016-01-01

Xeroderma pigmentosum is a rare genetic disorder associated with various ocular malignancies. Here we report a single paediatric case of xeroderma pigmentosum with bilateral ocular surface squamous neoplasia (OSSN) presenting with diffuse lesion in one eye and a large mass in the other eye. Diffuse OSSN in one eye was treated with topical chemotherapy using mitomycin-C (0.04%) and the large OSSN in the other eye was treated with a combination of surgery and topical chemotherapy. Long-term follow-up and a multimodality treatment approach are necessary to identify and manage recurrences of OSSN in XP. PMID:27166000

Xeroderma pigmentosum with bilateral ocular surface squamous neoplasia and review of the literature.

PubMed

Kalamkar, Charudutt; Radke, Nishant; Mukherjee, Amrita; Radke, Snehal

2016-05-10

Xeroderma pigmentosum is a rare genetic disorder associated with various ocular malignancies. Here we report a single paediatric case of xeroderma pigmentosum with bilateral ocular surface squamous neoplasia (OSSN) presenting with diffuse lesion in one eye and a large mass in the other eye. Diffuse OSSN in one eye was treated with topical chemotherapy using mitomycin-C (0.04%) and the large OSSN in the other eye was treated with a combination of surgery and topical chemotherapy. Long-term follow-up and a multimodality treatment approach are necessary to identify and manage recurrences of OSSN in XP. 2016 BMJ Publishing Group Ltd.

Intraepithelial and invasive neoplasia of the vulva in association with human papillomavirus infection.

PubMed

Planner, R S; Hobbs, J B

1988-06-01

Colposcopic examination of 335 women with cytologically detected human papillomavirus (HPV) revealed involvement of the cervix in 316 patients (94%), vagina in 276 (82%) and vulva in 148 (44%). A symptom complex of pruritus and superficial dyspareunia was found in 98 of the 148 patients with vulvar infection (66%). Histologic examination revealed HPV-associated vulvar intraepithelial neoplasia (VIN) in 11 of 148 biopsies (7.4%). Follow-up of the patients with HPV infection with or without VIN showed a spontaneous regression rate of 56% but also demonstrated progression to VIN 3 in two patients and to invasive carcinoma of the vulva in one.

Endoscopic diagnosis and treatment of early esophageal squamous neoplasia

PubMed Central

Shimamura, Yuto; Ikeya, Takashi; Marcon, Norman; Mosko, Jeffrey D

2017-01-01

Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality. It carries a poor prognosis as more than half of patients present with advanced and unresectable disease. One contributing factor is the increased risk of lymph node metastases at early stages of disease. As such, it is essential to detect squamous cell neoplasia (SCN) at an early stage. In order to risk stratify lesions, endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol’s chromoendoscopy. The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment. Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use. Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time. Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN. PMID:28979708

Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

PubMed Central

Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

2012-01-01

We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present. PMID:24213321

Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy.

PubMed

van Esch, Edith M G; Welters, Marij J P; Jordanova, Ekaterina S; Trimbos, J Baptist M Z; van der Burg, Sjoerd H; van Poelgeest, Mariëtte I E

2012-07-01

Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.

Intracellular signaling entropy can be a biomarker for predicting the development of cervical intraepithelial neoplasia.

PubMed

Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

2017-01-01

While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology, a prospective study). From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia.

Intracellular signaling entropy can be a biomarker for predicting the development of cervical intraepithelial neoplasia

PubMed Central

Sato, Masakazu; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

2017-01-01

While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology, a prospective study). From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia. PMID:28453530

Outcome of accelerated radiotherapy alone or accelerated radiotherapy followed by exenteration of the nasal cavity in dogs with intranasal neoplasia: 53 cases (1990-2002).

PubMed

Adams, William M; Bjorling, Dale E; McAnulty, Jonathan E; Green, Eric M; Forrest, Lisa J; Vail, David M

2005-09-15

To compare long-term results of radiotherapy alone versus radiotherapy followed by exenteration of the nasal cavity in dogs with malignant intranasal neoplasia. Retrospective study. 53 dogs with malignant intranasal neoplasia. All dogs underwent radiotherapy consisting of administration of 10 fractions of 4.2 Gy each on consecutive weekdays. For dogs in the surgery group (n=13), follow-up computed tomography was performed, and dogs were scheduled for surgery if persistent or recurrent tumor was seen. Perioperative complications for dogs that underwent surgery included hemorrhage requiring transfusion (2 dogs) and subcutaneous emphysema (8). Rhinitis and osteomyelitis-osteonecrosis occurred significantly more frequently in dogs in the radiotherapy and surgery group (9 and 4 dogs, respectively) than in dogs in the radiotherapy-only group (4 and 3 dogs, respectively). Two- and 3-year survival rates were 44% and 24%, respectively, for dogs in the radiotherapy group and 69% and 58%, respectively, for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (477 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months). Results suggest that exenteration of the nasal cavity significantly prolongs survival time in dogs with intranasal neoplasia that have undergone radiotherapy. Exenteration after radiotherapy may increase the risk of chronic complications.

Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

PubMed

Kuroki, Lindsay M; Frolova, Antonina I; Wu, Ningying; Liu, Jingxia; Powell, Matthew; Thaker, Premal H; Massad, L Stewart

2017-07-01

The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

Multiple endocrine neoplasia type 1

PubMed Central

Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

2006-01-01

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

Remitting seronegative symmetrical synovitis with pitting edema syndrome: followup for neoplasia.

PubMed

Russell, Elizabeth B

2005-09-01

To investigate whether the remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome may represent a paraneoplastic disorder in a significant percentage of cases. Patients diagnosed with RS3PE syndrome at the Medical College of Wisconsin before 1995 were telephoned and asked about their rheumatologic course since initial diagnosis of RS3PE and whether they had been diagnosed with any cancer. If so, permission was obtained to review tissue pathology. Criteria used for diagnosis of RS3PE syndrome included sudden onset of painful diffuse swelling of both hands associated with pitting edema of the dorsa of the hands without other synovitis or evidence of disease, negative rheumatoid factor, absence of radiologic abnormalities, and resolution within 6-12 months without sequelae. Data from the national SEER databank on population incidence of cancers in the appropriate sex, age, and ethnic groups for the years under study were used to assess relative risk for cancer. There were 10 patients for whom followup data were available. Four had a cancer diagnosed following recognition of the RS3PE syndrome; 1 patient developed non-Hodgkin's lymphoma initially diagnosed as hairy cell leukemia after 4 years; 1 developed acute lymphocytic leukemia with hyperdiploidy after 14 years; 1 was diagnosed with male breast cancer after 2.5 years; and 1 developed squamous cell lung cancer 12 months after RS3PE diagnosis. SEER data project an estimated rate of 2-3 cancers in a similar group of 10 patients of the same sex, age, and time period for this geographic area. The small sample size in this longterm followup precludes extrapolation to larger populations but suggests that there may be a slightly higher than expected rate of neoplasia in patients diagnosed with RS3PE syndrome. The interval between onset of RS3PE syndrome and diagnosis of cancer was fairly long, indicating that patients should be monitored for neoplasia with prudent age and sex specific surveillance

Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva.

PubMed

Rakislova, Natalia; Alemany, Laia; Clavero, Omar; Del Pino, Marta; Saco, Adela; Quirós, Beatriz; Lloveras, Belen; Alejo, Maria; Halec, Gordana; Quint, Wim; de Sanjosé, Silvia; Ordi, Jaume

2018-06-01

Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC.

Epithelial neoplasia coincides with exacerbated injury and fibrotic response in the lungs of Gprc5a-knockout mice following silica exposure

PubMed Central

Zhong, Shuangshuang; Song, Hongyong; Sun, Beibei; Zhou, Binhua P.; Deng, Jiong; Han, Baohui

2015-01-01

Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a−/− mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a−/− mouse model following silica exposure. Intra-tracheal administration of fine silica particles in Gprc5a−/− mice resulted in more severe lung injury and pulmonary inflammation than in wild-type mice. Moreover, an enhanced fibrogenic response, including EMT-like characteristics, was induced in the lungs of Gprc5a−/− mice compared to those from wild-type ones. Importantly, increased hyperplasia or neoplasia coincided with silica-induced tissue injury and fibrogenic response in lungs from Gprc5a−/− mice. Consistently, expression of MMP9, TGFβ1 and EGFR was significantly increased in lungs from silica-treated Gprc5a−/− mice compared to those untreated or wild-type ones. These results suggest that, the process of tissue repair coincides with tissue damages; whereas persistent tissue damages leads to abnormal repair or neoplasia. Thus, silica-induced pulmonary inflammation and injury contribute to increased neoplasia development in lungs from Gprc5a−/− mouse model. PMID:26447616

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers.

PubMed

Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise; Jørgensen, Lars N; Madsen, Mogens R; Vilandt, Jesper; Hillig, Thore; Klaerke, Michael; Nielsen, Knud T; Laurberg, Søren; Brünner, Nils; Gawel, Susan; Yang, Xiaoqing; Davis, Gerard; Heijboer, Annemieke; Martens, Frans; Nielsen, Hans J

2017-03-15

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC. © 2016 UICC.

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

PubMed Central

Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

2017-01-01

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway. PMID:27885175

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway.

PubMed

Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

2017-01-15

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.

Intratubular Germ Cell Neoplasia of the Testis, Bilateral Testicular Cancer, and Aberrant Histologies.

PubMed

Sharma, Pranav; Dhillon, Jasreman; Sexton, Wade J

2015-08-01

Intratubular germ cell neoplasia (ITGCN) is a precursor lesion for testicular germ cell tumors, most of which are early stage. ITGCN is also associated with testicular cancer or ITGCN in the contralateral testis, leading to a risk of bilateral testicular malignancy. Testicular biopsy detects most cases, and orchiectomy is the treatment of choice in patients with unilateral ITGCN. Low-dose radiation therapy is recommended in patients with bilateral ITGCN or ITGCN in the solitary testis, but the long-term risks of infertility and hypogonadism need to be discussed with the patient. Rare histologies of primary testicular cancer are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Neoplasia Driven by Mutant c-KIT Is Mediated by Intracellular, Not Plasma Membrane, Receptor Signaling▿

PubMed Central

Xiang, Zhifu; Kreisel, Frederike; Cain, Jennifer; Colson, AnnaLynn; Tomasson, Michael H.

2007-01-01

Activating mutations in c-KIT are associated with gastrointestinal stromal tumors, mastocytosis, and acute myeloid leukemia. In attempting to establish a murine model of human KITD816V (hKITD816V)-mediated leukemia, we uncovered an unexpected relationship between cellular transformation and intracellular trafficking. We found that transport of hKITD816V protein was blocked at the endoplasmic reticulum in a species-specific fashion. We exploited these species-specific trafficking differences and a set of localization domain-tagged KIT mutants to explore the relationship between subcellular localization of mutant KIT and cellular transformation. The protein products of fully transforming KIT mutants localized to the Golgi apparatus and to a lesser extent the plasma membrane. Domain-tagged KITD816V targeted to the Golgi apparatus remained constitutively active and transforming. Chemical inhibition of intracellular transport demonstrated that Golgi localization is sufficient, but plasma membrane localization is dispensable, for downstream signaling mediated by KIT mutation. When expressed in murine bone marrow, endoplasmic reticulum-localized hKITD816V failed to induce disease in mice, while expression of either Golgi-localized HyKITD816V or cytosol-localized, ectodomain-deleted KITD816V uniformly caused fatal myeloproliferative diseases. Taken together, these data demonstrate that intracellular, non-plasma membrane receptor signaling is sufficient to drive neoplasia caused by mutant c-KIT and provide the first animal model of myelomonocytic neoplasia initiated by human KITD816V. PMID:17060458

Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett's esophagus

NASA Astrophysics Data System (ADS)

Muldoon, Timothy J.; Thekkek, Nadhi; Roblyer, Darren; Maru, Dipen; Harpaz, Noam; Potack, Jonathan; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2010-03-01

Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barrett's esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected fresh tissue was imaged with fiber bundle microendoscopy; images were analyzed by visual interpretation or by quantitative image analysis to predict whether the imaged sites were non-neoplastic or neoplastic. The best performing pair of quantitative features were chosen based on their ability to correctly classify the data into the two groups. Predictions were compared to the gold standard of histopathology. Subjective analysis of the images by expert clinicians achieved average sensitivity and specificity of 87% and 61%, respectively. The best performing quantitative classification algorithm relied on two image textural features and achieved a sensitivity and specificity of 87% and 85%, respectively. This ex vivo pilot trial demonstrates that quantitative analysis of images obtained with a simple microendoscope system can distinguish neoplasia in Barrett's esophagus with good sensitivity and specificity when compared to histopathology and to subjective image interpretation.

The Natural History of Neoplasia

PubMed Central

Pitot, Henry C.

1977-01-01

The stages of initiation and promotion in the natural history of epidermal carcinogenesis have been known for many years. Recently, experimental systems other than skin have been shown to exhibit similar, if not completely analogous, stages in the natural history of neoplasia. In particular, the demonstration by Peraino and his associates that phenobarbital may enhance the production of hepatomas by a relatively subcarcinogenic dose of acetylaminofluorene was one of the first demonstrations of stages occurring in an extraepidermal neoplasm. Studies reported in this paper have demonstrated that administration of phenobarbital (0.05% in the diet) for 6 months following a single dose of diethylnitrosamine (5 to 10 mg/kg) given within 24 hours after partial hepatectomy resulted in a marked increase in the number of enzyme-altered foci in the liver as well as in the production of hepatocellular carcinomas. This was compared to animals receiving only a single dose of diethylnitrosamine following partial hepatectomy with no further treatment, in which only a relatively small number of foci were evident in the absence of phenobarbital feeding. Using three different enzyme markers, a distinct degree of phenotypic heterogeneity of the enzyme-altered foci in liver was demonstrated. These studies have shown that liver carcinogensis can be readily divided into two stages: a) initiation by a single dose of diethylnitrosamine following partial hepatectomy and b) promotion by the continuous feeding of phenobarbital. Furthermore, the immediate progeny of the initiated cells, the enzyme-altered focus, may be recognized by suitable microscopic means prior to the formation of gross lesions as required in the skin system. These initiated cell populations exhibit a degree of biochemical heterogeneity which reflects that seen in fully developed hepatic neoplasms, suggesting that promotion and progression in this system does not significantly alter the basic biochemical characteristics of

Altered gene expression patterns during the initiation and promotion stages of neonatally diethylstilbestrol-induced hyperplasia/dysplasia/neoplasia in the hamster uterus.

PubMed

Hendry, William J; Hariri, Hussam Y; Alwis, Imala D; Gunewardena, Sumedha S; Hendry, Isabel R

2014-12-01

Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: (1) immunoblot analyses and (2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and (3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: (1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and (2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: correlation with primary tumor size.

PubMed

Lowney, J K; Frisella, M M; Lairmore, T C; Doherty, G M

1998-12-01

Islet cell tumor (ICT) metastasis is one of the potentially lethal outcomes of multiple endocrine neoplasia type 1 (MEN 1). Management of ICT in patients with MEN 1 is controversial; some advocate resection based on biochemical evidence of progression, whereas others use tumor size to predict the risk of metastasis and the need for resection. This study correlates the size of primary ICT with the presence of metastases. Forty-eight patients with MEN 1 with ICT, from 34 kindreds followed up in our multiple endocrine neoplasia program, were evaluated; 43 of the 48 have been explored for ICT. Metastases to the lymph nodes and liver were documented. Thirty-three percent of patients with pancreatic tumors less than 1 cm in greatest diameter had metastatic disease at surgery and in follow-up, whereas 34.8% of patients with tumors greater than 2 cm in diameter had metastases to lymph nodes or liver. The 2 patients with liver metastases each had primary tumors greater than 2 cm. Follow-up revealed subsequent metastasis in 1 patient. The size of primary tumors in MEN 1 does not correlate with metastatic potential. This is not a good criterion for exploration. Continued follow-up of these patients will be necessary to define the effect of operation on the course of ICT in MEN 1.

Comparing Benign and Malignant Neoplasia and DSB Induction for Low-and High-LET Radiation

NASA Astrophysics Data System (ADS)

Burns, Fredric; Tang, Moon-Shong Eric; Wu, Feng

One-and 2-stage models based on DNA double strand breaks (DSBs) have been developed to describe the dose and LET dependence of cancer induction in rat skin exposed to the Bragg plateau of several ion beams or electron radiation. Data are presented showing that carcinomas (malignant) and fibromas (benign) are induced differently by low and high LET radiation. DSBs are subject to complex repair processes, including homologous and non-homologous end joining, that slowly eliminate broken chromosome ends but at the expense of elevating genomic instability that increases the risk of neoplasia. In this formulation the initial molecular lesion in radiation carcinogenesis is assumed to be a DNA double strand break (DSB). The 2-event model assumes that pairs of DSBs join to create cellular genomic instability that eventually progresses to malignancy. The 1-event model assumes that joining is insignificant but that unrepaired DSBs remain and are sufficiently destabilizing to produce low-grade neoplasias. The respective expected relationships between neoplasia yield (Y), radiation dose (D) and LET (L) are: Y(D) = CLD + BD2 (A) for 2-events and Y(D) = CLD (B) for 1-event. Respective B and C values have been evaluated empirically for carcinomas, fibromas and DSBs, the latter via the -H2Ax technique in surrogate keratinocytes, for several types of radiations, including, 40Ar ions, 56Fe ions, 20Ne ions, protons, electrons and x-rays. Fibromas outnumber carcinomas by about 6:1 but are more sensitive than carcinomas to the cytolethal effect of the radiations. The 2-event model agrees well with carcinoma yields in rat skin but fails to model fibromas correctly. Instead the fibroma yields best fitted with the 1-event model for the high LET ion radiations, but at very low LET (electron radiation), an empirical D3 component becomes apparent which is not currently incorporated into the theoretical model. At higher LET values, the D3 component was not detected. The overall results are

Lymphoma in pregnancy initially diagnosed as vaginal intraepithelial neoplasia and lichen planus.

PubMed

Nguyen, Thuong-Thuong; Gubens, Matthew; Arber, Daniel A; Advani, Ranjana; Juretzka, Margrit; Aziz, Natali

2011-08-01

Non-Hodgkin's lymphoma presenting as a vaginal mass in pregnancy is uncommon. A 38-year-old primigravid woman presented at 27 weeks of gestation with vaginal lesions, bleeding, and discharge. Previous vaginal biopsies had been consistent with vaginal intraepithelial neoplasia 1 and lichen planus. After admission for this enlarging vaginal mass and bleeding, she was noted to have a newly palpable breast mass. Biopsy of the breast mass and subsequent re-evaluation of original vaginal biopsies were consistent with diffuse large B-cell lymphoma. She was treated with chemoimmunotherapy during pregnancy and delivered a viable neonate at term. Although benign vaginal conditions are common, non-Hodgkin's lymphoma should be considered in the differential diagnosis of persistent or enlarging vaginal lesions in pregnancy.

Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

PubMed

Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

2017-05-01

We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

[New histological terminology of vulvar intraepithelial neoplasia].

PubMed

Bergeron, C

2008-01-01

The International Society for the Study of Vulvar Disease (ISSVD) recommends not to use a grading any more and to include in the term vulvar intraepithelial neoplasia (VIN), usual type, the previously called VIN 2 where the nuclear atypia and mitotic figures are confined to the basal half of the epithelium and VIN 3 where nuclear abnormalities and abnormal mitotic figures are present throughout most or all of the thickness of the epithelium. VIN, usual type, is related to a human papillomavirus (HPV) high-risk type infection in most of the cases. The histologic changes previously encompassed within the term VIN 1 will be described as flat condyloma or HPV effect. The less common type of VIN lesion is termed VIN, differentiated type, previously called "high grade" differentiated type or VIN simplex type. This type of VIN is a highly differentiated lesion. The atypia is confined to the basal and parabasal layers of the epithelium, where the cells have abundant cytoplasm and form abortive pearls and the nuclei are relatively uniform in size and contain coarse chromatin and prominent nucleoli. The epithelium does not contain koilocytosis because it is not associated with HPV. It is seen primarily in older women, with a previous history of lichen sclerosus. The diagnosis is often made late in association with keratinising squamous cell carcinomas.

THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

EPA Science Inventory

The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats

Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-
Mendel rat when administered either by corn oil gavage or in drin...

The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

PubMed

Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

2016-03-15

The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. © 2015 UICC.

Differentiated intraepithelial neoplasia of the vulva.

PubMed

Mulvany, Nicholas J; Allen, David G

2008-01-01

We present the clinical and pathological findings of 6 women with intraepithelial neoplasia of differentiated or simplex type (DVIN). The mean age was 68 years (range 55-82). One lesion was still in situ, whereas 5 were associated with squamous carcinoma, 4 of well-differentiated keratinizing type and 1 of poorly differentiated spindle-cell type. The invasive depth of the squamous carcinomas ranged from 0.6 to 8 mm and the surgical margins of all of the resection specimens were uninvolved by neoplastic cells. In contrast, DVIN involved the surgical margins in 5 specimens while the remaining specimen had normal surgical margins. In all 6 vulvar specimens, DVIN showed intense immunoreactivity for Ki-67 in the basal and parabasal cells while only 4 specimens showed reactivity for p53. In 5 surgical specimens with DVIN the number of CD1a cells was increased but little if any immunoreactivity could be found amongst the corresponding invasive neoplastic cells. Four squamous carcinomas also showed diffuse p53 reactivity. There was little difference in the pattern of Ki-67 expression between DVIN and squamous carcinoma. For a number of reasons, DVIN present diagnostic difficulty and considerable interobserver variation also exists. Our study suggests that Ki-67 and p16 are useful for distinguishing DVIN and classical VIN 3, whereas p53 and CD1a are useful for distinguishing DVIN and invasive squamous carcinoma. Furthermore, p53 appears to have higher specificity than sensitivity for distinguishing DVIN from normal squamous epithelium.

Cryotherapy treatment for cervical intraepithelial neoplasia: women's experiences in Peru.

PubMed

Coffey, Patricia S; Bingham, Allison; Winkler, Jennifer L; Bishop, Amie; Sellors, John W; Lagos, Gloria; Pastor, Cesar Moron

2005-01-01

Our objective was to examine cryotherapy experiences among women who received treatment for cervical intraepithelial neoplasia in a cervical cancer prevention project in rural Peru. The sample consisted of all women receiving cryotherapy during a 4-month period (July through October 2001). Structured interviews were conducted to collect information about the adequacy of information provision, women's satisfaction with cryotherapy, their ability to comply with postcryotherapy recommendations and condom use, their experience with cryotherapy side effects, and their satisfaction with cryotherapy follow-up. Of the 224 women who were interviewed, user satisfaction with cryotherapy treatment was generally good. A few women engaged in sex earlier than 30 days after treatment, primarily due to partner pressure to resume sex and the women's inability to successfully negotiate abstention from sex. These couples were not always able to use condoms. The percentage of women reporting vaginal discharge was within the range of responses reported in other studies. Cryotherapy appears to be acceptable to women in low-resource settings such as Peru.

Intraocular ALλ amyloidoma with plasma cell neoplasia in a cat.

PubMed

Kershaw, Olivia; Linek, Jens; Linke, Reinhold P; Gruber, Achim D

2011-09-01

An 11-year-old, neutered male domestic short-hair cat was presented with buphthalmos of the right eye and diagnosed with advanced glaucoma. Sonographic examination revealed an iridial thickening. Neoplasia was suspected and an enucleation was performed. Histopathology of the enucleated eye revealed abundant amyloid deposition predominantly in the anterior uveal tract accompanied by few to moderate numbers of well-differentiated plasma cells. The amyloid deposits were identified by staining with Congo red and showing green birefringence under polarized light. Immunohistochemically, amyloid and plasma cells stained intensely only with anti-ALλ antibody, supporting the amyloid tumor being an immunoglobulin-λ-light chain origin. Additional abnormalities included narrowing of the filtration angle and collapse of the ciliary cleft, and trabecular meshwork. One year post-enucleation, the cat was still healthy without signs of systemic amyloidosis or apparent metastatic disease. This is the first report of a cat with noncutaneous extramedullary plasmacytoma originating in the anterior uveal tract with resulting local amyloid. © 2011 American College of Veterinary Ophthalmologists.

Pulmonary preinvasive neoplasia.

PubMed

Kerr, K M

2001-04-01

Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour

p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias.

PubMed

Riethdorf, Sabine; Neffen, Eduardo F; Cviko, Aida; Löning, Thomas; Crum, Christopher P; Riethdorf, Lutz

2004-12-01

Up-regulation of p16INK4A is associated with high-risk human papillomavirus (HPV) in preinvasive and invasive cervical neoplasia. However, its expression in vulvar carcinomas, which have a diverse pathogenesis, has not been extensively studied. One hundred seventy-seven vulvar intraepithelial neoplasms (VIN), squamous cell carcinomas (SCC), and benign squamous epithelia were analyzed for p16 expression. RNA/RNA in situ hybridization was used to detect HPV 16 E6/E7 transcripts in 112. Ninety-five percent of VIN 3 and basaloid or warty SCCs (76/80) and 4% of keratinizing SCC (2/48) were moderately to strongly immunopositive for p16, which localized to nucleus and cytoplasm; 52/58 analyzed (90%) contained HPV 16 transcripts. The positive predictive value (PPV) of moderate to strong diffuse p16 immunostaining and HPV positivity for the diagnosis of VIN 3 and of basaloid or warty SCC was 97% and 95%, respectively. Conversely, 94% of keratinizing SCC contained heterogeneous staining, and when present, it was strictly cytoplasmic and frequently localized to the cells at the epithelial-stromal interface. Benign squamous epithelia were p16 negative, with the exception of lichen sclerosus, which contained focal and heterogeneously p16 positive in 42%. As in the cervix, intense diffuse p16 expression supports an HPV-related neoplastic process in vulvar neoplasia, irrespective of the level of differentiation. Up-regulation of p16 at the epithelial-stromal interface in HPV negative keratinizing SCCs is consistent with an HPV-independent response to alterations associated with invasion. These disparate patterns of p16 expression underscore 2 different mechanisms for p16 expression in HPV-related and HPV-unrelated vulvar carcinomas.

Frequency of invasive cancer in surgically excised vulvar lesions with intraepithelial neoplasia (VIN 3).

PubMed

Husseinzadeh, N; Recinto, C

1999-04-01

The aim of this study was to determine the frequency of invasive cancer found from specimens removed by surgical excision on patients with diagnosis of VIN 3. Seventy-eight patients with biopsy-proven vulvar intraepithelial neoplasia 3 (VIN 3) were treated by surgical excision. Sixteen patients (20.5%) were found to have invasion in the excised surgical specimen. Superficial invasion was seen in 7 patients (9%), 9 were noted to have >1 mm invasion (11.5%), and 1 patient had in situ Paget's disease (1.3%). Surgical excision should be considered a preferable method in management of patients with VIN 3. Copyright 1999 Academic Press.

Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

NASA Astrophysics Data System (ADS)

Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

2016-03-01

The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

Altered peptidase activities in thyroid neoplasia and hyperplasia.

PubMed

Larrinaga, Gorka; Blanco, Lorena; Errarte, Peio; Beitia, Maider; Sanz, Begoña; Perez, Itxaro; Irazusta, Amaia; Sánchez, Clara E; Santaolalla, Francisco; Andrés, Leire; López, José I

2013-01-01

Papillary thyroid carcinoma (PTC), follicular thyroid adenoma (FTA), and thyroid nodular hyperplasia (TNH) are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26) in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP), alanyl aminopeptidase (AlaAP), prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.

Neoplasia in ferrets: eleven cases with a review.

PubMed

Dillberger, J E; Altman, N H

1989-02-01

Records from a veterinary diagnostic laboratory in south Florida, U.S.A. were reviewed for cases of neoplasia in pet ferrets. Twelve ferret tumours were received over a four-year period; one case, a ferret with lymphocytic leukaemia and multi-organ involvement, had been reported previously. The other eleven tumours were: two chordomas of the tail, two sebaceous adenomas of the skin, a sebaceous epithelioma of the skin, a cutaneous mastocytoma, a malignant fibrous histiocytoma from the eyelid, a malignant mesenchymoma and an undifferentiated sarcoma from the dorsal abdominal cavity, a leiomyosarcoma found unattached in the abdominal cavity and an interstitial cell tumour of the testicle. A review of the literature yielded reports of 83 other tumours in domestic ferrets, black-footed ferrets and European polecats. Of the 95 ferret tumours, 46 were considered malignant. Tumours occurred in all organ systems except the respiratory tract and central nervous system. Affected ferrets ranged in age from 209 days to 12 years. The most frequently occurring tumours were ovarian stromal tumours (24 of 95), haemangiomas/haemangio-sarcomas (15 of 95). This information indicates that, contrary to previous opinion, ferrets appear to be subject to a similar incidence and variety of tumours as other animals.

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Transmission of hemic neoplasia in the bay mussel, Mytilus edulis, using whole cells and cell homogenate.

PubMed

Elston, R A; Kent, M L; Drum, A S

1988-01-01

Experimental studies with hemic neoplasia in the bay mussel indicated that the condition can be transmitted allogeneically with intact whole cells and cell-free homogenate. A differential pathogenesis of the disease in mussels receiving the two different inocula supports the argument that actual cell transplantation occurred. In addition to the first demonstration of the infectious nature of the disease with cell-free homogenates, it was also shown that the disease is transmitted by cohabitation. Remission of the disease occurred in some mussels indicating individual variation in recognition mechanisms.

Microbiota and innate immunity in intestinal inflammation and neoplasia.

PubMed

Cario, Elke

2013-01-01

This review focuses on recent advances and novel insights into the mechanistic events that may link commensal microbiota and host innate immunity in the pathophysiology of intestinal inflammation and neoplasia. Unanswered questions are discussed and future perspectives in the field are highlighted. Commensal microbiota, host innate immunity, and genetics form a multidimensional network that controls homeostasis of the mucosal barrier in the intestine. Large-scale sequencing projects have begun to catalog the healthy human microbiome. Converging evidence suggests that alterations in the regulation of the complex host environment [e.g., dysbiosis and overgrowth of select commensal bacterial species, dietary factors, copresence of facultative pathogens (including viruses), and changes in mucus characteristics] may trigger aberrant innate immune signaling, thereby contributing to the development of intestinal inflammation and associated colon cancer in the susceptible individual. Genetically determined innate immune malfunction may create an inflammatory environment that promotes tumor progression (such as the TLR4-D299G mutation). The next challenging steps to be taken are to decipher changes in the human microbiome (and virome) during well defined diseased states, and relate them to intestinal mucosal immune functions and host genotypes.

[Heredity in renal and prostatic neoplasia].

PubMed

Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

1997-09-01

There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of

Biologic behavior of vulvar intraepithelial neoplasia. Histologic and clinical parameters.

PubMed

Barbero, M; Micheletti, L; Preti, M; Valentino, M C; Nicolaci, P; Canní, M; Ghiringhello, B; Borgno, G

1993-02-01

The aim of this study was to evaluate the role by which different factors, such as human papillomavirus (HPV) infection, age, dystrophic alterations, focal nature and size of the lesion, influence the biologic behavior of vulvar intraepithelial neoplasia (VIN). Sixty-nine cases of VIN were investigated (28 VIN 1, 9 VIN 2, 32 VIN 3). Follow-up was possible in 58 cases, with a mean of 31 months; no treatment was given to 3 patients, while 55 were treated either medically or surgically. Eighty-four percent of the patients were cured, recurrences were found in 11%, and 5% of the patients showed progression of the disease to carcinoma. The ratio between medical and surgical treatment was the same among the cured, recurred and progressed groups of patients. No differences with regard to focal nature of the lesion, presence of HPV infection or dystrophic alterations were observed between the three groups of patients. Only the mean age was higher in patients who showed progression of the lesion to carcinoma.

Type I interferons modulate methotrexate resistance in gestational trophoblastic neoplasia.

PubMed

Elias, Kevin M; Harvey, Richard A; Hasselblatt, Kathleen T; Seckl, Michael J; Berkowitz, Ross S

2017-06-01

Resistance to methotrexate is a leading clinical problem in gestational trophoblastic neoplasia (GTN), but there are limited laboratory models for this condition. We created isogenic trophoblastic cell lines resistant to methotrexate and compared these to the parent cell lines using gene expression microarrays and qRT-PCR followed by mechanistic studies using recombinant cytokines, pathway inhibitors, and patient sera. Gene expression microarrays and focused analysis by qRT-PCR revealed methotrexate led to type I interferon upregulation, in particular interferon alpha 2 (IFNA2), and methotrexate resistance was associated with chronic low level increases in type I interferon expression. Recombinant IFNA2 imparted chemosensitive choriocarcinoma cells with partial resistance to methotrexate, while chemoresistant choriocarcinoma cells were uniquely sensitive to fludarabine, a STAT1 inhibitor. In pre-treatment patient sera, IFNA2 levels correlated with subsequent resistance to methotrexate chemotherapy. Methotrexate resistance is influenced by type I interferon signaling with prognostic and therapeutic implications for treating women with GTN. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

PubMed Central

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-01-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

PubMed

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-09-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more

Parathyroid surgical failures with sufficient decline of intraoperative parathyroid hormone levels: unobserved multiple endocrine neoplasia as an explanation.

PubMed

Westerdahl, Johan; Bergenfelz, Anders

2006-06-01

A sufficient decline in levels of parathyroid hormone measured intraoperatively (ioPTH) precludes early and late surgical failures. A case series of consecutive patients undergoing parathyroidectomy with ioPTH measurement. A university hospital. Two hundred sixty-nine consecutive patients with sporadic primary hyperparathyroidism who underwent first-time parathyroid surgery with ioPTH measurement were followed up for as long as 10 years after surgery. Data on all patients have been collected in a prospective database. Surgical failures up to 10 years after parathyroid surgery. With an average follow-up of 3.6 years (range, 6-120 months), the overall cure rate was 96%. The ioPTH level correctly predicted long-term outcome in 248 (92%) of 269 patients. Six patients had a false-positive ioPTH finding. Five of these patients were found to have germline mutations in the gene for multiple endocrine neoplasia. The remaining patient has not undergone genetic testing. The mutations have rarely (n = 1) or never (n = 4) been described before, to our knowledge. Intraoperative measurement of PTH level has a high overall accuracy with a mean follow-up of 3.6 years. However, among the late surgical failures with false-positive ioPTH findings, overlooked mutations in the multiple endocrine neoplasia gene should be suspected, and therefore genetic analyses in these patients are of great importance.

Alopecia universalis in a dog with testicular neoplasia.

PubMed

Outerbridge, Catherine A; White, Stephen D; Affolter, Verena K

2016-12-01

To describe a case of testicular neoplasia and alopecia universalis in a dog, and successful treatment of the latter with ciclosporin. Twelve-year-old intact male wirehaired fox terrier. Castration, skin biopsy for histopathology, lymphocyte immunophenotyping and clonality analysis of the canine T-cell receptor gamma locus (TCRγ) rearrangement. The dog presented with symmetrical generalized alopecia. Testicular enlargement was noted which on castration was determined to be caused by bilateral interstitial cell tumours, Sertoli cell tumours and a unilateral seminoma. During the four months after castration the alopecia became more severe and widespread. Histopathology of the skin showed moderate, multifocal, mural folliculitis, peribulbar mucinosis and lymphocytic bulbitis, and targeting of anagen hair follicles. Immunophenotyping of the infiltrate showed a population of well-differentiated, small CD3-positive T lymphocytes, some expressing CD4 and others CD8. Molecular analysis revealed a polyclonal lymphocytic infiltrate, substantiating the diagnosis of alopecia areata rather than lymphoma. Treatment with ciclosporin (4.6 mg/kg) and ketoconazole (4.6 mg/kg) resulted in complete hair regrowth. Ciclosporin treatment, in combination with ketoconazole, can be effective for treatment of alopecia universalis in the dog. Alopecia universalis may present with clinically noninflammatory, symmetrical, generalized alopecia, mimicking an endocrine alopecia, and skin biopsies are needed to confirm the diagnosis. © 2016 ESVD and ACVD.

Pathophysiology of ocular surface squamous neoplasia

PubMed Central

Gichuhi, Stephen; Ohnuma, Shin-ichi; Sagoo, Mandeep S.; Burton, Matthew J.

2014-01-01

The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva. PMID:25447808

Medical Devices; Hematology and Pathology Devices; Classification of a Cervical Intraepithelial Neoplasia Test System. Final order.

PubMed

2018-01-03

The Food and Drug Administration (FDA or we) is classifying the cervical intraepithelial neoplasia (CIN) test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the CIN test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Addison disease and normocalcemic primary hyperparathyroidism in a dog with multiple endocrine neoplasia.

PubMed

Arias, Elber Alberto Soler; Castillo, Victor Alejandro; Trigo, Roberto Hector

2017-01-01

A 12-year old dog with a 9-year history of primary adrenal insufficiency was referred to the service for hyporexia, muscle weakness, polyuria and polydipsia. Ultrasound examination showed an unresectable mass in the left adrenal gland, with local vascular invasion, which prompted the euthanasia of the animal. Additionally, necropsy revealed a nodular lesion in the right adrenal gland and enlargement of one of the four parathyroid glands. Parathyroid hormone levels were elevated, but ionized and total calcium levels were normal. Histopathology supported the diagnosis of parathyroid chief cell adenoma and bilateral pheochromocytoma. Immunohistochemical staining was positive for synaptophysin, and negative for Melan-A and calretinin, which confirmed the diagnosis of pheochromocytoma. This case highlights an unusual presentation of multiple endocrine neoplasias within the context of primary adrenal insufficiency and normocalcemic primary hyperparathyroidism.

Addison disease and normocalcemic primary hyperparathyroidism in a dog with multiple endocrine neoplasia

PubMed Central

Arias, Elber Alberto Soler; Castillo, Victor Alejandro; Trigo, Roberto Hector

2017-01-01

A 12-year old dog with a 9-year history of primary adrenal insufficiency was referred to the service for hyporexia, muscle weakness, polyuria and polydipsia. Ultrasound examination showed an unresectable mass in the left adrenal gland, with local vascular invasion, which prompted the euthanasia of the animal. Additionally, necropsy revealed a nodular lesion in the right adrenal gland and enlargement of one of the four parathyroid glands. Parathyroid hormone levels were elevated, but ionized and total calcium levels were normal. Histopathology supported the diagnosis of parathyroid chief cell adenoma and bilateral pheochromocytoma. Immunohistochemical staining was positive for synaptophysin, and negative for Melan-A and calretinin, which confirmed the diagnosis of pheochromocytoma. This case highlights an unusual presentation of multiple endocrine neoplasias within the context of primary adrenal insufficiency and normocalcemic primary hyperparathyroidism. PMID:29296592

Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia.

PubMed

Tirone, Nelson R; Peghini, Bethanea C; Barcelos, Ana Cristina M; Murta, Eddie F C; Michelin, Marcia A

2009-12-01

The present study evaluated mRNA expression of interferon-alpha (IFN-alpha), IFN-alpha receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated gene encoding the enzyme 2',5'-oligoadenylate synthetase (2'5'OAS) in biopsies on patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and III). Uterine cervix biopsies were collected from women with CIN I, II and III (n = 28) and controls without CIN lesions or human papilloma virus (HPV) infection (n = 17). The presence of high and low-risk HPV DNA was determined using hybrid capture. The mRNA levels of IFNAR-1, IFNAR-2, IFN-alpha and 2'5'OAS were determined by RT-PCR with specific primers. The control group exhibited a greater frequency of IFNAR-1 expression (10/17; 58.3%) than the CIN samples (4/28; 14.2%) (P = 0.0018), while, the expression of IFNAR-2 was also greater in the control samples (11/17; 64.7%) than in the patients with lesions (2/28; 7.1%) (P = 0.0018). Importantly, simultaneous expression of both receptors was observed only in the control group (8/17; 47.0%) (P = 0.0001). Among the CIN samples, there was one case of low expression of mRNA of IFNAR-1 and IFNAR-2. IFN-alpha was present in 14.2% (4/28) of the CIN samples but was not expressed in the control group. mRNA 2'5'OAS were expressed in 28.5% (8/28) of the CIN samples and 11.7% (2/17) of the control samples (not statistically significant). Fifty percent (14/28) of the CIN samples were positive for HPV DNA. Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group. There was no significant difference in mRNA expression of IFN-alpha and 2'5'OAS between the control and CIN groups. Then we concluded that the samples obtained from patients with CIN present low levels of the IFN-alpha receptor mRNA.

THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS

EPA Science Inventory

THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS.

Abstract:

The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...

Evaluation of candidate methylation markers to detect cervical neoplasia.

PubMed

Shivapurkar, Narayan; Sherman, Mark E; Stastny, Victor; Echebiri, Chinyere; Rader, Janet S; Nayar, Ritu; Bonfiglio, Thomas A; Gazdar, Adi F; Wang, Sophia S

2007-12-01

Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer. In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions.

High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference?

PubMed

Crawshaw, Benjamin P; Russ, Andrew J; Stein, Sharon L; Reynolds, Harry L; Marderstein, Eric L; Delaney, Conor P; Champagne, Bradley J

2015-01-01

High-resolution anoscopy has been shown to improve identification of anal intraepithelial neoplasia but a reduction in progression to anal squamous-cell cancer has not been substantiated when serial high-resolution anoscopy is compared with traditional expectant management. The aim of this study was to compare high-resolution anoscopy versus expectant management for the surveillance of anal intraepithelial neoplasia and the prevention of anal cancer. This is a retrospective review of all patients who presented with anal squamous dysplasia, positive anal Pap smears, or anal squamous-cell cancer from 2007 to 2013. This study was performed in the colorectal department of a university-affiliated, tertiary care hospital. Included patients had biopsy-proven anal intraepithelial neoplasia from 2007 to 2013. Patients were treated with high-resolution anoscopy with ablation or standard anoscopy with ablation. Both groups were treated with imiquimod and followed every 6 months indefinitely. The incidence of anal squamous-cell cancer in each group was the primary end point. From 2007 to 2013, 424 patients with anal squamous dysplasia were seen in the clinic (high-resolution anoscopy, 220; expectant management, 204). Three patients (high-resolution anoscopy, 1; expectant management, 2) progressed to anal squamous-cell cancer; 2 were noncompliant with follow-up and with HIV treatment, and the third was allergic to imiquimod and refused to take topical 5-fluorouracil. The 5-year progression rate was 6.0% (95% CI, 1.5-24.6) for expectant management and 4.5% (95% CI, 0.7-30.8) for high-resolution anoscopy (p = 0.37). This was a retrospective review. There is potential for selection and referral bias. Because of the rarity of the outcome, the study may be underpowered. Patients with squamous-cell dysplasia followed with expectant management or high-resolution anoscopy rarely develop squamous-cell cancer if they are compliant with the protocol. The cost, morbidity, and value of high

Disease course and management strategy of pouch neoplasia in patients with underlying inflammatory bowel diseases.

PubMed

Wu, Xian-Rui; Remzi, Feza H; Liu, Xiu-Li; Lian, Lei; Stocchi, Luca; Ashburn, Jean; Shen, Bo

2014-11-01

To evaluate the disease course and management strategy for pouch neoplasia. Patients undergoing ileal pouch surgery for underlying ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia, or adenocarcinoma in the pouch were identified. All eligible 44 patients were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%) had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years. Family history of colorectal cancer was shown to be a risk factor associated with persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high-grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4, 33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3 patients (25.0%) after the initial management, during a median time interval of 5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%) died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14, 32.6%), and those with dysplasia (29, 67.4%) showed that patients with adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis or pouch construction to the detection of pouch neoplasia (P = 0.007 and P = 0.0013). The risk for progression of pouch dysplasia can be stratified. The presence of family history of colorectal cancer seemed to increase the risk for persistence or progression for patients with pouch LGD. The prognosis for pouch adenocarcinoma was poor.

Prospective Evaluation of Multimodal Optical Imaging with Automated Image Analysis to Detect Oral Neoplasia In Vivo.

PubMed

Quang, Timothy; Tran, Emily Q; Schwarz, Richard A; Williams, Michelle D; Vigneswaran, Nadarajah; Gillenwater, Ann M; Richards-Kortum, Rebecca

2017-10-01

The 5-year survival rate for patients with oral cancer remains low, in part because diagnosis often occurs at a late stage. Early and accurate identification of oral high-grade dysplasia and cancer can help improve patient outcomes. Multimodal optical imaging is an adjunctive diagnostic technique in which autofluorescence imaging is used to identify high-risk regions within the oral cavity, followed by high-resolution microendoscopy to confirm or rule out the presence of neoplasia. Multimodal optical images were obtained from 206 sites in 100 patients. Histologic diagnosis, either from a punch biopsy or an excised surgical specimen, was used as the gold standard for all sites. Histopathologic diagnoses of moderate dysplasia or worse were considered neoplastic. Images from 92 sites in the first 30 patients were used as a training set to develop automated image analysis methods for identification of neoplasia. Diagnostic performance was evaluated prospectively using images from 114 sites in the remaining 70 patients as a test set. In the training set, multimodal optical imaging with automated image analysis correctly classified 95% of nonneoplastic sites and 94% of neoplastic sites. Among the 56 sites in the test set that were biopsied, multimodal optical imaging correctly classified 100% of nonneoplastic sites and 85% of neoplastic sites. Among the 58 sites in the test set that corresponded to a surgical specimen, multimodal imaging correctly classified 100% of nonneoplastic sites and 61% of neoplastic sites. These findings support the potential of multimodal optical imaging to aid in the early detection of oral cancer. Cancer Prev Res; 10(10); 563-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Vulvar Intraepithelial Neoplasia 3 in Women Less Than 35 Years

PubMed Central

Kesterson, Joshua P.; Lele, Shashikant

2016-01-01

Objective To examine the outcome of women diagnosed with vulvar intraepithelial neoplasia (VIN) 3 at less than 35 years. Materials and Methods All cases of VIN 3 treated in women less than 35 years treated at Roswell Park Cancer Institute between January 1973 and January 2008 were reviewed. Medical records were reviewed for year of diagnosis, treatment modality, recurrence and/or progression, associated medical conditions, history of genital condyloma, smoking status, history of cervical pathology, and treatment. Results Thirty-one women were identified. The mean age at diagnosis was 29 years. Smoking status was available in 28 patients, of which 82% (23/28) were current or former smokers. Eighty-one percent (25/31) of the women had cervical disease. Fifty-two percent (16/31) had a history of genital condyloma. Ten of the 31 women (32%) were diagnosed with persistence or recurrence of VIN 3. Three women (9.7%) progressed to invasive carcinoma. Conclusions Women diagnosed with VIN 3 at less than 35 years are at risk for persistence and/or recurrence of their disease as well as progression to carcinoma, warranting frequent and prolonged follow-up with liberal utilization of directed biopsies of suspicious lesions. PMID:27942201

Vulvar Intraepithelial Neoplasia 3 in Women Less Than 35 Years.

PubMed

Kesterson, Joshua P; Lele, Shashikant

2009-10-01

To examine the outcome of women diagnosed with vulvar intraepithelial neoplasia (VIN) 3 at less than 35 years. All cases of VIN 3 treated in women less than 35 years treated at Roswell Park Cancer Institute between January 1973 and January 2008 were reviewed. Medical records were reviewed for year of diagnosis, treatment modality, recurrence and/or progression, associated medical conditions, history of genital condyloma, smoking status, history of cervical pathology, and treatment. Thirty-one women were identified. The mean age at diagnosis was 29 years. Smoking status was available in 28 patients, of which 82% (23/28) were current or former smokers. Eighty-one percent (25/31) of the women had cervical disease. Fifty-two percent (16/31) had a history of genital condyloma. Ten of the 31 women (32%) were diagnosed with persistence or recurrence of VIN 3. Three women (9.7%) progressed to invasive carcinoma. Women diagnosed with VIN 3 at less than 35 years are at risk for persistence and/or recurrence of their disease as well as progression to carcinoma, warranting frequent and prolonged follow-up with liberal utilization of directed biopsies of suspicious lesions.

Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia.

PubMed

Li, J N; Mahmoud, M A; Han, W F; Ripple, M; Pizer, E S

2000-11-25

Endogenous fatty acid synthesis has been observed in certain rapidly proliferating normal and neoplastic tissues. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of lipogenic genes including fatty acid synthase (FAS), the major biosynthetic enzyme for fatty acid synthesis. We have previously shown that SREBP-1, FAS, and Ki-67, a proliferation marker, colocalized in the crypts of the fetal gastrointestinal tract epithelium. This study sought to determine whether SREBP-1 participates in the regulation of proliferation-associated fatty acid synthesis in colorectal neoplasia. An immunohistochemical analysis of SREBP-1, FAS, and Ki-67 expression in 25 primary human colorectal carcinoma specimens showed colocalization in 22 of these. To elucidate a functional linkage between SREBP-1 activation and proliferation-associated FA synthesis, SREBP-1 and FAS content were assayed during the adaptive response of cultured HCT116 colon carcinoma cells to pharmacological inhibition of FA synthesis. Cerulenin and TOFA each inhibited the endogenous synthesis of fatty acids in a dose-dependent manner and each induced increases in both precursor and mature forms of SREBP-1. Subsequently, both the transcriptional activity of the FAS promoter in a luciferase reporter gene construct and the FAS expression increased. These results demonstrate that tumor cells recognize and respond to a deficiency in endogenous fatty acid synthesis by upregulating both SREBP-1 and FAS expression and support the model that SREBP-1 participates in the transcriptional regulation of lipogenic genes in colorectal neoplasia. Copyright 2000 Academic Press.

Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

PubMed

Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

2016-07-03

Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

The impact of written information and counseling (WOMAN-PRO II Program) on symptom outcomes in women with vulvar neoplasia: A multicenter randomized controlled phase II study.

PubMed

Raphaelis, Silvia; Mayer, Hanna; Ott, Stefan; Mueller, Michael D; Steiner, Enikö; Joura, Elmar; Senn, Beate

2017-07-01

To determine whether written information and/or counseling based on the WOMAN-PRO II Program decreases symptom prevalence in women with vulvar neoplasia by a clinically relevant degree, and to explore the differences between the 2 interventions in symptom prevalence, symptom distress prevalence, and symptom experience. A multicenter randomized controlled parallel-group phase II trial with 2 interventions provided to patients after the initial diagnosis was performed in Austria and Switzerland. Women randomized to written information received a predefined set of leaflets concerning wound care and available healthcare services. Women allocated to counseling were additionally provided with 5 consultations by an Advanced Practice Nurse (APN) between the initial diagnosis and 6months post-surgery that focused on symptom management, utilization of healthcare services, and health-related decision-making. Symptom outcomes were simultaneously measured 5 times to the counseling time points. A total of 49 women with vulvar neoplasia participated in the study. Symptom prevalence decreased in women with counseling by a clinically relevant degree, but not in women with written information. Sporadically, significant differences between the 2 interventions could be observed in individual items, but not in the total scales or subscales of the symptom outcomes. The results indicate that counseling may reduce symptom prevalence in women with vulvar neoplasia by a clinically relevant extent. The observed group differences between the 2 interventions slightly favor counseling over written information. The results justify testing the benefit of counseling thoroughly in a comparative phase III trial. Copyright © 2017 Elsevier Inc. All rights reserved.

Nutritional agents with anti-inflammatory properties in chemoprevention of colorectal neoplasia.

PubMed

Hull, Mark A

2013-01-01

The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer (CRC). Several naturally occurring substances with anti-inflammatory properties, used in a purified 'nutraceutical' form, including omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and polyphenols such as curcumin and resveratrol, have been demonstrated to have anti-CRC activity in preclinical models. As expected, these agents have an excellent safety and tolerability profile in Phase II clinical trials. Phase III randomized clinical trials of these naturally occurring substances are now beginning to be reported. The omega-3 polyunsaturated fatty acid EPA, in the free fatty acid (FFA) form, has been demonstrated to reduce adenomatous polyp number and size in patients with familial adenomatous polyposis (FAP), a finding which has prompted evaluation of this formulation of EPA for prevention of 'sporadic' colorectal neoplasia. Anti-inflammatory 'nutraceuticals' require further clinical evaluation in polyp prevention trials as they exhibit many of the characteristics of the ideal cancer chemoprevention agent, including safety, tolerability and patient acceptability.

Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

PubMed Central

Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

2017-01-01

Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. PMID:28272465

[Local treatment of cervical intraepithelial neoplasia with a 5 percent fluorouracil ointment].

PubMed

Barten, G

1987-01-01

The results of treatment of histologically proven cervical intraepithelial neoplasia (CIN) in 10 women are described. Two of them had CIN I and 8 CIN III. All patients had a application of 5 g 5 per cent 5-fluorouracil cream in a cervical cup daily over a period of 12 hours for one week. All 10 patients have been examined colposcopically, cytological and by biopsy following therapy. In 8 women cone biopsie were done 6-12 months afterwards for having a final diagnosis 2 patients having CIN I pretherapeutically were follow up for 16 months with cytology, colposcopy and punch biopsy. In 6 cases we found better findings (Twice complete healing, twice only CIN I and twice CIN II as residues). In 4 cases severe dysplasia and carcinoma in situ could be found in endocervix. Based on these results were recommended more (not only one) treatment cycles for local efficient chemotherapy using 5 per cent 5-fluorouracil cream.

The incidence of human papillomavirus infection following treatment for cervical neoplasia: A systematic review

PubMed Central

Rositch, Anne F.; Soeters, Heidi M.; Offutt-Powell, Tabatha N.; Wheeler, Bradford S.; Taylor, Sylvia M.; Smith, Jennifer S.

2015-01-01

Objective To systematically review the published literature in order to estimate the incidence and describe the variability of human papillomavirus (HPV) infection in women following treatment for cervical neoplasia. Methods Several scientific literature databases (e.g. PubMed, ISI Web of Science) were searched through January 31, 2012. Eligible articles provided data on (i) baseline HPV infection status within 6 months prior to or at time of treatment (pre-treatment); and (ii) HPV test results for women's first visit after treatment occurring within 36 months (post-treatment). We abstracted and summarized the post-treatment incidence of newly detected HPV genotypes that were not present at pre-treatment, overall and stratified by study and other population characteristics. Results A total of 25 studies were included, reporting post-treatment HPV incidence in nearly 2000 women. Mean patient age ranged from 31 to 43 years (median 36). Most studies used cervical exfoliated cell specimens to test for HPV DNA (n = 20; 80%), using polymerase chain reaction (n = 21; 84%). Cervical neoplasia treatment included loop electrical excision procedure (n = 11; 44%); laser conization (n = 2; 8%); laser ablation, surgical conization, cryotherapy, alpha-interferon (n = 1; 4% each); or multiple treatment regimens (n = 8; 32%). Follow-up times post-treatment ranged from 1.5 to 36 months (median 6). More than half of studies (n = 17; 68%) estimated the incidence of any HPV type following treatment, while 7 (28%) focused specifically on high-risk (HR) HPV. HPV incidence after treatment varied widely, ranging from 0 to 47% (interquartile range: 0%-15%) in up to 3 years of follow-up after treatment. Lower HPV incidence was observed among studies that included relatively younger women, used laser conization, focused on HR-HPV rather than overall HPV infection, and had a lower proportion of recurrent cervical disease. Conclusions These modest summary incidence estimates from the published

Measurement of plasma cell-free DNA concentrations in dogs with sepsis, trauma, and neoplasia.

PubMed

Letendre, Jo-Annie; Goggs, Robert

2017-05-01

To determine if cell-free DNA (cfDNA) was identifiable in canine plasma, to evaluate 3 techniques for the measurement of plasma cfDNA concentrations in dogs presented to an emergency service, and to compare the plasma cfDNA concentrations of healthy dogs to those with sepsis, trauma, and neoplasia. Retrospective study of banked canine plasma samples collected between May 2014 and December 2014. Dogs presented to the emergency service of a university veterinary teaching hospital. Plasma cfDNA was measured on residual plasma samples obtained from 15 dogs with sepsis, 15 dogs with moderate-severe trauma, 15 dogs diagnosed with a sarcoma. Plasma cfDNA was also measured in 15 healthy dogs. None. Assay linearity, repeatability, and reproducibility were evaluated. Quantification of cfDNA was performed in duplicate on diluted citrated plasma and following DNA purification using 2 fluorescence assays (SYBR-Gold; Quant-iT) and by ultraviolet absorbance spectroscopy. Fluorescence intensities (FIs) were converted to cfDNA concentrations using standard curves. Median FI values and cfDNA concentrations were compared to healthy controls using the Kruskal-Wallis test, with adjustment for multiple comparisons. Alpha was set at 0.05. Both assays had excellent linearity, and acceptable repeatability and reproducibility. Compared to controls, plasma cfDNA concentrations were significantly increased in dogs with sepsis or moderate-severe trauma with both assays (P ≤ 0.003). Dogs with neoplasia had significantly increased cfDNA concentrations with the Quant-iT assay only (P = 0.003). When measurements were performed on purified DNA, only dogs with moderate-severe trauma had significantly increased cfDNA concentrations (P < 0.001; SYBR-Gold assay). cfDNA can be readily identified in canine plasma using 2 fluorescence assays. DNA extraction offers no advantage over direct measurement. Compared to healthy controls, dogs with sepsis or moderate-severe trauma have significantly increased

Self-administered topical imiquimod treatment of vulvar intraepithelial neoplasia. A report of four cases.

PubMed

Davis, G; Wentworth, J; Richard, J

2000-08-01

Vulvar intraepithelial neoplasia (VIN) generally can be classified into viral and nonviral etiologies. The histopathologic diagnosis is often separable into basaloid and warty types. A large percentage of VIN lesions have been shown to harbor human papillomavirus (HPV), principally type 16. Imiquimod, an immune response modifier, has been shown to be safe and effective for the treatment of external and perianal genital warts caused by HPV. Four cases occurred of clinical and histopathologically diagnosed viral VIN 3. An imiquimod treatment protocol, previously used in a study of this drug for the treatment of external genital warts, was followed. Imiquimod 5% cream was patient applied three times per week until all lesions cleared, for a maximum of 16 weeks. Imiquimod may be an effective treatment modality for viral VIN 3 in the future.

Smoking, sun exposure, number of nevi and previous neoplasias are risk factors for melanoma in older patients (60 years and over).

PubMed

Nagore, E; Hueso, L; Botella-Estrada, R; Alfaro-Rubio, A; Serna, I; Guallar, Jp; González, I; Ribes, I; Guillen, C

2010-01-01

Malignant melanoma risk factors have been studied in different geographical area populations. However, no study has focused on risk factors which are more frequently associated to the over 60's age group. A case-control study was performed that included 160 patients age > or = 60 years diagnosed of cutaneous melanoma and 318 controls matched for age and sex. Both groups were assessed, by personal interview and physical examination, for different phenotype characteristics (hair and eye color, phototype), the presence of other cutaneous lesions (solar lentigines, actinic keratoses and nevi), degree and type of solar exposure and personal and family past history of cutaneous or non-cutaneous cancer. Differences were evaluated by contingency tables and univariate and multivariate logistic regression. Of 17 factors, those risk factors with a strong effect on the development of melanoma in the elderly were: fair eyes, severe sunburns, years of occupational sun exposure, smoking, > 50 melanocytic nevi and personal history of NMSC and other non-cutaneous neoplasias. Tobacco smoking is an independent risk factor for cutaneous melanoma in the elderly. Intense (both acute and chronic) sun exposure and constitutional features, such as tumor susceptibility (NMSC, non-cutaneous neoplasias, and multiple nevi) are also associated with melanoma risk. All these factors should help to better design educational campaigns in older people.

Altered Gene Expression Patterns During the Initiation and Promotion Stages of Neonatally Diethylstilbestrol-Induced Hyperplasia/Dysplasia/Neoplasia in the Hamster Uterus

PubMed Central

Hendry, William J.; Hariri, Hussam Y.; Alwis, Imala D.; Gunewardena, Sumedha S.; Hendry, Isabel R.

2014-01-01

Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: 1) immunoblot analyses and 2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and 3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: 1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and 2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Particularly interesting changes included members in the functional categories of nuclear receptors (progesterone receptor), cell-cell interactions (E-cadherin, connexins), cytokine action (IRF-1, Stat5A), growth factor action (IRS-1), extracellular matrix component (tenascin-C), transcription factors (Nrf2, Sp1), and multi-functional nuclear protein (SAFB1). PMID:25242112

[Prevalence of HPV-induced lesions in the anal canal among women with cervical intraepithelial neoplasia 2 and 3: cross-sectional study].

PubMed

Heráclio, Sandra de Andrade; de Araujo, Thaís Antunes; Souza, Alex Sandro Rolland; Cahen, Kristiane; Lima Junior, Sergio Ferreira; de Souza, Paulo Roberto Eleutério; Amorim, Melania Maria Ramos

2015-10-01

To determine the prevalence of HPV-induced lesions in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade 2/3. A cross-sectional study was carried out from December 2008 to June 2009, in Pernambuco, northeastern Brazil. Only women with grade 2/3 CIN were included, and those who could not undergo anoscopy during their first visit were excluded. A cyttobrush was used for sample collection in order to identify HPV DNA through PCR and anal cytology. An anal biopsy was obtained in cases of abnormal anal cytology or major alterations in high resolution anoscopy (HRA). Thirty-two percent (n=37/115) of HRA were normal and 63.5% (n=73/115) showed acetowhite epithelium. Twenty-two percent (n=26/115) of anal cytologies were abnormal. Among the latter, 12.2% (n=14/26) were low-grade anal intraepithelial lesions and 3.4% (n=4/26) were high-grade anal intraepithelial lesions. Twenty-two anal biopsies were performed, 13.7% of which (n=3/22) were grade 2 anal intraepithelial neoplasia (AIN2) and 9% (n=2/22) were grade 3 AIN. Th HPV DNA was identified in 72.1% of cases (n=83/115). Women with CIN grade 2/3 showed a high prevalence of anal HPV infection and HPV-induced lesions.

Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

PubMed

Sun, Xun; Arnous, Maher Mohamad Rajab; Lan, Xiaoli

2017-04-01

F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

Changes in Adult BMI and Waist Circumference Are Associated with Increased Risk of Advanced Colorectal Neoplasia.

PubMed

Gathirua-Mwangi, Wambui G; Monahan, Patrick; Song, Yiqing; Zollinger, Terrell W; Champion, Victoria L; Stump, Timothy E; Imperiale, Thomas F

2017-11-01

Waist circumference (WC) is a stronger predictor of colon cancer (CRC) risk than body mass index (BMI). However, how well change in either WC or BMI predicts risk of advanced colorectal neoplasia (AN) is unclear. To determine the relationship between change in BMI and WC from early adulthood to later age and the risk of AN and which change measure is a stronger predictor. In 4500 adults, ages 50-80, with no previous neoplasia and undergoing screening colonoscopy, BMI and WC at age 21 and at time of screening were reported. Changes in BMI and WC were defined using universal risk cutoffs. Known CRC risk factors were controlled in the logistic models. Overall, model statistics showed WC change (omnibus test χ 2  = 10.15, 2 DF, p value = 0.006) was a statistically stronger predictor of AN than BMI change (omnibus test χ 2  = 5.66, 5 DF, p value = 0.34). Independent of BMI change, participants who increased WC (OR 1.44; 95% CI 1.05-1.96) or maintained a high-risk WC (OR 2.50; 95% CI 1.38-4.53) at age 21 and at screening had an increased risk of AN compared to those with a low-risk WC. Study participants who were obese at age 21 and at screening had an increased risk of AN (OR 1.87; 95% CI 1.08-3.23) compared to those who maintained a healthy BMI. Maintaining an overweight BMI or increasing BMI was not associated with AN. Maintaining an unhealthy BMI and WC throughout adult life may increase risk of AN. WC change may be a better predictor of AN than BMI change.

Human papillomavirus DNA detection in menstrual blood from patients with cervical intraepithelial neoplasia and condyloma acuminatum.

PubMed

Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-03-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases.

Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

PubMed

Galor, Anat; Garg, Nisha; Nanji, Afshan; Joag, Madhura; Nuovo, Gerard; Palioura, Sotiria; Wang, Gaofeng; Karp, Carol L

2015-11-01

To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. Retrospective case series. Twenty-seven patients with OSSN. Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. Clinical characteristics of OSSN by HPV status. Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

Age-related changes in pre- and post-conization HPV genotype distribution among women with high-grade cervical intraepithelial neoplasia.

PubMed

Giannella, Luca; Fodero, Cristina; Boselli, Fausto; Rubino, Teresa; Mfuta, Kabala; Prandi, Sonia

2017-04-01

To assess the effect of age on pre- and post-conization HPV genotype distribution. The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (<30, 30-39, 40-49, and ≥50 years) and age-related changes in the HPV genotypes present were evaluated. There were 162 patients included. The lowest occurrence of pre-conization high-risk and probable high-risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post-conization high-risk and probable high-risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre- and post-conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post-treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030). The presence of high-risk and probable high-risk HPV genotypes was lowest among older patients before conization and was highest among these patients post-conization; post-treatment HPV clearance decreased with age and increasing age could be a risk factor for post-conization recurrence. © 2017 International Federation of Gynecology and Obstetrics.

Number of fragments, margin status and thermal artifacts of conized specimens from LLETZ surgery to treat cervical intraepithelial neoplasia.

PubMed

Bittencourt, Dulcimary Dias; Zanine, Rita Maira; Sebastião, Ana Martins; Taha, Nabiha Saadi; Speck, Neila Góis; Ribalta, Julisa Chamorro Lascasas

2012-01-01

Large loop excision of the transformation zone (LLETZ) is a nontraumatic cut and coagulation method with several advantages, but it induces thermal artifacts in the cut region. The aim here was to assess the correlations of age, number of fragments, lesion grade and degree of thermal artifacts with margin quality in conized specimens from LLETZ for cervical intraepithelial neoplasia (CIN). Cross-sectional study at Universidade Federal de São Paulo (Unifesp). The records and histopathology findings of 118 women who underwent LLETZ between 1999 and 2007 were reviewed. Age, number of fragments, lesion grade, degree of thermal artifacts and margin quality were assessed. The patients' mean age was 27.14 years; 63.6% had been diagnosed with CIN II and 36.4% with CIN III. The lesion was removed as a single fragment in 79.6% of the cases. The margins were free from intraepithelial neoplasia in 85.6% and compromised in the endocervical margin in 6.8%. Fragment damage due to artifacts occurred in 2.5%. Severe artifacts occurred in 22.8%. Women aged 30 years or over presented more cases of CIN III (P < 0.0004). Neoplastic compromising of surgical margins and severe artifacts occurred more often in cases in which two or more fragments were removed, and in patients aged 30 years or over. CIN III in women aged 30 or over, when removed in two or more fragments during LLETZ, presented a greater number of compromised margins and greater severity of thermal artifacts.

MicroRNAs for Detection of Pancreatic Neoplasia

PubMed Central

Vila-Navarro, Elena; Vila-Casadesús, Maria; Moreira, Leticia; Duran-Sanchon, Saray; Sinha, Rupal; Ginés, Àngels; Fernández-Esparrach, Glòria; Miquel, Rosa; Cuatrecasas, Miriam; Castells, Antoni; Lozano, Juan José; Gironella, Meritxell

2017-01-01

Objective: The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia. Objective: Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates. Methods: Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1—52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2—95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C). Results: In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively. Conclusions: miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer. PMID:27232245

A patient-reported outcome measure to identify occurrence and distress of post-surgery symptoms of WOMen with vulvAr Neoplasia (WOMAN-PRO) - a cross sectional study.

PubMed

Senn, Beate; Eicher, Manuela; Mueller, Michael D; Hornung, René; Fink, Daniel; Baessler, Kaven; Hampl, Monika; Denhaerynck, Kris; Spirig, Rebecca; Engberg, Sandra

2013-04-01

The aim of the study was to describe the (a) symptom experience of women with vulvar intraepithelial neoplasia and vulvar cancer (vulvar neoplasia) during the first week after hospital discharge, and (b) associations between age, type of disease, stage of disease, the extent of surgical treatment and symptom experience. This cross-sectional study was conducted in eight hospitals in Germany and Switzerland (Clinical Trial ID: NCT01300663). Symptom experience after surgical treatment in women with vulvar neoplasia was measured with our newly developed WOMAN-PRO instrument. Outpatients (n=65) rated 31 items. We used descriptive statistics and regression analysis. The average number of symptoms reported per patient was 20.2 (SD 5.77) with a range of 5 to 31 symptoms. The three most prevalent wound-related symptoms were 'swelling' (n=56), 'drainage' (n=54) and 'pain' (n=52). The three most prevalent difficulties in daily life were 'sitting' (n=63), 'wearing clothes' (n=56) and 'carrying out my daily activities' (n=51). 'Tiredness' (n=62), 'insecurity' (n=54) and 'feeling that my body has changed' (n=50) were the three most prevalent psychosocial symptoms/issues. The most distressing symptoms were 'sitting' (Mean 2.03, SD 0.88), 'open spot (e.g. opening of skin or suture)' (Mean 1.91, SD 0.93), and 'carrying out my daily activities' (Mean 1.86, SD 0.87), which were on average reported as 'quite a bit' distressing. Negative associations were found between psychosocial symptom experience and age. WOMAN-PRO data showed a high symptom prevalence and distress, call for a comprehensive symptom assessment, and may allow identification of relevant areas in symptom management. Copyright © 2013 Elsevier Inc. All rights reserved.

A survey on the prevalence of high-risk subtypes of human papilloma virus among women with cervical neoplasia in Isfahan University of Medical Science.

PubMed

Allameh, Tajossadat; Moghim, Sharareh; Asadi-Zeidabadi, Maryam

2011-12-01

Given the importance of epidemiological studies on the prevalence of human papilloma virus (HPV) and its subtypes to plan more effective strategies for cervical cancer prevention, the aim of this study was to determine the prevalence of HPV in women with cervical intraepithelial neoplasia and cancer in Isfahan. In this descriptive cross-sectional study, women referred to oncology clinic of Shahid Beheshti Hospital because of abnormal cytology of their cervices within the last year were studied. The 2001 Bethesda system was used for histologic classification. The distribution of different pathologies was as follows: squamous cell carcinoma (SCC) 34.7%, low-grade squamous intraepithelial lesions (LSIL) 30.5%, high-grade squamous intraepithelial lesions (HSIL) 22.8%, atypical squamous cell of undetermined significance (ASCUS) 8.4%, and adenocarcinoma (AC) 3.3%. There was no case of atypical glandular of undetermined significance or cases of adenocarcinoma associated with an early lesion. The presence of HPV infection and its subtypes including HPV 16, 18, 6 and 11 was assessed in different cytological categories of cervical neoplasia, by using polymerase chain reaction method. During this study, 130 patients were studied. Their median age was 52 years (range 29-73 years). HPV was detected in 118/130 patients (90.8%) with abnormal cervical cytology. The prevalence of positive HPV samples was 97.6, 80, 93.1, 92.3, and 66.6% in cases with SCC, AC, HSIL, LSIL, and ASCUS, respectively (P < 0.05 between SCC and ASCUS, HSIL and ASCUS, and LSIL and ASCUS). Out of 118 cases with positive HPV, 98 (83.1%) were positive for multiple HPV types 16, 18, and 11 or 6. The distribution of studied HPV subtypes among women with positive HPV was as follows: 49.1% for both types 16 and 18, 10.1% for type 16, 1.69% for type 18 and 22% for type 11 or 6. The prevalence of HPV type 16 was not significantly different in various cytological categories of cervical neoplasia (P > 0.05). The

Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

PubMed

Ma, Changqing; Gocke, Christopher D; Hruban, Ralph H; Belchis, Deborah A

2016-02-01

Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

The Jak2 Inhibitor, G6, Alleviates Jak2-V617F-Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow1

PubMed Central

Kirabo, Annet; Park, Sung O; Majumder, Anurima; Gali, Meghanath; Reinhard, Mary K; Wamsley, Heather L; Zhao, Zhizhuang Joe; Cogle, Christopher R; Bisht, Kirpal S; Keserü, György M; Sayeski, Peter P

2011-01-01

We recently developed a Janus kinase 2 (Jak2) small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F-mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F-mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F-mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6). In the liver, G6 eliminated Jak2-V617F-driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the splenomegaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho-signal transducer and activator of transcription 5 (STAT5). It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67%on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F-mediated myeloproliferative neoplasia. PMID:22131881

Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm.

PubMed

Herfs, Michael; Crum, Christopher P

2013-03-01

Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

PubMed Central

Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

2016-01-01

Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

PubMed Central

Nagle, R. B.; Brawer, M. K.; Kittelson, J.; Clark, V.

1991-01-01

Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. Images Figure 4 Figure 1 Figure 2 Figure 3 PMID:1987760

Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia.

PubMed

Peghini, Bethânea Crema; Abdalla, Douglas Reis; Barcelos, Ana Cristina Macedo; Teodoro, Lívia das Graças Vieito Lombardi; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi

2012-09-01

Several studies have suggested that patients with cervical intraepithelial and invasive neoplasia have reduced levels of Th1 cytokines, and increased levels of Th2 cytokines. Thus, the aim of this study was to delineate the immunological profile associated with lesion progression. Biopsies were obtained from 28 patients with low grade cervical intraepithelial lesions (LSILs), 53 patients with high grade cervical intraepithelial lesions (HSILs), 25 patients with invasive cancer (CA), and 20 healthy controls. Levels of IFN-γ, TNF-α, IL-2, IL-4, IL-10, IL-12, TGF-β1 and TGF-β2 were then assayed by RT-PCR and ELISA for each biopsy sample. For LSILs, higher levels of Th1 cytokines were detected, while HSILs were associated with a Th2 cytokine profile. In contrast, CA tissues were associated with the strongest expression of a Treg cytokine profile. In conclusion the most important contribution of these work is identification of the Treg cytokine profile in HPV progression lesions and in combination, these results suggested that tumor progression is dependent on suppression of cellular immunity. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

PubMed

Sideri, Mario; Jones, Ronald W; Wilkinson, Edward J; Preti, Mario; Heller, Debra S; Scurry, James; Haefner, Hope; Neill, Sallie

2005-11-01

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

Planarians as models of cadmium-induced neoplasia provide measurable benchmarks for mechanistic studies.

PubMed

Voura, Evelyn B; Montalvo, Melissa J; Dela Roca, Kevin T; Fisher, Julia M; Defamie, Virginie; Narala, Swami R; Khokha, Rama; Mulligan, Margaret E; Evans, Colleen A

2017-08-01

Bioassays of planarian neoplasia highlight the potential of these organisms as useful standards to assess whether environmental toxins such as cadmium promote tumorigenesis. These studies complement other investigations into the exceptional healing and regeneration of planarians - processes that are driven by a population of active stem cells, or neoblasts, which are likely transformed during planarian tumor growth. Our goal was to determine if planarian tumorigenesis assays are amenable to mechanistic studies of cadmium carcinogenesis. To that end we demonstrate, by examining both counts of cell populations by size, and instances of mitosis, that the activity of the stem cell population can be monitored. We also provide evidence that specific biomodulators can affect the potential of planarian neoplastic growth, in that an inhibitor of metalloproteinases effectively blocked the development of the lesions. From these results, we infer that neoblast activity does respond to cadmium-induced tumor growth, and that metalloproteinases are required for the progression of cancer in the planarian. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiating vulvar intraepithelial neoplasia from nonneoplastic epithelial disorders. The toluidine blue test.

PubMed

Joura, E A; Zeisler, H; Lösch, A; Sator, M O; Müllauer-Ertl, S

1998-08-01

To determine the effectiveness of the toluidine blue test in the differentiation of vulvar intraepithelial neoplasia (VIN) and nonneoplastic epithelial disorders (NNEDs). This retrospective clinical study included all women with VIN (n = 24) and NNED (n = 72) referred to a vulvar clinic at a university hospital during a two-year period. Vulvoscopy, staining of vulvar epithelium with 1% toluidine blue and punch biopsy were performed. Vulvar epithelium demonstrated toluidine blue staining in 100% of the patients with VIN 3, in 83% of women with VIN 1-2, in 50% of the women with squamous cell hyperplasia and in 10% of the women with lichen sclerosus. The differences in staining between the groups were statistically significant (P < .001). The sensitivity of toluidine blue staining for the detection of VIN was 92%; the negative predictive value 96% in teh investigated cohort. The specificity for strong staining was 88%. The toluidine blue test is an inexpensive and reliable method of separating VIN from hyperplastic NNED areas and choosing a biopsy site on the vulva.

The effects of 5% imiquimod cream on high-grade vulval intraepithelial neoplasia.

PubMed

Todd, Richard W; Etherington, Ian J; Luesley, David M

2002-04-01

The aim of this study was to investigate the effects of topical 5% Imiquimod (3M Pharmaceuticals, St. Paul, Minnessota) on high-grade vulval intraepithelial neoplasia (VIN). A prospective uncontrolled observational study was performed. Fifteen patients with histologically confirmed VIN 3 were asked to self-administer 5% Imiquimod cream to their vulval lesions up to three times weekly for 16 weeks. Review was conducted at 1, 2, 3, 4, 6, and 9 months postrecruitment. Lesions were photodocumented and at 4 months any areas demonstrating a clinical response were biopsied. Of 15 patients recruited, 4 demonstrated a clinical improvement in their disease, 3 of whom had negative biopsies posttreatment. Local side effects limited the frequency of application such that 7 patients applied the cream once weekly, 6 twice weekly, and 2 three times weekly. 5% Imiquimod cream appears to have an effect when used on high-grade VIN. The frequency of application was limited by local side effects which may have reduced the clinical responses seen. Measures to alleviate local side effects may allow more aggressive use of Imiquimod and lead to improved responses.

The Pros and Cons of Army Automation

DTIC Science & Technology

2007-11-13

The Pros and Cons of Army Automation 1 Running Head: THE PROS AND CONS OF ARMY AUTOMATION The Pros and Cons of Army Automation SGM...TITLE AND SUBTITLE The Pros and Cons of Army Automation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Prescribed by ANSI Std Z39-18 The Pros and Cons of Army Automation 2 Outline I. Introduction (MSG (P) Dostie) II. Manual skills (MSG (P

Treatment of bowenoid and basaloid vulvar intraepithelial neoplasia 2/3 with imiquimod 5% cream.

PubMed

Marchitelli, Claudia; Secco, Graciela; Perrotta, Myriam; Lugones, Leonor; Pesce, Romina; Testa, Roberto

2004-11-01

To evaluate the effectiveness and safety of imiquimod 5% for the treatment of bowenoid and basaloid vulvar intraepithelial neoplasia (VIN) and to evaluate recurrences following treatment. Eight patients <55 years old (range, 32-51; mean, 39.7), with bowenoid or basaloid VIN 2/3 diagnosed by biopsy were treated with imiquimod 5%. Women with other types of intraepithelial neoplasia of the lower genital tract, immunosuppressed women, pregnant women and women with other types of vulvar pathology were excluded. Two patients previously treated for VIN 3 (surgical resection, resection by loop electrosurgical excision procedure) had recurrences. Patients applied imiquimod cream 3 times a week until total clearance of the lesions or up to a maximum of 16 weeks. Responses were categorized as total when there was no colposcopic evidence of a lesion, partial when the lesion area diminished >50% and progressive when there was an increase in the lesion area. A biopsy was performed at the end of treatment. Follow-up was carried out monthly (10-30 months). Total clearance of lesions was observed in 6 patients after 10-16 weeks. Two patients had a partial response (1 with 75% and the other with 50% reduction of the lesions). Posttreatment histopathology showed the absence of precancerous lesions in 7 patients (87.5%). Biopsy was positive for VIN 3 (12.5%) only in the patient showing a clinical response of 50%. Of the 7 patients with biopsies negative for VIN, 2 (25%) were positive for viral infection; 1 gave a negative reading after 2 months after treatment, and the other 1 remained positive for human papillomavirus. The patient with persistent VIN received surgical treatment. The side effects were as follows: erythema in 8 patients (100%), erosions in 1 patient (12.5%) and edema in 1 patient (12.5%). No relapses occurred after treatment during 10-30 months of follow-up. In this initial series, imiquimod proved to be effective for the treatment of bowenoid and basaloid VIN 2/3 in a

Experimental and Computational Studies of Carbonyl Diazide (CON6) as a Precursor to Diazirinone (CON2)

NASA Astrophysics Data System (ADS)

Esselman, Brian J.; Amberger, Brent K.; Nolan, Alex M.; Woods, R. Claude; McMahon, R. J.

2011-10-01

Intrigued by the reported 2005 synthesis of diazirinone (1), we carried out further experimental and theoretical studies aimed at the detailed matrix-isolation and millimeter-wave spectroscopic characterizations of 1. Diazirinone (1) is a peculiar isoconjugate of two very stable molecules and may be of astrochemical interest. Unfortunately, the original reported methods of diazirinone (1) generation did not yield this species, rather its decomposition products. Inspired by a more recent gas phase pyrolysis of CON6 (2) to yield CON2 (1), we proposed a new method of generating CON6 (2) in solution as a precursor of diazirinone (1). This new synthesis may allow us to generate larger quantities of both CON6 and CON2 for investigation by millimeter-wave spectroscopy. We are able to safely generate carbonyl diazide (2) in sufficient yield from the reaction of triphosgene (3) and tetrabutylammonium azide in diethyl ether. This has allowed us to obtain both matrix-isolation and gas phase IR spectra of carbonyl diazide (2). After purification, it has a gas-phase lifetime that allows samples to be useable for up to several weeks. However, it is a shock-sensitive material that must be handled with care to prevent violent decomposition. In order to provide better mechanistic insight into the decomposition of carbonyl diazide (2) to diazirinone (1), we have engaged in a DFT and ab initio computational study. We have found a pathway between the two species via the triplet acylnitrene, CON4, and an oxaziridine CON2 species, but not at sufficiently low energies to allow for the trapping and detection of diazirinone (1). Preliminary millimeter-wave spectra have been obtained from several synthesized and purified samples of CON6 (2). However, the assignment of the spectra lines has been unexpectedly problematic. We have placed several CON6 (2) samples, confirmed by IR spectroscopy at the time of sample loading, into our instrument and obtained two different sets of rotational lines

Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum ▿

PubMed Central

Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-01-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases. PMID:20089764

A meta-analysis of confocal laser endomicroscopy for the detection of neoplasia in patients with Barrett's esophagus.

PubMed

Xiong, Yi-Quan; Ma, Shu-Juan; Zhou, Jun-Hua; Zhong, Xue-Shan; Chen, Qing

2016-06-01

Barrett's esophagus (BE) is considered the most important risk factor for development of esophageal adenocarcinoma. Confocal laser endomicroscopy (CLE) is a recently developed technique used to diagnose neoplasia in BE. This meta-analysis was performed to assess the accuracy of CLE for diagnosis of neoplasia in BE. We searched EMBASE, PubMed, Cochrane Library, and Web of Science to identify relevant studies for all articles published up to June 27, 2015 in English. The quality of included studies was assessed using QUADAS-2. Per-patient and per-lesion pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals (CIs) were calculated. In total, 14 studies were included in the final analysis, covering 789 patients with 4047 lesions. Seven studies were included in the per-patient analysis. Pooled sensitivity and specificity were 89% (95% CI: 0.82-0.94) and 83% (95% CI: 0.78-0.86), respectively. Ten studies were included in the per-lesion analysis. Compared with the PP analysis, the corresponding pooled sensitivity declined to 77% (95% CI: 0.73-0.81) and specificity increased to 89% (95% CI: 0.87-0.90). Subgroup analysis showed that probe-based CLE (pCLE) was superior to endoscope-based CLE (eCLE) in pooled specificity [91.4% (95% CI: 89.7-92.9) vs 86.1% (95% CI: 84.3-87.8)] and AUC for the sROC (0.885 vs 0.762). Confocal laser endomicroscopy is a valid method to accurately differentiate neoplasms from non-neoplasms in BE. It can be applied to BE surveillance and early diagnosis of esophageal adenocarcinoma. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Incidence of macroscopically occult neoplasias in Barrett's esophagus: are random biopsies dispensable in the era of advanced endoscopic imaging?

PubMed

Pohl, Juergen; Pech, Oliver; May, Andrea; Manner, Hendrik; Fissler-Eckhoff, Annette; Ell, Christian

2010-11-01

The gold standard for endoscopic surveillance of Barrett's esophagus (BE) includes targeted biopsies (TBs) from abnormalities as well as stepwise four-quadrant biopsies (4QBs) for detection of invisible high-grade intraepithelial neoplasias (HGINs) or early carcinomas (ECs). In a large mixed BE population, we investigated the rate of HGINs/ECs that are macroscopically occult to enhanced visualization with high-resolution endoscopy plus acetic acid chromoendoscopy. From January 2007 to December 2009, 701 consecutive BE patients were enrolled in a prospective study at a tertiary referral center. Of these, 406 patients had a history of HGIN/EC (high-risk group) and 295 patients did not (low-risk group). In 701 patients, 459 TBs and 5,485 4QBs were obtained. Altogether, 92 patients with 132 lesions containing HGINs/ECs were detected. For the diagnosis of HGINs/ECs, patient-related sensitivity and specificity rates of endoscopic imaging with TBs were 96.7 and 66.5%, with a positive and negative predictive value of 30.4 and 99.3%, respectively. In the high-risk group, 4QBs identified three additional patients (3.3%) with macroscopically occult HGINs/ECs. In the low-risk group, no HGINs/ECs were identified with either biopsy approach. Advanced endoscopic imaging identifies the vast majority of BE patients with early neoplasias, and the additive effect of 4QB is minimal. Therefore, in low- and high-risk patients, limiting endoscopic surveillance to guided biopsies is justified in specialized high-volume centers with permanent quality control. However, we do not advocate abandoning 4QB outside this setting.

The radiological features, diagnosis and management of screen-detected lobular neoplasia of the breast: Findings from the Sloane Project.

PubMed

Maxwell, Anthony J; Clements, Karen; Dodwell, David J; Evans, Andrew J; Francis, Adele; Hussain, Monuwar; Morris, Julie; Pinder, Sarah E; Sawyer, Elinor J; Thomas, Jeremy; Thompson, Alastair

2016-06-01

To investigate the radiological features, diagnosis and management of screen-detected lobular neoplasia (LN) of the breast. 392 women with pure LN alone were identified within the prospective UK cohort study of screen-detected non-invasive breast neoplasia (the Sloane Project). Demography, radiological features and diagnostic and therapeutic procedures were analysed. Non-pleomorphic LN (369/392) was most frequently diagnosed among women aged 50-54 and in 53.5% was at the first screen. It occurred most commonly on the left (58.0%; p = 0.003), in the upper outer quadrant and confined to one site (single quadrant or retroareolar region). No bilateral cases were found. The predominant radiological feature was microcalcification (most commonly granular) which increased in frequency with increasing breast density. Casting microcalcification as a predominant feature had a significantly higher lesion size compared to granular and punctate patterns (p = 0.034). 326/369 (88.3%) women underwent surgery, including 17 who underwent >1 operation, six who had mastectomy and six who had axillary surgery. Two patients had radiotherapy and 15 had endocrine treatment. Pleomorphic lobular carcinoma in situ (23/392) presented as granular microcalcification in 12; four women had mastectomy and six had radiotherapy. Screen-detected LN occurs in relatively young women and is predominantly non-pleomorphic and unilateral. It is typically associated with granular or punctate microcalcification in the left upper outer quadrant. Management, including surgical resection, is highly variable and requires evidence-based guideline development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neoplasia and Neoplasm Associated Lesions in Laboratory Colonies of Zebrafish Emphasizing Key Influences of Diet and Aquaculture System Design

PubMed Central

Spitsbergen, Jan M.; Buhler, Donald R.; Peterson, Tracy S.

2014-01-01

During the past decade the zebrafish has emerged as a leading model for mechanistic cancer research due to its sophisticated genetic and genomic resources, its tractability for tissue targeting of transgene expression, its efficiency for forward genetic approaches to cancer model development, and its cost-effectiveness for enhancer and suppressor screens once a cancer model is established. However, in contrast to other laboratory animal species widely used as cancer models, much basic cancer biology information is lacking in zebrafish. As yet data are not published regarding dietary influences on neoplasm incidences in zebrafish. Little information is available regarding spontaneous tumor incidences or histologic types in wild-type (wt) lines of zebrafish. So far a comprehensive database documenting the full spectrum of neoplasia in various organ systems and tissues in not available for zebrafish as it is for other intensely studied laboratory animal species. This manuscript confirms that as in other species diet and husbandry can profoundly influence tumor incidences and histologic spectra in zebrafish. We show that in many laboratory colonies wt lines of zebrafish exhibit elevated neoplasm incidences and neoplasm associated lesions such as heptocyte megalocytosis. We present experimental evidence showing that certain diet and water management regimens can result in high incidences of neoplasia and neoplasm associated lesions. We document the wide array of benign and malignant neoplasms affecting nearly every organ, tissue and cell type in zebrafish, in some cases as a spontaneous aging change, and in other cases due to carcinogen treatment or genetic manipulation. PMID:23382343

Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia.

PubMed

Albuquerque, Andreia; Sheaff, Michael; Stirrup, Oliver; Cappello, Carmelina; Bowring, Julie; Cuming, Tamzin; de Masi, Anke; Rosenthal, Adam N; Nathan, Mayura

2018-04-05

Information on the performance of anal cytology in women who are high-risk for human papillomavirus-related lesions and the factors that might influence it are largely lacking. Evaluate the performance of anal cytology in women with lower anogenital tract neoplasia. retrospective study including all new referrals of women with a previous history of anogenital neoplasia, from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies. 636 anal cytology samples and 323 biopsies were obtained from 278 women. Overall sensitivity and specificity of 'any abnormality' on anal cytology to predict 'any abnormality' in histology was 47% (95% CI 41-54%) and 84% (95% CI 73-91%), respectively. For detecting high-grade squamous intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI 61-79%) and specificity was 73% (95% CI 66-79%). There was a poor concordance between cytological and histological grades (κ=0.147). Cytology had a higher sensitivity to predict HSIL/cancer in immunosuppressed vs. non-immunosuppressed patients (92% vs. 60%, P=0.002). The sensitivity for HSIL detection was higher when two or more quadrants were affected in comparison with only one (86% vs. 57%, P=0.006). A previous history of vulvar HSIL/cancer (OR 1.71, 1.08-2.73; P=0.023), immunosuppression (OR 1.88, 1.17-3.03; P=0.009) and concomitant genital HSIL/cancer (OR 2.51, 1.47-4.29; P=0.001) were risk factors for abnormal cytology. Patient characteristics can influence the performance of anal cytology in women. The sensitivity for detecting anal HSIL/cancer was higher in those immunosuppressed and with more extensive disease.

Fusobacterium’s link to colorectal neoplasia sequenced: A systematic review and future insights

PubMed Central

Hussan, Hisham; Clinton, Steven K; Roberts, Kristen; Bailey, Michael T

2017-01-01

AIM To critically evaluate previous scientific evidence on Fusobacterium’s role in colorectal neoplasia development. METHODS Two independent investigators systematically reviewed all original scientific articles published between January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355 articles were screened at the abstract level. Of these, only original scientific human, animal, and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer (CRC) were included in the analysis. Abstracts, review articles, studies investigating other colonic diseases, and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates, resolving disagreements between the two reviewers, and applying the above criteria. RESULTS Studies have consistently identified positive associations between Fusobacterium, especially Fusobacterium nucleatum (F. nucleatum), and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and CpG island methylator phenotype (CIMP)-high CRCs. There was evidence of temporality and a biological gradient, with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment; evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear; however, the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin (Gal-GalNAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors

Altered microRNA expression patterns during the initiation and promotion stages of neonatal diethylstilbestrol-induced dysplasia/neoplasia in the hamster (Mesocricetus auratus) uterus.

PubMed

Padmanabhan, Ramesh; Hendry, Isabel R; Knapp, Jennifer R; Shuai, Bin; Hendry, William J

2017-10-01

Treatment of Syrian hamsters on the day of birth with the prototypical endocrine disruptor and synthetic estrogen, diethylstilbestrol (DES), leads to 100% occurrence of uterine hyperplasia/dysplasia in adulthood, a large proportion of which progress to neoplasia (endometrial adenocarcinoma). Consistent with our prior gene expression analyses at the mRNA and protein levels, we now report (based on microarray, real-time polymerase chain reaction, and in situ hybridization analyses) that progression of the neonatal DES-induced dysplasia/neoplasia phenomenon in the hamster uterus also includes a spectrum of microRNA expression alterations (at both the whole-organ and cell-specific level) that differ during the initiation (upregulated miR-21, 200a, 200b, 200c, 29a, 29b, 429, 141; downregulated miR-181a) and promotion (downregulated miR-133a) stages of the phenomenon. The biological processes targeted by those differentially expressed miRNAs include pathways in cancer and adherens junction, plus regulation of the cell cycle, apoptosis, and miRNA functions, all of which are consistent with our model system phenotype. These findings underscore the need for continued efforts to identify and assess both the classical genetic and the more recently recognized epigenetic mechanisms that truly drive this and other endocrine disruption phenomena.

Lobular intraepithelial neoplasia arising within breast fibroadenoma

PubMed Central

2013-01-01

Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating

World Health Organization Guidelines: Use of cryotherapy for cervical intraepithelial neoplasia.

PubMed

Santesso, Nancy; Schünemann, Holger; Blumenthal, Paul; De Vuyst, Hugo; Gage, Julia; Garcia, Francisco; Jeronimo, Jose; Lu, Ricky; Luciani, Silvana; Quek, Swee C; Awad, Tahany; Broutet, Nathalie

2012-08-01

In 2008, cervical cancer was responsible for 275000 deaths, of which approximately 88% occurred in low- and middle-income countries. In 2009, the World Health Organization (WHO) committed to updating recommendations for use of cryotherapy for cervical intraepithelial neoplasia (CIN). We followed the WHO Handbook for Guidelines Development to develop present guidelines. An expert panel was established, which included clinicians, researchers, program directors, and methodologists. An independent group conducted systematic reviews and produced evidence summaries following the GRADE approach. GRADE evidence profiles were created for 16 key questions about the effects of cryotherapy in the presence of histologically confirmed CIN compared with no treatment and with loop electrosurgical excision procedure, as well as the use of different cryotherapy techniques. We identified a small number of randomized controlled trials or independently controlled observational studies. Surrogate outcomes were reported when evidence about outcomes critical to decision making were not available. The panel made 14 recommendations and documented factors that determined the strength and direction of the recommendations in decision tables. The present document summarizes new evidence-based WHO recommendations about the use of cryotherapy in women with histologically confirmed CIN for low-, middle-, and high-income countries. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.

PubMed

Wong, Jacqueline M K; Liu, Dachao; Lurain, John R

2014-01-01

To analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy. Of 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes. Twenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively. Multiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia.

PubMed

ElNaggar, Adam C; Santoso, Joseph T; Xie, Huiwen Bill

2012-02-01

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women. We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy. 133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was -0.0213 (95% CI=-0.128-0.086). Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic=-0.0213). Copyright © 2011 Elsevier Inc. All rights reserved.

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.

PubMed Central

Watanapa, P.; Williamson, R. C.

1993-01-01

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia. PMID:8494719

Screening for oesophageal neoplasia in patients with head and neck cancer

PubMed Central

Scherübl, H; Lampe, B von; Faiss, S; Däubler, P; Bohlmann, P; Plath, T; Foss, H-D; Scherer, H; Strunz, A; Hoffmeister, B; Stein, H; Zeitz, M; Riecken, E-O

2002-01-01

Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3 cm throughout the entire length of the squamous oesophagus. Low- or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group. British Journal of Cancer (2002) 86, 239–243. DOI: 10.1038/sj/bjc/6600018 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11870513

Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

PubMed Central

Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

2015-01-01

Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

Sample entropy analysis of cervical neoplasia gene-expression signatures

PubMed Central

Botting, Shaleen K; Trzeciakowski, Jerome P; Benoit, Michelle F; Salama, Salama A; Diaz-Arrastia, Concepcion R

2009-01-01

Background We introduce Approximate Entropy as a mathematical method of analysis for microarray data. Approximate entropy is applied here as a method to classify the complex gene expression patterns resultant of a clinical sample set. Since Entropy is a measure of disorder in a system, we believe that by choosing genes which display minimum entropy in normal controls and maximum entropy in the cancerous sample set we will be able to distinguish those genes which display the greatest variability in the cancerous set. Here we describe a method of utilizing Approximate Sample Entropy (ApSE) analysis to identify genes of interest with the highest probability of producing an accurate, predictive, classification model from our data set. Results In the development of a diagnostic gene-expression profile for cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix, we identified 208 genes which are unchanging in all normal tissue samples, yet exhibit a random pattern indicative of the genetic instability and heterogeneity of malignant cells. This may be measured in terms of the ApSE when compared to normal tissue. We have validated 10 of these genes on 10 Normal and 20 cancer and CIN3 samples. We report that the predictive value of the sample entropy calculation for these 10 genes of interest is promising (75% sensitivity, 80% specificity for prediction of cervical cancer over CIN3). Conclusion The success of the Approximate Sample Entropy approach in discerning alterations in complexity from biological system with such relatively small sample set, and extracting biologically relevant genes of interest hold great promise. PMID:19232110

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

2015-02-01

The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

Atrial Fibrillation and Colonic Neoplasia in African Americans.

PubMed

Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z; Ashktorab, Hassan

2015-01-01

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7-1.6, P = 0.7) were not significantly associated AF compared to control group. AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.

Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia.

PubMed

Bogani, Giorgio; Martinelli, Fabio; Ditto, Antonino; Taverna, Francesca; Lombardo, Claudia; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Fontanella, Caterina; Sabatucci, Ilaria; Borghi, Chiara; Recalcati, Dario; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2017-03-01

High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Detection of microinvasion in vulvar and cervical intraepithelial neoplasia using double immunostaining for cytokeratin and basement membrane components.

PubMed

Rush, Demaretta; Hyjek, Elizabeth; Baergen, Rebecca N; Ellenson, Lora H; Pirog, Edyta C

2005-06-01

Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls. To examine the utility of double immunostaining for cytokeratin-collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3. The study group consisted of 10 cases of "VIN 3, suspicious for invasion" and 10 cases of "CIN 3, suspicious for invasion." The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections. The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases "suspicious for invasion." Double immunostaining for cytokeratin- collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3.

Germ line mutation analysis in families with multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma.

PubMed

Karga, H J; Karayianni, M K; Linos, D A; Tseleni, S C; Karaiskos, K D; Papapetrou, P D

1998-10-01

The RET proto-oncogene has been identified as the multiple endocrine neoplasia type 2 disease gene. An association between specific RET mutation and disease phenotype has been reported. We present the phenotype-genotype of 12 Greek families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (FMTC). Seventy members were studied and DNA analysis for RET mutations was performed in fifty-eight of them. Exons 10, 11, 13, 14 and 16 of the RET proto-oncogene were analyzed by single strand conformation polymorphism analysis, direct DNA sequencing and/or restriction enzyme analysis. No mutations of the RET proto-oncogene were identified in 1 of 9 families with MEN 2A and in the 3 families with FMTC. In 7 MEN 2A families, the mutation was demonstrated in codon 634 and in 1 family it was demonstrated in codon 620. There was a low frequency, about 8%, of hyperparathyroidism associated with MEN 2A. The specific causative mutations for pararthyroid disease were C634R or C634Y. Among the MEN 2A individuals there was one case with de novo C634R mutation and one case, C634Y, with cutaneous lichen amyloidosis which predated by 24 years the diagnosis of MEN 2A. In 2 children who were MEN 2A gene carriers, microscopic medullary thyroid carcinomas were found. These data show a low frequency of hyperparathyroidism in our cases and provide further evidence that individuals with C634R as well as with C634Y mutations of the RET proto-oncogene could be at risk for parathyroid disease. Cutaneous lichen amyloidosis could be an early feature of MEN 2A. Additionally, direct DNA testing provided an opportunity to resect medullary thyroid carcinoma at an early stage.

Possible etiologic heterogeneity of vulvar intraepithelial neoplasia. A correlation of pathologic characteristics with human papillomavirus detection by in situ hybridization and polymerase chain reaction.

PubMed

Park, J S; Jones, R W; McLean, M R; Currie, J L; Woodruff, J D; Shah, K V; Kurman, R J

1991-03-15

A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the beta-globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a "condylomatous" appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus-16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV-positive women were younger than HPV-negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles.

In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini Faith; Bentley, David L.; Besselsen, David; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

2013-03-01

Our goal is to use optical coherence tomography (OCT) and multiphoton microscopy (MPM) to detect early tumor development in a mouse model of ovarian neoplasia. We hope to use information regarding early tumor development to create a diagnostic test for high-risk patients. In this study we collect in vivo images using OCT, second harmonic generation and two-photon excited fluorescence from non-vinylcyclohexene diepoxide (VCD)-dosed and VCD-dosed mice. VCD causes follicular apoptosis (simulating menopause) and leads to tumor development. Using OCT and MPM we visualized the ovarian microstructure and were able to see differences between non-VCD-dosed and VCD-dosed animals. This leads us to believe that OCT and MPM may be useful for detecting changes due to early tumor development.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings

PubMed Central

Zewdie, Getie A.; Cox, Dennis D.; Neely Atkinson, E.; Cantor, Scott B.; MacAulay, Calum; Davies, Kalatu; Adewole, Isaac; Buys, Timon P. H.; Follen, Michele

2012-01-01

Abstract. Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training. PMID:22559693

Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

PubMed Central

Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

2013-01-01

Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

PubMed

de Witte, C J; van de Sande, A J M; van Beekhuizen, H J; Koeneman, M M; Kruse, A J; Gerestein, C G

2015-11-01

Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

9 CFR 319.300 - Chili con carne.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of meat...

Mincle Signaling Promotes Con-A Hepatitis

PubMed Central

Greco, Stephanie H.; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R.; Nagaraj, Savitha V.; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E.; Katz, Steven C.; Miller, George

2016-01-01

Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. PMID:27559045

Mincle Signaling Promotes Con A Hepatitis.

PubMed

Greco, Stephanie H; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R; Nagaraj, Savitha V; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E; Katz, Steven C; Miller, George

2016-10-01

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPβ and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ-related signaling intermediates C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPβ and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. Copyright © 2016 by The American Association of Immunologists, Inc.

FLOCK cluster analysis of plasma cell flow cytometry data predicts bone marrow involvement by plasma cell neoplasia.

PubMed

Dorfman, David M; LaPlante, Charlotte D; Li, Betty

2016-09-01

We analyzed plasma cell populations in bone marrow samples from 353 patients with possible bone marrow involvement by a plasma cell neoplasm, using FLOCK (FLOw Clustering without K), an unbiased, automated, computational approach to identify cell subsets in multidimensional flow cytometry data. FLOCK identified discrete plasma cell populations in the majority of bone marrow specimens found by standard histologic and immunophenotypic criteria to be involved by a plasma cell neoplasm (202/208 cases; 97%), including 34 cases that were negative by standard flow cytometric analysis that included clonality assessment. FLOCK identified discrete plasma cell populations in only a minority of cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (38/145 cases; 26%). Interestingly, 55% of the cases negative by standard analysis, but containing a FLOCK-identified discrete plasma cell population, were positive for monoclonal gammopathy by serum protein electrophoresis and immunofixation. FLOCK-identified and quantitated plasma cell populations accounted for 3.05% of total cells on average in cases positive for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria, and 0.27% of total cells on average in cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (p<0.0001; area under the curve by ROC analysis=0.96). The presence of a FLOCK-identified discrete plasma cell population was predictive of the presence of plasma cell neoplasia with a sensitivity of 97%, compared with only 81% for standard flow cytometric analysis, and had specificity of 74%, PPV of 84% and NPV of 95%. FLOCK analysis, which has been shown to provide useful diagnostic information for evaluating patients with suspected systemic mastocytosis, is able to identify neoplastic plasma cell populations analyzed by flow cytometry, and may be helpful in the diagnostic

The Spatial Predilection for Early Esophageal Squamous Cell Neoplasia: A "Hot Zone" for Endoscopic Screening and Surveillance.

PubMed

Wang, Wen-Lun; Chang, I-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Lin, Jaw-Town; Mo, Lein-Ray; Wang, Hsiu-Po; Lee, Ching-Tai

2016-04-01

Early esophageal squamous cell neoplasias (ESCNs) are easily missed with conventional white-light endoscopy. This study aimed to assess whether early ESCNs have a spatial predilection and the patterns of recurrence after endoscopic treatment. We analyzed the circumferential and longitudinal location of early ESCNs, as well as their correlations with exposure to carcinogens in a cohort of 162 subjects with 248 early ESCNs; 219 of which were identified by screening and 29 by surveillance endoscopy. The circumferential location was identified using a clock-face orientation, and the longitudinal location was identified according to the distance from the incisor. The most common circumferential and longitudinal distributions of the early ESCNs were found in the 6 to 9 o'clock quadrant (38.5%) and at 26 to 30 cm from the incisor (41.3%), respectively. A total of 163 lesions (75%) were located in the lower hemisphere arc, and 149 (68.4%) were located at 26 to 35 cm from the incisor. One hundred eleven (51%) early ESCNs were centered within the "hot zone" (i.e., lower hemisphere arc of the esophagus at 26 to 35 cm from the incisor), which comprised 20% of the esophageal area. Exposure to alcohol, betel nut, or cigarette was risk factors for the development of early ESCNs in the lower hemisphere. After complete endoscopic treatment, the mean annual incidence of metachronous tumors was 10%. In addition, 43% of the metachronous recurrent neoplasias developed within the "hot zone." Cox regression analysis revealed that the index tumor within the hot zone (hazard ratio [HR]: 3.19; 95% confidence interval [CI]: 1.17-8.68; P = 0.02) and the presence of numerous Lugol-voiding lesions in the esophageal background mucosa were independent predictors for metachronous recurrence (HR: 4.61; 95% CI: 1.36-15.56; P = 0.01). We identified a hot zone that may be used to enhance the detection of early ESCNs during endoscopic screening and surveillance, especially in areas that

High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia

NASA Astrophysics Data System (ADS)

Shin, Dongsuk

Esophageal cancer is the eighth most common cancer in the world. Cancers of the esophagus account for 3.8% of all cases of cancers, with approximately 482,300 new cases reported in 2008 worldwide. In the United States alone, it is estimated that approximately 18,000 new cases will be diagnosed in 2013, and 15,210 deaths are expected. Despite advances in surgery and chemoradiation therapy, these advances have not led to a significant increase in survival rates, primarily because diagnosis often at an advanced and incurable stage when treatment is more difficult and less successful. Accurate, objective methods for early detection of esophageal neoplasia are needed. Here, quantitative classification algorithms for high resolution miscroendoscopic images were developed to distinguish between esophageal neoplastic and non-neoplastic tissue. A clinical study in 177 patients with esophageal squamous cell carcinoma (ESCC) was performed to evaluate the diagnostic performance of the classification algorithm in collaboration with the Mount Sinai Medical Center in the United States, the First Hospital of Jilin University in China, and the Cancer Institute and Hospital, the Chinese Academy of Medical Science in China. The study reported a sensitivity and specificity of 93% and 92%, respectively, in the training set, 87% and 97%, respectively, in the test set, and 84% and 95%, respectively, in an independent validation set. Another clinical study in 31 patients with Barrett's esophagus resulted in a sensitivity of 84% and a specificity of 85%. Finally, a compact, portable version of the high resolution microendoscopy (HRME) device using a consumer-grade camera was developed and a series of biomedical experimental studies were carried out to assess the capability of the device.

PROSPECTIVE COMPARISON OF TUMOR STAGING USING COMPUTED TOMOGRAPHY VERSUS MAGNETIC RESONANCE IMAGING FINDINGS IN DOGS WITH NASAL NEOPLASIA: A PILOT STUDY.

PubMed

Lux, Cassie N; Culp, William T N; Johnson, Lynelle R; Kent, Michael; Mayhew, Philipp; Daniaux, Lise A; Carr, Alaina; Puchalski, Sarah

2017-05-01

Identification of nasal neoplasia extension and tumor staging in dogs is most commonly performed using computed tomography (CT), however magnetic resonance imaging (MRI) is routinely used in human medicine. A prospective pilot study enrolling six dogs with nasal neoplasia was performed with CT and MRI studies acquired under the same anesthetic episode. Interobserver comparison and comparison between the two imaging modalities with regard to bidimensional measurements of the nasal tumors, tumor staging using historical schemes, and assignment of an ordinal scale of tumor margin clarity at the tumor-soft tissue interface were performed. The hypotheses included that MRI would have greater tumor measurements, result in higher tumor staging, and more clearly define the tumor soft tissue interface when compared to CT. Evaluation of bone involvement of the nasal cavity and head showed a high level of agreement between CT and MRI. Estimation of tumor volume using bidimensional measurements was higher on MRI imaging in 5/6 dogs, and resulted in a median tumor volume which was 18.4% higher than CT imaging. Disagreement between CT and MRI was noted with meningeal enhancement, in which two dogs were positive for meningeal enhancement on MRI and negative on CT. One of six dogs had a higher tumor stage on MRI compared to CT, while the remaining five agreed. Magnetic resonance imaging resulted in larger bidimensional measurements and tumor volume estimates, along with a higher likelihood of identifying meningeal enhancement when compared to CT imaging. Magnetic resonance imaging may provide integral information for tumor staging, prognosis, and treatment planning. © 2017 American College of Veterinary Radiology.

Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology

NASA Astrophysics Data System (ADS)

Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.

2014-03-01

It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.

DNA methylation as an adjunct to histopathology to detect prevalent, inconspicuous dysplasia and early-stage neoplasia in Barrett’s esophagus

PubMed Central

Alvi, Muhammad A; Liu, Xinxue; O’Donovan, Maria; Newton, Richard; Wernisch, Lorenz; Shannon, Nicholas B; Shariff, Kareem; di Pietro, Massimiliano; Bergman, Jacques J G H M; Ragunath, Krish; Fitzgerald, Rebecca C

2016-01-01

Purpose Endoscopic surveillance of Barrett’s esophagus (BE) is problematic because dysplasia/early-stage neoplasia are frequently invisible and likely to be missed due to sampling bias. Molecular abnormalities may be more diffuse than dysplasia. The aim was therefore to test whether DNA methylation; especially on imprinted and X-chromosome genes; is able to detect dysplasia/early-stage neoplasia. Experimental design 27K methylation arrays were used to find genes best able to differentiate between 22 BE and 24 esophageal adenocarcinoma (EAC) samples. These were validated using pyrosequencing on a retrospective cohort (60 BE, 36 dysplastic and 90 EAC) and then in a prospective multicenter study (98 BE patients, including 28 dysplastic and 9 early EAC) designed to utilize biomarkers to stratify patients according to their prevalent dysplasia/EAC status. Results 23% genes on the array, including 7% of X-linked and 69% of imprinted genes, demonstrated statistically significant changes in methylation in EAC vs. BE (Wilcoxon P<0.05). 6/7 selected candidate genes were successfully internally (Pearson’s P<0.01) and externally validated (ANOVA P<0.001). Four genes (SLC22A18, PIGR, GJA12 and RIN2) showed the greatest area under curve (0.988) to distinguish between BE and dysplasia/EAC in the retrospective cohort. This methylation panel was able to stratify patients from the prospective cohort into three risk groups based on the number of genes methylated (low risk: <2 genes, intermediate: 2 and high: >2). Conclusion Widespread DNA methylation changes were observed in Barrett’s carcinogenesis including ≈70% of known imprinted genes. A four-gene methylation panel stratified BE patients into three risk groups with potential clinical utility. PMID:23243219

Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors, and outcomes.

PubMed

Wang, Yao-Kuang; Chuang, Yun-Shiuan; Wu, Tzung-Shiun; Lee, Ka-Wo; Wu, Che-Wei; Wang, Hsiang-Chen; Kuo, Chie-Tong; Lee, Chien-Hung; Kuo, Wen-Rei; Chen, Chung-Ho; Wu, Deng-Chyang; Wu, I-Chen

2017-11-15

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1 and 10.9 for former and current drinkers, respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx. © 2017 UICC.

Performance of a risk index for advanced proximal colorectal neoplasia among a racially/ethnically diverse patient population (risk index for advanced proximal neoplasia).

PubMed

Levitzky, Benjamin E; Brown, Colin C; Heeren, Timothy C; Schroy, Paul C

2011-06-01

Tailoring the use of screening colonoscopy based on the risk of advanced proximal neoplasia (APN) has been advocated as a strategy for reducing demand and optimizing effectiveness. A 7-point index based on age, sex, and distal findings at sigmoidoscopy has been proposed that stratifies individuals into low, intermediate, and high-risk categories. The aim of this cross-sectional analysis was to determine the validity of this index, which was originally derived and validated among mostly whites, for black and Hispanic patients. Data, including age, sex, colonoscopic findings, and pathology, were collected retrospectively from 1,481 white, 1,329 black, and 689 Hispanic asymptomatic, average-risk patients undergoing screening colonoscopy between 2000 and 2005. Cumulative scores ranging from 0 to 7 were derived for each subject and categorized as low, intermediate, or high risk. Rates of APN were assessed for each risk category after stratification by race/ethnicity. Index performance was assessed using the C-statistic and compared across the three racial groups. Rates of APN among patients categorized as low, intermediate, or high risk increased from 1.0 to 2.8 to 3.7% for whites, 1.0 to 2.2 to 4.2% for blacks, and 0.6 to 1.9 to 3.7% for Hispanics. The index performed similarly for all three groups, but showed limited ability to discriminate low from intermediate-risk patients, with C-statistic values of 0.62 for whites, 0.63 for blacks, and 0.68 for Hispanics. A risk index based on age, sex, and distal endoscopic findings has limited ability to discriminate low from intermediate-risk white, black, and Hispanic patients for APN.

Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias

PubMed Central

Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo

2000-01-01

High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549

[Behavior of cervical intraepithelial neoplasia in pregnant adolescents and its persistence after an obstetric event].

PubMed

Machain-Loera, Alfredo; Jiménez-Rodríguez, Antonio; Huerta-Casillas, Félix Rafael; Barajas-Serrano, Tanya Lizbeth; Barrera-de León, Juan Carlos

2014-12-01

To observe the behavior of cervical intraepithelial neoplasia in pregnant adolescents and the persistence before the delivery. A cross-sectional study including 47 pregnant adolescents with NIC-positive results diagnosed by colposcopy during pregnancy with subsequent evaluation before the delivery. Nonrandom sampling of consecutive cases. Descriptive statistics with central and dispersal measures. In total, 156 pregnant adolescents were studied, of which 30% (n = 47) had positive results to NIC with subsequent evaluation. Ages 18 ± 1.5 years, primiparous 77%, sexual activity initiation 15.6 ± 1.6 years old, sexual partners 1 (1-6), smoking and alcoholism 21%. At the beginning of pregnancy, 98% had NIC I results and 2% had NIC II by colposcopy. After delivery, 13% had normal results and 87% remained in NIC I. The findings suggest that in pregnant adolescents there exists a natural dysplasia history as in pregnant women. Most of the lesions are NIC I and don't modify the evolution, with some regressing after the delivery.

[Specifics of hormonal and energy balance in patients with hyperplasia and endometrial neoplasia with metabolic syndrome in the background].

PubMed

Chernyshova, A L; Kolomiets, L A; Bochkarëva, N V; Kondakova, I V

2013-01-01

We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.

Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

USGS Publications Warehouse

House, M.L.; Kim, C.H.; Reno, P.W.

1998-01-01

Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

Epidemiology of neoplasia in captive black-footed ferrets (Mustela nigripes), 1986-1996.

PubMed

Lair, Stéphane; Barker, Ian K; Mehren, Kay G; Williams, Elizabeth S

2002-09-01

The epidemiology of neoplastic disease was studied retrospectively in the captive population of black-footed ferrets (Mustela nigripes). Postmortem reports were reviewed and archived tissues examined from 184 of the 227 adult (>1 yr old) black-footed ferrets that died from the beginning of the current captive propagation program in late 1985 to the end of 1996. A total of 185 neoplasms, of 28 distinct phenotypes, were seen in 102 (55.4%) of these ferrets. There was more than one tumor type present in 51 ferrets. Tumors of the apocrine glands (28.3%), renal tubular neoplasms (20.7%), and biliary cystadenoma or carcinoma (20.1%) were the most common neoplasms. The probability of developing most types of neoplasms increased with age. Neoplasms of the apocrine glands were more common in males and may be hormonally influenced. The unusually high prevalence of biliary cystadenocarcinoma may be secondary to the common occurrence of intrahepatic biliary cysts in this population. Although neoplasia is an important cause of mortality in captive adult black-footed ferrets, its impact on captive propagation of the species, and on the wild population, is probably limited because clinically significant tumors are encountered almost exclusively in postreproductive ferrets (>3 yr old) and because ferrets released into their natural habitat rarely reach susceptible age.

Women in Combat Pros and Cons

DTIC Science & Technology

1988-04-01

and Cons . Major Thomas H. Cecil 88-0490 "--"insights into tomorrou,"’ ..v- A A 0 PtY-i f(.> i’I,-:::x:’~ --pcr~ j.~ ~~* --. -- iiV • DISCLAIMER The...k. r- r,’ I’. REPORT NUMBER 88-0490 TITLE WOMEN IN COMBAT-PROS AND CONS AUTHOR(S) MAJOR THOMAS H. CEC-IL, USAF -% FACULTY ADVISOR CH, LT COL DAVID W...NUMBERS 11 TITLE (include Security Classification) WOMEN IN COMBAT--PROS AND CONS 12. PERSON4AL AUTHOR(S) Cecil, Thomas H1., Major, USAF 9a YýOF REPORT

Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus).

PubMed

LePage, Véronique; Dutton, Christopher J; Kummrow, Maya; McLelland, David J; Young, Karrie; Lumsden, John S

2012-03-01

Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids.

[Shall all lobular intraepithelial neoplasia diagnosed on image-guided biopsy require a surgical management?].

PubMed

Fischer-Hunsinger, Maeva; Guinebretière, Jean-Marc; Lasry, Serge; Langer, Adriana; Berment, Hélène; Nekka, Ibtissem; Nodiot, Philippe; Cherel, Pascal

2016-05-01

Lobular intraepithelial neoplasia (LIN) diagnosed on image-guided biopsy may be associated with an undiagnosed cancer. This is called under-diagnosis. The consequence is that management of these lesions is often surgical. But many surgeries finally are unnecessary. The aim of our study was to define criteria to avoid unnecessary surgery. This is a single-center, retrospective after a database collected prospectively study. Fourteen thousand biopsies were analyzed, including 456 diagnosed NLI. Under-diagnosis rates were analyzed according to many criteria. The average duration of following was 45 months. For atypical lobular hyperplasia (ALH), we obtained 7.6% under-diagnosis and combining several criteria, we got a low risk of cancer (2%). For LCIS, this rate was 23% and any low-risk group could be identified. ALH with calcifications≤20 mm, without any atypical lesion associated, histologically focal and whose removal is representative may be safely observed. For other LIN, surgery remains indicated. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Wide-field and high-resolution optical imaging for early detection of oral neoplasia

NASA Astrophysics Data System (ADS)

Pierce, Mark C.; Schwarz, Richard A.; Rosbach, Kelsey; Roblyer, Darren; Muldoon, Tim; Williams, Michelle D.; El-Naggar, Adel K.; Gillenwater, Ann M.; Richards-Kortum, Rebecca

2010-02-01

Current procedures for oral cancer screening typically involve visual inspection of the entire tissue surface at risk under white light illumination. However, pre-cancerous lesions can be difficult to distinguish from many benign conditions when viewed under these conditions. We have developed wide-field (macroscopic) imaging system which additionally images in cross-polarized white light, narrowband reflectance, and fluorescence imaging modes to reduce specular glare, enhance vascular contrast, and detect disease-related alterations in tissue autofluorescence. We have also developed a portable system to enable high-resolution (microscopic) evaluation of cellular features within the oral mucosa in situ. This system is a wide-field epi-fluorescence microscope coupled to a 1 mm diameter, flexible fiber-optic imaging bundle. Proflavine solution was used to specifically label cell nuclei, enabling the characteristic differences in N/C ratio and nuclear distribution between normal, dysplastic, and cancerous oral mucosa to be quantified. This paper discusses the technical design and performance characteristics of these complementary imaging systems. We will also present data from ongoing clinical studies aimed at evaluating diagnostic performance of these systems for detection of oral neoplasia.

Effect of race/ethnicity on clinical presentation and risk of gestational trophoblastic neoplasia in patients with complete and partial molar pregnancy at a tertiary care referral center.

PubMed

Gockley, Allison A; Joseph, Naima T; Melamed, Alexander; Sun, Sue Yazaki; Goodwin, Benjamin; Bernstein, Marilyn; Goldstein, Donald P; Berkowitz, Ross S; Horowitz, Neil S

2016-09-01

The reported incidence of molar pregnancy varies widely among different geographic locations. This variation has been attributed, at least in part, to racial/ethnic differences. While the incidence of molar pregnancies is decreasing, certain ethnic groups such as Hispanics, Asians, and American Indians continue to have an increased risk of developing gestational trophoblastic disease across the globe. We sought to describe the potential effect of ethnicity/race on the presentation and clinical course of complete mole and partial mole. All patients followed up for complete mole and partial mole at a single institution referral center from 1994 through 2013 were identified. Variables including age, race, gravidity, parity, gestational age, presenting signs/symptoms, serum human chorionic gonadotropin values, and development of gestational trophoblastic neoplasia were extracted from medical records and patient surveys. Patients with complete mole and partial mole were categorized into race/ethnicity groups defined as white, black, Asian, or Hispanic. Due to low numbers of non-white patients with partial mole in each non-white category, patients with partial mole were grouped as white or non-white. Continuous variables were compared using the Kruskal-Wallis test and binary variables were compared using the Fisher exact test. A total of 167 complete mole patients with known race/ethnicity status were included (57.48% white, 14.97% Asian, 14.37% black, 13.17% Hispanic). Hispanics presented at younger age (median 24.5 years) compared to whites (median 32.0 years, P = .04) and Asians (median 31.0 years, P = .03). Blacks had higher gravidity than whites (P < .001) and Hispanics (P = .05). There was no significant difference in presenting symptoms, gestational age at diagnosis, and preevacuation serum human chorionic gonadotropin level by race/ethnicity. Hispanics were significantly less likely than whites to develop gestational trophoblastic neoplasia (absolute risk

Protective effect of zinc on N-methyl-N-nitrosourea and testosterone-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley rats.

PubMed

Banudevi, Sivanantham; Elumalai, Perumal; Sharmila, Govindaraj; Arunkumar, Ramachandran; Senthilkumar, Kalimuthu; Arunakaran, Jagadeesan

2011-09-01

Previous studies have suggested that zinc exerts anticarcinogenic and antiproliferative effects against prostate cancer both in vitro and in rat ventral prostate. Zinc accumulation diminishes early in the course of prostate malignancy and it inhibits the growth of several carcinoma cells through induction of cell cycle arrest and apoptosis. In this study, we have investigated the influence of zinc on N-methyl-N-nitrosourea (MNU) and testosterone (T)-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley (SD) rats. The results indicate that zinc plays an important role in prostate carcinogenesis. Increased tumor incidence was accompanied by a decrease in prostatic acid phosphatase activity, citrate, zinc, glutathione-S-transferase, reduced glutathione, p53, B-cell lymphoma protein (Bcl-2)-associated X protein and caspase-3 levels in MNU + T-treated rats. On the contrary, significantly increased phase I drug metabolizing enzyme activities, lipid peroxide, hydrogen peroxide, proliferating cell nuclear antigen, Bcl-2 and Bcl-X(L) protein levels were observed in the dorsolateral prostate of MNU + T-treated rats. Simultaneous zinc supplementation significantly reversed these effects in MNU + T-treated rats. Signs of dysplasia, a characteristic of prostatic intraepithelial neoplasia, were evident in the dorsolateral prostatic tissue sections by MNU + T administration. However, zinc supplementation has reversed these effects in the dorsolateral prostatic histoarchitecture. These results suggest that zinc may act as an essential trace element against MNU and testosterone-induced prostatic preneoplastic progression in SD rats.

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

PubMed

Hillemanns, P; Untch, M; Dannecker, C; Baumgartner, R; Stepp, H; Diebold, J; Weingandt, H; Pröve, F; Korell, M

2000-03-01

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat. Copyright 2000 Wiley-Liss, Inc.

Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

PubMed

Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

2015-09-01

To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Predictors of advanced colorectal neoplasia for colorectal cancer screening.

PubMed

Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y

2014-05-01

The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, p<0.001); overweight (BMI=23-24.9, AOR=1.52, 95% CI=1.12, 2.07, p=0.007); obesity (BMI≥25, AOR=1.56, 95% CI=1.15, 2.10, p=0.004); hypertension (AOR=1.58, 95% CI=1.21, 2.06, p=0.001); and alcohol consumption (AOR=1.47, 95% CI=1.05, 2.06, p=0.025) were associated with ACN. The c-statistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.

Anal intraepithelial neoplasia: A review of diagnosis and management

PubMed Central

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-01-01

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations. PMID:28255426

Anal intraepithelial neoplasia: A review of diagnosis and management.

PubMed

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-02-15

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

PubMed

Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique

2017-03-15

To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

PubMed

Gordillo, Jordi; Cabré, Eduard; Garcia-Planella, Esther; Ricart, Elena; Ber-Nieto, Yolanda; Márquez, Lucía; Rodríguez-Moranta, Francisco; Ponferrada, Ángel; Vera, Isabel; Gisbert, Javier P; Barrio, Jesús; Esteve, Maria; Merino, Olga; Muñoz, Fernando; Domènech, Eugeni

2015-12-01

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms.

PubMed

van Beurden, M.; van Der Vange, N.; ten Kate, F. J. W.; de Craen, A. J. M.; Schilthuis, M. S.; Lammes, F. B.

1998-01-01

van Beurden M, van der Vange N, ten Kate FJW, de Craen AJM, Schilthuis MS, Lammes FB. Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms. Int J Gynecol Cancer 1998; 8: 73-77. A study was undertaken to determine the effectiveness of extensive and restricted surgery for vulvar intraepithelial neoplasia (VIN) 3. All consecutive patients with VIN 3 admitted to a tertiary referral hospital were included. The main outcome measures were relief and recurrence of symptoms and progression to invasive disease in patients with VIN 3 after extensive or restricted surgery. Of every vulvoscopic visible lesion a biopsy was taken to establish extent and grade of VIN and to rule out invasive carcinoma. Patients with unifocal VIN 3 underwent extensive surgery. Patients with multifocal VIN 3 underwent extensive or restricted surgery or an expectant management was adopted, depending on the existence of symptoms and the presence of invasive vulvar carcinoma. Forty-seven patients were evaluated. Eighty-three percent of patients had a long history of symptoms. Eight patients (17%) had unifocal VIN 3. In 9% of the patients a superficially invasive vulvar carcinoma was found, ie with a depth of invasion of 1 mm or less. Only 20% of the extensively operated patients had free surgical margins. There was recurrence of symptoms in all of the extensively operated patients, in contrast to a 26% persistence or recurrence rate of symptoms in the restrictedly operated patients. In patients with multifocal VIN 3 who underwent restricted surgery, young age of the patient (P = 0.02) and large extension of VIN 3 (P = 0.02) were significant factors in predicting persistence or recurrence of symptoms. Only once was a superficially invasive vulvar carcinoma diagnosed during follow-up, and this was in an extensively operated patient. Vulvoscopically directed biopsies in VIN 3 are a safe method to exclude invasive disease. Restricted

A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A.

PubMed

Bethanis, Sotirios; Koutsodontis, George; Palouka, Theodosia; Avgoustis, Christos; Yannoukakos, Drakoulis; Bei, Thalia; Papadopoulos, Savas; Linos, Dimitrios; Tsagarakis, Stylianos

2007-01-01

Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.

Associations of dietary fat with risk of early neoplasia in the proximal colon in a population-based case-control study.

PubMed

Mo, Allen; Wu, Rong; Grady, James P; Hanley, Matthew P; Toro, Margaret; Swede, Helen; Devers, Thomas J; Hartman, Terryl J; Rosenberg, Daniel W

2018-07-01

Excess dietary fat consumption is strongly associated with the risk of colorectal cancer, but less is known about its role in the earliest stages of carcinogenesis, particularly within the proximal colon. In the following case-control study, we evaluated the relationship between the intake of dietary fats and the frequency of early proximal neoplasia [aberrant crypt foci (ACF) or polyps], detectable by high-definition colonoscopy with contrast dye-spray. Average-risk screening individuals underwent a high-definition colonoscopy procedure as part of larger ongoing clinical study of precancerous lesions in the proximal colon. Dietary fat intake was assessed using the Block Brief Food Frequency Questionnaire, which estimates average dietary intake based on 70 food items. The diets of individuals with no endoscopically identifiable lesions (n = 36) were compared to those with either ACF or polyps detected in the proximal colon. In multivariate analysis, high dietary intake of total polyunsaturated fatty acids (PUFAs) and intake of omega-6 and omega-3 fatty acids were positively associated with neoplastic lesions in the proximal colon. When comparing ACF and polyp groups separately, a positive association was observed for both proximal polyps (OR 2.28; CI 1.16-7.09) and ACF (OR 2.86; CI 1.16-7.09) for total PUFA intake. Furthermore, the prevalence of proximal ACF was increased with higher intake of omega-6 (OR 3.54; CI 1.32-9.47) and omega-3 fatty acids (OR 2.29; CI 1.02-5.13), although there was no discernible difference in the omega-6/omega-3 ratio. These results suggest that dietary PUFAs may be positively associated with risk of early neoplasia in the proximal colon. This study provides further evidence that dietary PUFA composition may play an important role in altering the microenvironment within the human colon.

The Human Papillomavirus Vaccine: Current Perspective and Future Role in Prevention and Treatment of Anal Intraepithelial Neoplasia and Anal Cancer

PubMed Central

Mehta, Mudresh R.; Lewis, James S.; Lockhart, A. Craig

2016-01-01

The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are rising in the U.S. and globally. Five-year survival rates with current modalities of treatment for anal cancer are generally favorable for localized and regional disease. For metastatic disease, the relative survival rate is poor. Major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse (hetero- and homosexual), increasing HPV infections, and longer life expectancy of treated people who are seropositive for human immunodeficiency virus. Because treatment outcomes with systemic therapy in patients with advanced disease are so poor, prevention may be the best approach for reducing disease burden. The association of a major causative agent with anal cancer provides an excellent opportunity for prevention and treatment. The advent of the HPV vaccine for anal cancer prevention and treatment is a significant milestone and has the potential to greatly impact these cancers. The data regarding potential use of the HPV vaccine in anal cancer prevention and treatment are reviewed. Implications for Practice: The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are on the rise in the U.S. and globally. Based on recent studies, the HPV vaccine is approved for prevention of the infection and development of HPV-related anal cancer. In addition, several small studies have shown that the vaccine may be useful as adjuvant therapy for anal cancer. There is a need for public health strategies aimed at education of both patients and practitioners to improve the use of the vaccine for prevention of HPV-related anal cancer. The development of a therapeutic vaccine is a work in progress. PMID:26961923

IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth

PubMed Central

Ayars, Michael; O’Sullivan, Eileen; Macgregor-Das, Anne; Shindo, Koji; Kim, Haeryoung; Borges, Michael; Yu, Jun; Hruban, Ralph H.; Goggins, Michael

2017-01-01

Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (IL2RG) encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth in vivo. PMID:29137350

Fiber optic FTIR instrument for in vivo detection of colonic neoplasia

NASA Astrophysics Data System (ADS)

Van Nortwick, Matthew; Hargrove, John; Wolters, Rolf; Crawford, James M.; Arroyo, May; Mackanos, Mark; Contag, Christopher H.; Wang, Thomas D.

2009-02-01

We demonstrate the proof of concept for use of a fiber optic FTIR instrument to perform in vivo detection of colonic neoplasia as an adjunct to medical endoscopy. FTIR is sensitive to the molecular composition of tissue, and can be used as a guide for biopsy by identifying pre-malignant tissue (dysplasia). First, we demonstrate the use of a silver halide optical fiber to collect mid-infrared absorption spectra in the 950 to 1800 cm-1 regime with high signal-to-noise from biopsy specimens of colonic mucosa tissue ex vivo. We observed subtle differences in wavenumber and magnitude of the absorbance peaks over this regime. We then show that optimal sub-ranges can be defined within this spectral regime and that spectral pre-processing can be performed to classify the tissue as normal, hyperplasia, or dysplasia with high levels of performance. We used a partial least squares discriminant analysis and a leave-one-subject-out crossvalidation strategy to classify the spectra. The results were compared with histology, and the optimal thresholds resulted in an overall sensitivity, specificity, accuracy, and positive predictive value of 96%, 92%, 93%, and 82%, respectively for this technique. We demonstrate that mid-infrared absorption spectra can be collected remotely with an optical fiber and used to identify colonic dysplasia with high accuracy. We are now developing an endoscope compatible optical fiber to use this technique clinically for the early detection of cancer.

Ependimoma myxopapilar sacro gigante con osteolisis

PubMed Central

Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

2014-01-01

Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience.

PubMed

Paraskevaidis, E; Koliopoulos, G; Malamou-Mitsi, V; Zikopoulos, K; Paschopoulos, M; Pappa, L; Agnantis, N J; Loli, D E

2001-01-01

Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ). A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied. Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain. LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

PubMed

De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Planificación Neuroquirúrgica con Software Osirix

PubMed Central

Jaimovich, Sebastián Gastón; Guevara, Martin; Pampin, Sergio; Jaimovich, Roberto; Gardella, Javier Luis

2014-01-01

Introducción: La individualidad anatómica es clave para reducir el trauma quirúrgico y obtener un mejor resultado. Actualmente, el avance en las neuroimágenes ha permitido objetivar esa individualidad anatómica, permitiendo planificar la intervención quirúrgica. Con este objetivo, presentamos nuestra experiencia con el software Osirix. Descripción de la técnica: Se presentan 3 casos ejemplificadores de 40 realizados. Caso 1: Paciente con meningioma de la convexidad parasagital izquierda en área premotora; Caso 2: Paciente con macroadenoma hipofisario, operada previamente por vía transeptoesfenoidal en otra institución con una resección parcial; Caso 3: Paciente con lesiones en pedúnculo cerebeloso medio bilateral. Se realizó la planificación prequirúrgica con el software OsiriX, fusionando y reconstruyendo en 3D las imágenes de TC e IRM, para analizar relaciones anatómicas, medir distancias, coordenadas y trayectorias, entre otras funciones. Discusión: El software OsiriX de acceso libre y gratuito permite al cirujano, mediante la fusión y reconstrucción en 3D de imágenes, analizar la anatomía individual del paciente y planificar de forma rápida, simple, segura y económica cirugías de alta complejidad. En el Caso 1 se pudo analizar las relaciones del tumor con las estructuras adyacentes para minimizar el abordaje. En el Caso 2 permitió comprender la anatomía post-operatoria previa del paciente, para determinar la trayectoria del abordaje transnasal endoscópico y la necesidad de ampliar su exposición, logrando la resección tumoral completa. En el Caso 3 permitió obtener las coordenadas estereotáxicas y trayectoria de una lesión sin representación tomográfica. Conclusión: En casos de no contar con costosos sistemas de neuronavegación o estereotáxia el software OsiriX es una alternativa a la hora de planificar la cirugía, con el objetivo de disminuir el trauma y la morbilidad operatoria. PMID:25165617

Neoplasia of the ampulla of Vater. Ki-ras and p53 mutations.

PubMed Central

Scarpa, A.; Capelli, P.; Zamboni, G.; Oda, T.; Mukai, K.; Bonetti, F.; Martignoni, G.; Iacono, C.; Serio, G.; Hirohashi, S.

1993-01-01

Eleven tumors of the ampulla of Vater (5 stage IV and 2 stage II adenocarcinomas, 1 stage II papillary carcinoma, 1 neuroendocrine carcinoma, and 2 adenomas, one with foci of carcinoma) were examined for Ki-ras and p53 gene mutations by single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA fragments. Ki-ras mutations were found in one adenocarcinoma and in the adenoma with foci of carcinoma, both involving mainly the intraduodenal bile duct component of the ampulla. Seven cases showed p53 gene mutations: four advanced-stage adenocarcinomas, the papillary carcinoma, the neuroendocrine carcinoma, and the adenoma with foci of carcinoma. Nuclear accumulation of p53 protein was immunohistochemically detected in the morphologically high-grade areas of the five cancers harboring a p53 gene missense point mutation. The adenomas, the two frame shift-mutated cancers, and the adenomatous and low-grade cancer areas of mutated carcinomas were immunohistochemically negative. Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8475992

Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

PubMed

Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

1994-11-01

The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.

PubMed

Scurry, James; Campion, Michael; Scurry, Bonnie; Kim, Soo Nyung; Hacker, Neville

2006-04-01

There are 2 types of vulvar intraepithelial neoplasia (VIN): warty-basaloid and differentiated. Differentiated VIN is uncommon and seldom diagnosed prior to carcinoma and, traditionally, is not graded. There are currently 3 grading systems for warty-basaloid VIN: the World Health Organization (WHO) 3 grade system of VIN 1-3, a 2 grade system of low and high grade vulvar intraepithelial lesions, and the revised International Society for the Study of Vulvovaginal Disease (ISSVD) classification which has no grading of VIN. According to the ISSVD, VIN 1 should be abolished and VIN 2 and 3 combined into a single category, simply termed warty-basaloid VIN. To determine the best system for grading warty-basaloid VIN and learn more about differentiated VIN, we reviewed the pathology of 164 consecutive women with VIN. Of these, 134 (82.3%) had warty-basaloid VIN, 29 (18.2%) had differentiated VIN, and 1 had both. Of warty-basaloid VIN cases, 4 had VIN 1, 13 VIN 2, and 118 VIN 3 when graded according to the WHO. All VIN 1 occurred in condylomata acuminata. VIN 2 and 3 were distinguished only by degree of abnormality. Differentiated VIN was diagnosed before SCC in only 7 cases (26.7%). Because the only VIN 1 cases seen were in condylomata acuminata and because VIN 2 and 3 were difficult to distinguish and there appears little clinical reason to do so, our study supports the ISSVD proposal that VIN 1 be abolished and VIN 2 and 3 be combined. There needs to be more clinical awareness of vulvar conditions, so that differentiated VIN is biopsied before cancer has supervened.

Pros and Cons of International Weapons Procurement Collaboration.

DTIC Science & Technology

1995-01-01

ad- vanced U.S. industry. Greater risk of cost growth and schedule slippage. Pro: U.S. and partners share common equip- ment. Con : U.S. require...Mark A., 1947- Pros and cons of international weapons procurement collaboration / Mark Lorell, Julia Lowell, p. cm "Prepared for the Office...one/ Cons of International Weapons Procurement Collaboration Mark Lorell Julia Lowell National Defense Research Institute Prepared for the

Serological responses to papillomavirus group-specific antigens in women with neoplasia of the cervix uteri.

PubMed Central

Dillner, L; Moreno-Lopez, J; Dillner, J

1990-01-01

Certain types of human papillomaviruses have been linked to the development of carcinoma of the cervix uteri. We have analyzed 114 serum specimens from women with cervical intraepithelial neoplasia (CIN) or carcinoma of the cervix uteri for the presence of serum antibodies against purified, disrupted bovine papillomavirus (BPV). The titers of immunoglobulin A (IgA) antibodies against BPV were slightly elevated (P less than 0.025) in the sera from CIN or cervical carcinoma patients compared with the titers of 139 serum specimens from sex- and age-matched healthy controls. In contrast, both the IgG and IgM serum antibody titers against BPV were significantly decreased for CIN and cervical carcinoma patients compared with those of healthy controls (P less than 0.001 and P less than 0.005, respectively). These results suggest that the difference between IgA and IgG or IgM antibodies to papillomavirus group-specific antigens may represent interesting serological parameters that could possibly be used in the epidemiologic study of women at risk for CIN. PMID:2157738

Safety and efficacy of targeted hyperthermia treatment utilizing gold nanorod therapy in spontaneous canine neoplasia.

PubMed

Schuh, Elizabeth M; Portela, Roberta; Gardner, Heather L; Schoen, Christian; London, Cheryl A

2017-10-02

Hyperthermia is an established anti-cancer treatment but is limited by tolerance of adjacent normal tissues. Parenteral administration of gold nanorods (NRs) as a photosensitizer amplifies the effects of hyperthermia treatment while sparing normal tissues. This therapy is well tolerated and has demonstrated anti-tumor effects in mouse models. The purpose of this phase 1 study was to establish the safety and observe the anti-tumor impact of gold NR enhanced (plasmonic) photothermal therapy (PPTT) in client owned canine patients diagnosed with spontaneous neoplasia. Seven dogs underwent gold NR administration and subsequent NIR PPTT. Side effects were mild and limited to local reactions to NIR laser. All of the dogs enrolled in the study experienced stable disease, partial remission or complete remission. The overall response rate (ORR) was 28.6% with partial or complete remission of tumors at study end. PPTT utilizing gold nanorod therapy can be safely administered to canine patients. Further studies are needed to determine the true efficacy in a larger population of canine cancer patients and to and identify those patients most likely to benefit from this therapy.

Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peppa, Melpomeni, E-mail: molypepa@otenet.g; Brountzos, Elias; Economopoulos, Nicolaos

2009-07-15

Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and tomore » prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.« less

Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: a cross-sectional study.

PubMed

Sánchez-Lander, Jorge; Cortiñas, Paula; Loureiro, Carmen Luisa; Pujol, Flor Helene; Medina, Francisco; Capote-Negrín, Luis; Bianchi, Gino; García-Barriola, Victoria; Ruiz-Benni, Angela; Avilán-Rovira, José; Acosta, Humberto

2012-10-01

This study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela. Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types. HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P=0.0006). this is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

PubMed

Gargano, Julia W; Wilkinson, Edward J; Unger, Elizabeth R; Steinau, Martin; Watson, Meg; Huang, Youjie; Copeland, Glenn; Cozen, Wendy; Goodman, Marc T; Hopenhayn, Claudia; Lynch, Charles F; Hernandez, Brenda Y; Peters, Edward S; Saber, Maria Sibug; Lyu, Christopher W; Sands, Lauren A; Saraiya, Mona

2012-10-01

The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin-stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

Anakoinosis: Communicative Reprogramming of Tumor Systems - for Rescuing from Chemorefractory Neoplasia.

PubMed

Hart, Christina; Vogelhuber, Martin; Wolff, Daniel; Klobuch, Sebastian; Ghibelli, Lina; Foell, Jürgen; Corbacioglu, Selim; Rehe, Klaus; Haegeman, Guy; Thomas, Simone; Herr, Wolfgang; Reichle, Albrecht

2015-08-01

Disruptive technologies, such as communicative reprogramming (anakoinosis) with cellular therapies in situ for treating refractory metastatic cancer allow patient care to accelerate along a totally new trajectory and highlight what may well become the next sea change in the care of patients with many types of advanced neoplasia. Cellular therapy in situ consisted of repurposed drugs, pioglitazone plus all-trans retinoic acid or dexamethasone or interferon-alpha (dual transcriptional modulation) combined with metronomic low-dose chemotherapy or low-dose 5-azacytidine, plus/minus classic targeted therapy. The novel therapeutic tools for specifically designing communication processes within tumor diseases focus on redirecting (1) rationalizations of cancer hallmarks (constitution of single cancer hallmarks), (2) modular events, (3) the 'metabolism' of evolutionary processes (the sum of therapeutically and intrinsically inducible evolutionary processes) and (4) the holistic communicative context, which determines validity and denotation of tumor promoting communication lines. Published data on cellular therapies in situ (6 histologic tumor types, 144 patients, age 0.9-83 years) in castration-resistant prostate cancer, pretreated renal clear cell carcinoma, chemorefractory acute myelocytic leukemia, multiple myeloma > second-line, chemorefractory Hodgkin lymphoma or multivisceral Langerhans cell histiocytosis, outline the possibility for treating refractory metastatic cancer with the hope that this type of reprogrammed communication will be scalable with minimal toxicity. Accessibility to anakoinosis is a tumor inherent feature, and cellular therapy in situ addresses extrinsic and intrinsic drug resistance, by redirecting convergent organized communication tools, while been supported by quite different pattern of (molecular-)genetic aberrations.

SHP2 Is Required for BCR-ABL1-Induced Hematologic Neoplasia

PubMed Central

Gu, Shengqing; Sayad, Azin; Chan, Gordon; Yang, Wentian; Lu, Zhibin; Virtanen, Carl; Van Etten, Richard A.; Neel, Benjamin G.

2017-01-01

BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation (BMT) models for CML and BCR-ABL1+ B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia. Ptpn11 deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+ B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, is essential for BCR-ABL1+, but not WT, pre-B cell proliferation. The MEK/ERK pathway is regulated by SHP2 in WT and BCR-ABL1+ pre-B cells, but is only required for the proliferation of BCR-ABL1+ cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+ pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+ and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, represses MXD3/4 to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells. PMID:28804122

9 CFR 319.301 - Chili con carne with beans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

9 CFR 319.301 - Chili con carne with beans.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

9 CFR 319.301 - Chili con carne with beans.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

9 CFR 319.301 - Chili con carne with beans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

9 CFR 319.301 - Chili con carne with beans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

Analysis of Fecal DNA Methylation to Detect Gastrointestinal Neoplasia

PubMed Central

Tanaka, Noriaki; Cullings, Harry M.; Sun, Dong-Sheng; Sasamoto, Hiromi; Uchida, Takuyuki; Koi, Minoru; Nishida, Naoshi; Naomoto, Yoshio; Boland, C. Richard; Matsubara, Nagahide; Goel, Ajay

2009-01-01

Background The development of noninvasive screening tests is important to reduce mortality from gastrointestinal neoplasia. We sought to develop such a test by analysis of DNA methylation from exfoliated cancer cells in feces. Methods We first analyzed methylation of the RASSF2 and SFRP2 gene promoters from 788 primary gastric and colorectal tissue specimens to determine whether methylation patterns could act as stage-dependent biomarkers of gastrointestinal tumorigenesis. Next, we developed a novel strategy that uses single-step modification of DNA with sodium bisulfite and fluorescence polymerase chain reaction methodology to measure aberrant methylation in fecal DNA. Methylation of the RASSF2 and SFRP2 promoters was analyzed in 296 fecal samples obtained from a variety of patients, including 21 with gastric tumors, 152 with colorectal tumors, and 10 with non-neoplastic or inflammatory lesions in the gastrointestinal lumen. Results Analysis of DNA from tissues showed presence of extensive methylation in both gene promoters exclusively in advanced gastric and colorectal tumors. The assay successfully identified one or more methylated markers in fecal DNA from 57.1% of patients with gastric cancer, 75.0% of patients with colorectal cancer, and 44.4% of patients with advanced colorectal adenomas, but only 10.6% of subjects without neoplastic or active diseases (difference, gastric cancer vs undiseased  =  46.5%, 95% confidence interval (CI)  =  24.6% to 68.4%, P < .001; difference, colorectal cancer vs undiseased = 64.4%, 95% CI = 53.5% to 75.2%, P < .001; difference, colorectal adenoma vs undiseased = 33.8%, 95% CI = 14.2% to 53.4%, P < .001). Conclusions Methylation of the RASSF2 and SFRP2 promoters in fecal DNA is associated with the presence of gastrointestinal tumors relative to non-neoplastic conditions. Our novel fecal DNA methylation assay provides a possible means to noninvasively screen not only for colorectal tumors but also for gastric tumors

[Serrated polyps and their association with synchronous advanced colorectal neoplasia].

PubMed

Urman, Jesús; Gomez, Marta; Basterra, Marta; Mercado, María Del Rosario; Montes, Marta; Gómez Dorronsoro, Marisa; Garaigorta, Maitane; Fraile, María; Rubio, Eva; Aisa, Gregorio; Galbete, Arkaitz

2016-11-01

Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. A cross-sectional population-based study in all patients (1,538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analyzed. One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77-3.21] and OR: 2.29 [1.72-3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous ACN. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia.

PubMed

Deschner, E E; Ruperto, J; Wong, G; Newmark, H L

1991-07-01

Dietary quercetin (QU) and rutin (RU), phenolic flavonoids commonly found in many fruits and vegetables, were provided to CF1 female mice for 50 weeks to assess the ability of these compounds to inhibit azoxymethanol (AOM)-induced colonic neoplasia. In addition to a control group fed an AIN 76A diet, five other groups received that diet to which was added either 0.1, 0.5 or 2.0% QU and 1.0 or 4.0% RU. Acute studies revealed that, among saline controls, no alteration of any proliferative parameters of colonic epithelial cells was observed among those groups receiving any dose of QU or RU. However, among the AOM-treated mice, both 2% QU and 4% RU significantly reduced hyperproliferation and inhibited the shift of S-phase cells to the middle and upper portion of crypts. Moreover, mice fed these concentrations of QU and RU had significantly fewer AOM-induced focal areas of dysplasia (FADs) than those fed the control diet (0.2 +/- 0.4 and 0.4 +/- 0.5 versus 3.6 +/- 2.3 respectively). Tumors occurred more frequently in the distal half of the colon, regardless of treatment. Compared with controls, mice fed 2% QU had a significantly reduced tumor incidence (25.0% versus 5.9%, P = 0.03). Those fed 4% RU showed only a trend toward inhibition (25% versus 9.7%, P = 0.11). Nevertheless, both 2% QU and 4% RU suppressed tumor multiplicity, i.e. fewer tumors/animal arose in these groups than in the AOM-treated control mice (1.2 versus 2.3, P = 0.005; 1.1 versus 2.3, P = 0.003 respectively). Clearly, QU and RU exhibit significant activity in reducing AOM-induced hyperproliferation of colonic epithelial cells and FAD incidence. This behavior successfully forecast the ability of both flavonoids to suppress tumor multiplicity and ultimately tumor development.

Advanced proximal neoplasia of the colon in average-risk adults.

PubMed

Rabeneck, Linda; Paszat, Lawrence F; Hilsden, Robert J; McGregor, S Elizabeth; Hsieh, Eugene; M Tinmouth, Jill; Baxter, Nancy N; Saskin, Refik; Ruco, Arlinda; Stock, David

2014-10-01

Estimating risk for advanced proximal neoplasia (APN) based on distal colon findings can help identify asymptomatic persons who should undergo examination of the proximal colon after flexible sigmoidoscopy (FS) screening. We aimed to determine the risk of APN by most advanced distal finding among an average-risk screening population. Prospective, cross-sectional study. Teaching hospital and colorectal cancer screening center. A total of 4651 asymptomatic persons at average risk for colorectal cancer aged 50 to 74 years (54.4% women [n = 2529] with a mean [± standard deviation] age of 58.4 ± 6.2 years). All participants underwent a complete colonoscopy, including endoscopic removal of all polyps. We explored associations between several risk factors and APN. Logistic regression was used to identify independent predictors of APN. A total of 142 persons (3.1%) had APN, of whom 85 (1.8%) had isolated APN (with no distal findings). APN was associated with older age, a BMI >27 kg/m(2), smoking, distal advanced adenoma and/or cancer, and distal non-advanced tubular adenoma. Those with a distal advanced neoplasm were more than twice as likely to have APN compared with those without distal lesions. Distal findings used to estimate risk of APN were derived from colonoscopy rather than FS itself. In persons at average risk for colorectal cancer, the prevalence of isolated APN was low (1.8%). Use of distal findings to predict APN may not be the most effective strategy. However, incorporating factors such as age (>65 years), sex, BMI (>27 kg/m(2)), and smoking status, in addition to distal findings, should be considered for tailoring colonoscopy recommendations. Further evaluation of risk stratification approaches in other asymptomatic screening populations is warranted. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia.

PubMed

Gelaleti, Gabriela B; Granzotto, Adriana; Leonel, Camila; Jardim, Bruna V; Moschetta, Marina G; Carareto, Claudia M A; Zuccari, Debora Ap P C

2014-01-01

The genome of mammals is characterized by a large number of non-LTR retrotransposons, and among them, the CAN SINEs are characteristics of the canine species. Small amounts of DNA freely circulate in normal blood serum and high amounts are found in human patients with cancer, characterizing it as a candidate tumor-biomarker. The aim of this study was to estimate, through its absolute expression, the number of copies of CAN SINE sequences present in free circulating DNA of female dogs with mammary cancer, in order to correlate with the clinical and pathological characteristics and the follow-up period. The copy number of CAN SINE sequences was estimated by qPCR in 28 female dogs with mammary neoplasia. The univariate analysis showed an increased number of copies in female dogs with mammary tumor in female dogs >10 years old (p=0.02) and tumor time >18 months (p<0.05). The Kaplan-Meier test demonstrated a negative correlation between an increased number of copies and survival time (p=0.03). High amounts of CAN SINE fragments can be good markers for the detection of tumor DNA in blood and may characterize it as a marker of poor prognosis, being related to female dogs with shorter survival times. This estimate can be used as a prognostic marker in non-invasive breast cancer research and is useful in predicting tumor progression and patient monitoring.

One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice

PubMed Central

Aston-Mourney, Kathryn; Subramanian, Shoba L.; Zraika, Sakeneh; Samarasekera, Thanya; Meier, Daniel T.; Goldstein, Lynn C.

2013-01-01

The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated β-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing β-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and β-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, β-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced β-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates β-cell secretion without increasing amyloid formation and protects against amyloid-induced β-cell loss. This suggests a novel effect of sitagliptin to protect the β-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas. PMID:23736544

Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes.

PubMed

Romei, Cristina; Mariotti, Stefano; Fugazzola, Laura; Taccaliti, Augusto; Pacini, Furio; Opocher, Giuseppe; Mian, Caterina; Castellano, Maurizio; degli Uberti, Ettore; Ceccherini, Isabella; Cremonini, Nadia; Seregni, Ettore; Orlandi, Fabio; Ferolla, Piero; Puxeddu, Efisio; Giorgino, Francesco; Colao, Annamaria; Loli, Paola; Bondi, Fabio; Cosci, Barbara; Bottici, Valeria; Cappai, Antonello; Pinna, Giovanni; Persani, Luca; Verga, Uberta; Uberta, Verga; Boscaro, Marco; Castagna, Maria Grazia; Cappelli, Carlo; Zatelli, Maria Chiara; Faggiano, Antongiulio; Francia, Giuseppe; Brandi, Maria Luisa; Falchetti, Alberto; Pinchera, Aldo; Elisei, Rossella

2010-08-01

Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population. We collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres. The most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (P<0.0001). A statistically significant higher prevalence of mutations affecting non-cysteine codons was also found (P<0.0001). Furthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings.

An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.

PubMed

Reyes, M Carolina; Cooper, Kumarasen

2014-04-01

There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.

Galaxias australes con núcleo doble

NASA Astrophysics Data System (ADS)

Gimeno, G.; Díaz, R.; Carranza, G.

Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

Circulating Soluble Neuropilin-1 in Patients with Early Cervical Cancer and Cervical Intraepithelial Neoplasia Can Be Used as a Valuable Diagnostic Biomarker

PubMed Central

Yang, Shouhua; Cheng, Henghui; Huang, Zaiju; Wang, Xiaoling; Wan, Yinglu; Cai, Jing; Wang, Zehua

2015-01-01

Objective. To investigate soluble neuropilin-1 (sNRP-1) in circulating and NRP-1 protein in cervical tissues from patients with cervical cancer or cervical intraepithelial neoplasia (CIN). Methods. sNRP-1 was measured in 64 preoperative patients and 20 controls. NRP-1 protein in cervical tissue was detected in 56 patients and 20 controls. Results. Both sNRP-1 and NRP-1 proteins were correlated with stage. sNRP-1 presented a high diagnostic ability of cervical cancer and CIN, with a sensitivity of 70.97% and a specificity of 73.68%. Conclusions. sNRP-1 in circulating can serve as a possible valuable diagnostic biomarker for cervical cancer and CIN. PMID:25873749

Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2015-06-01

The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution.

PubMed

Phadnis, S V; Atilade, A; Bowring, J; Kyrgiou, M; Young, M P A; Evans, H; Paraskevaidis, E; Walker, P

2011-12-01

To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). Cohort study. A large tertiary teaching hospital in London. Women who underwent repeat excisional treatment for treatment failure or persistent CIN. Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex(®) database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. Differences in collagen expression were examined in the paired excisional treatment specimens. A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. There is no overall change in collagen distribution during regeneration following excisional treatment for CIN. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

[Research on sexually transmitted infections in asymptomatic heterosexual males whose partners have cervical intraepithelial neoplasia].

PubMed

Varela, José A; Otero, Luis; Junquera, Maria Luisa; Melón, Santiago; del Valle, Asunción; Vázquez, Fernando

2006-06-01

Human papillomaviruses (HPV) are the etiological agents of genital warts and of cervical intraepithelial neoplasia (CIN), and they are sexually transmitted. The aim of this study is to determine the prevalence of sexually transmitted infections (STI) in asymptomatic heterosexual males who consult their physicians seeking advice after their partners have been diagnosed with CIN. 181 asymptomatic males whose partners were women diagnosed with CIN were studied at the STI unit in Gijón over a five-year period (1999-2003). The same diagnostic protocol was used in all cases: clinical exam, genitoscopy and the taking of samples for bacterial, fungus and Trichomonas cultures, as well as samples for the genomic detection of Chlamydia, and syphilis, HIV and viral hepatitis serology. 101 infections were diagnosed in 85 patients (47 %). By order of greatest prevalence, these were: urethritis from Ureaplasma urealyticum (35/181; 19.3 %), genital warts (31/181; 17.1 %), Haemophilus spp. (12 de 181; 6.6 %) and mycotic balanoposthitis (10/181; 5.5 %). The prevalence of STI in the partners of women with CIN is high, and in these cases it is necessary to establish STI detection and control programs in both members of the couple.

Validation of a preclinical model of diethylnitrosamine-induced hepatic neoplasia in Yucatan miniature pigs

PubMed Central

Mitchell, Jennifer; Tinkey, Peggy T.; Avritscher, Rony; Van Pelt, Carolyn; Eskandari, Ghazaleh; George, Suraj Konnath; Xiao, Lianchun; Cressman, Erik; Morris, Jeffrey S.; Rashid, Asif; Kaseb, Ahmed O.; Amin, Hesham M.; Uthamanthil, Rajesh

2016-01-01

Objective The purpose of this study was to reduce time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n=2) or DEN (n=6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. Animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (~29 months). Results All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs, as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion To our knowledge, we are the first to demonstrate accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model. PMID:27305144

In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.

1994-10-01

Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Adverse Psychosexual Impact Related to the Treatment of Genital Warts and Cervical Intraepithelial Neoplasia

PubMed Central

Campaner, Adriana Bittencourt; Vespa Junior, Nelson; Giraldo, Paulo César; Leal Passos, Mauro Romero

2013-01-01

Objective. To compare the psychosexual impact related to the treatment of genital warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients presenting with HPV-induced genital lesions, belonging to one of two patient groups, were included in the study: 29 individuals with genital warts (GWs) and 46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of each woman were examined for extraction of data on the type of HPV-induced infection and treatment administered. Subjects were interviewed to collect sociodemographic data as well as personal, gynecologic, obstetric, and sexual history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F) questionnaire was applied to assess sexual function. After application of the questionnaire, patients answered specific questions produced by the researchers, aimed at assessing the impact of the disease and its treatment on their sexual lives. Results. It is noteworthy that patients with CIN 2/3 had statistically similar classification of sexual quotient to patients with GWs (P = 0.115). However, patients with GWs more frequently gave positive answers to the specific questions compared to patients with CIN 2/3. Conclusion. Based on these findings, it is clear that GWs have a greater impact on sexual behavior compared to CIN 2/3. PMID:26316956

A Risk Prediction Index for Advanced Colorectal Neoplasia at Screening Colonoscopy.

PubMed

Schroy, Paul C; Wong, John B; O'Brien, Michael J; Chen, Clara A; Griffith, John L

2015-07-01

Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer screening. Risk stratification for advanced colorectal neoplasia (ACN) might facilitate more effective shared decision making when selecting an appropriate screening option. Our objective was to develop and validate a clinical index for estimating the probability of ACN at screening colonoscopy. We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average-risk patients 50-79 years of age undergoing screening colonoscopy at two urban safety net hospitals. Predictors of ACN were identified using multiple logistic regression. Model performance was internally validated using bootstrapping methods. The final index consisted of five independent predictors of risk (age, smoking, alcohol intake, height, and a combined sex/race/ethnicity variable). Smoking was the strongest predictor (net reclassification improvement (NRI), 8.4%) and height the weakest (NRI, 1.5%). Using a simplified weighted scoring system based on 0.5 increments of the adjusted odds ratio, the risk of ACN ranged from 3.2% (95% confidence interval (CI), 2.6-3.9) for the low-risk group (score ≤2) to 8.6% (95% CI, 7.4-9.7) for the intermediate/high-risk group (score 3-11). The model had moderate to good overall discrimination (C-statistic, 0.69; 95% CI, 0.66-0.72) and good calibration (P=0.73-0.93). A simple 5-item risk index based on readily available clinical data accurately stratifies average-risk patients into low- and intermediate/high-risk categories for ACN at screening colonoscopy. Uptake into clinical practice could facilitate more effective shared decision-making for CRC screening, particularly in situations where patient and provider test preferences differ.

Risk of Human Papillomavirus (HPV) Infection and Cervical Neoplasia after Pregnancy.

PubMed

Trottier, Helen; Mayrand, Marie-Hélène; Baggio, Maria Luiza; Galan, Lenice; Ferenczy, Alex; Villa, Luisa L; Franco, Eduardo L

2015-10-07

Parity is well established as a risk factor for cervical cancer. It is not clear, however, how pregnancy influences the natural history of HPV infection and cervical neoplasia. Our objective was to study the risk of HPV infection and cervical squamous intraepithelial lesions (SIL) after pregnancy. We used the Ludwig-McGill cohort study which includes 2462 women recruited in Sao Paulo, Brazil in 1993-97 and followed for up to 10 years. Cellular specimens were collected every 4-6 months for Pap cytology and HPV detection and genotyping by a polymerase chain reaction protocol. Study nurses recorded pregnancy occurrence during follow-up. HPV and Pap results from pregnant women were available before and after, but not during pregnancy. The associations between pregnancy and post-partum HPV infection/SIL were studied using generalized estimating equation models with logistic link. Adjusted odds ratios (OR) were estimated with empirical adjustment for confounding. We recorded 122 women with a history of pregnancy during follow-up. Of these, 29 reintegrated the cohort study after delivery. No association between HPV and pregnancy was found. A single SIL case (high grade SIL) occurred post-partum. Likewise, there was no association between pregnancy and risk of low grade SIL or any-grade SIL at the next visit (adjusted OR = 0.84, 95 % CI: 0.46-15.33) after controlling for confounders. No associations were found between pregnancy and HPV or LSIL. The single observed case of HSIL post-partum was more than would be expected based on the rate of these abnormalities among non-pregnant women. As this association was found with only one case, caution is required in the interpretation of these results.

Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia.

PubMed

Tothova, Zuzana; Krill-Burger, John M; Popova, Katerina D; Landers, Catherine C; Sievers, Quinlan L; Yudovich, David; Belizaire, Roger; Aster, Jon C; Morgan, Elizabeth A; Tsherniak, Aviad; Ebert, Benjamin L

2017-10-05

Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34 + human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation. Employing these models to investigate therapeutic efficacy, we found that TET2 and cohesin-mutated hematopoietic cells were sensitive to azacitidine treatment. These findings demonstrate the potential for generating genetically defined models of human myeloid diseases, and they are suitable for examining the biological consequences of somatic mutations and the testing of therapeutic agents. Copyright © 2017 Elsevier Inc. All rights reserved.

[X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia: report of a family and literature review].

PubMed

He, T Y; Xia, Y; Li, C G; Li, C R; Qi, Z X; Yang, J

2018-01-02

Objective: To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'. He had suffered from recurrent upper respiratory tract infection and sinusitis previously. Hemoglobin level was 38 g/L. The absolute count of reticulocytes was 223.2×10(9)/L. Urobilinogen level was 38 μmol/L (3-16 μmol/L). Coomb's test was positive. Both total (77.2 μmol/L) and indirect bilirubin (66 μmol/L) levels were elevated. There was an inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger brother mainly suffered from recurrent upper respiratory tract infection, accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio and number of total B cells (45.7%). A total of 7 reports were retrieved including 11 male cases caused by MAGT1 gene mutation. These 11 cases were characterized by EBV viremia (11 cases), recurrent upper respiratory tract infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8 cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune thrombocytopenia or hemolytic anemia (2 cases). Conclusion: XMEN often manifests as male onset, recurrent upper respiratory tract infection, otitis media or sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune diseases and reduction of CD4(+)/CD8 (+)T cell

The Procurement of Non Developmental Items: Pros and Cons

DTIC Science & Technology

1994-09-01

commercial way of procurement will bring more advantages than disadvantages to DOD. The list of the pros greatly outweighs the cons . There is practically...AD-A285 009 MH PROCUREMENT OF NON DEVELOPMENTAL ITEMS: PROS AND CONS THES IS Giorgio Scappaticci. Lt. Col., Italian Air Force AFIT/GLMILALj94S-3 I...PROS AND CONS U;narmou,.ced 0 Justification THESIS Giorgio Scappaticci, Lt. Col., Italian Air Force Dist’ibution f Availability Codes AFIT/GLM/LAL

Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers.

PubMed

Yokoyama, Akira; Mizukami, Takeshi; Yokoyama, Tetsuji

2015-01-01

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV≥106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.

The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

PubMed

Burgos, J; Curran, A; Landolfi, S; Navarro, J; Tallada, N; Guelar, A; Crespo, M; Ocaña, I; Ribera, E; Falcó, V

2016-08-01

Electrocautery is one of the main treatment options for high-grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN. An observational study of HIV-infected men who have sex with men (MSM) who underwent screening for anal dysplasia was carried out. The on-treatment effectiveness of electrocautery was evaluated (according to biopsy findings measured 6-8 weeks after treatment) in patients with HGAIN. A complete response was defined as resolution of anal intraepithelial neoplasia (AIN), a partial response as regression to low-grade AIN and recurrence as biopsy-proven HGAIN during follow-up. From May 2009 to November 2014, 21.9% (126 of 576) of patients screened were found to have HGAIN. Electrocautery effectiveness was evaluated in 83 patients. A complete response was observed in 27 patients [32.5%; 95% confidence interval (CI) 23.4-53.2%], a partial response in 28 patients (33.7%; 95% CI 24.5-44.4%) and persistence in 28 patients (33.7%; 95% CI 24.5-44.4%). The patients with the most successful results (81.8%) required two to four sessions of electrocautery. After a mean follow-up of 12.1 months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9 months (95% CI 22-37.7 months). No patient progressed to invasive cancer during the study or developed serious adverse events after treatment. No factors associated with poor response or recurrences were observed. Although electrocautery is the standard treatment for anal dysplasia, almost 50% of patients with HGAIN in our study did not respond or relapsed. New treatment strategies are necessary to optimize the management of anal dysplasia. © 2015 British HIV Association.

Glycosylated hemoglobin concentrations in the blood of healthy dogs and dogs with naturally developing diabetes mellitus, pancreatic beta-cell neoplasia, hyperadrenocorticism, and anemia.

PubMed

Elliott, D A; Nelson, R W; Feldman, E C; Neal, L A

1997-09-15

To characterize glycosylated hemoglobin (GHb) concentrations in the blood of dogs with disorders that may affect serum glucose or blood GHb concentrations, and to determine whether changes in GHb concentration correlate with changes in control of diabetes in dogs. Prospective study. 63 healthy dogs, 9 dogs with anemia, 24 dogs with untreated hyperadrenocorticism, 12 dogs with pancreatic beta-cell neoplasia, 23 dogs with newly diagnosed diabetes mellitus, and 77 diabetic dogs treated with insulin. Control of diabetes in dogs treated with insulin was classified as good or poor on the basis of history, physical examination findings, changes in body weight, and measurement of serum glucose concentrations Sequential evaluations of control were performed and GHb concentration in blood was measured, by means of affinity chromatography, for 5 untreated diabetic dogs before and after initiating insulin treatment, for 10 poorly controlled diabetic dogs before and after increasing insulin dosage, and for 5 diabetic dogs before and after pancreatic islet cell transplantation. Mean (+/-SD) GHb concentration was 3.3 +/- 0.8% in the blood of healthy dogs. Compared with results from healthy dogs, mean GHb concentration was significantly lower in the blood of dogs with anemia and pancreatic beta-cell neoplasia and significantly higher in the blood of untreated diabetic dogs. Mean GHb concentration was significantly higher in the blood of 46 poorly controlled diabetic dogs, compared with 31 well-controlled diabetic dogs (7.3 +/- 1.8 vs 5.7 +/- 1.7%, respectively). Mean GHb concentration in blood decreased significantly in 5 untreated diabetic dogs after treatment (8.7 +/- 1.9 vs 5.3 +/- 1.9%). Mean GHb concentration in blood also decreased significantly in 10 poorly controlled diabetic dogs after control was improved and in 5 diabetic dogs after they had received a pancreatic islet cell transplant. Measurement of GHb concentration in blood may assist in monitoring control of

Clinical responses to focused ultrasound applied to women with vulval intraepithelial neoplasia.

PubMed

Jia, Ying; Wu, Jin; Xu, Man; Tang, Liangdan; Li, Chengzhi; Luo, Ming; Lou, Meng

2014-11-01

Focused ultrasound waves penetrate superficial tissues and are aimed toward the target tissues at specific depths to exert their biological effects. Focused ultrasound has been applied for a number of clinical indications, including vulval dystrophies and low-grade vulval disease. This study aimed to assess the efficacy and safety of focused ultrasound treatment of high-grade vulval intraepithelial neoplasia (VIN). Eighteen women with high-grade VIN were recruited and treated with focused ultrasound. During each posttreatment follow-up, the safety of, side effects of, and clinical responses to focused ultrasound were evaluated by a standardized protocol, including symptoms, clinical appearance, and histologic findings. All patients completed the designed follow-ups. In most cases, superficial mild to moderate swelling and blisters were seen in the focused ultrasound-treated skin but not in adjacent normal skin. Of the 18 patients, 16 showed complete histologic regression and resolution of symptoms 6 months after treatment. Of the other 2 patients, 1 showed complete regression after a second focused ultrasound treatment. The other patient did not respond to the focused ultrasound treatment and underwent a partial vulvectomy 6 months after treatment. None of the patients developed invasive carcinoma of the vulva during the follow-up period. One patient had local pruritus that was not alleviated by anti-inflammatory medication and local care. The complete responses observed in women with high-grade VIN treated by focused ultrasound, together with the preservation of adjacent normal tissue, suggest that focused ultrasound may be considered for treatment of high-grade VIN. © 2014 by the American Institute of Ultrasound in Medicine.

Prevalence and management of colorectal neoplasia in surgically treated esophageal cancer patients.

PubMed

Takeuchi, Daisuke; Koide, Naohiko; Komatsu, Daisuke; Suzuki, Akira; Miyagawa, Shinichi

2015-05-01

The existence of other primary tumors during the treatment of esophageal cancer patients has been an important issue. Our aim is to investigate the prevalence and management of colorectal neoplasia (CRN) in surgically treated esophageal cancer patients. Between 2002 and 2008, 93 patients with esophageal cancer were surgically treated. Seventy-three patients underwent subtotal esophagectomy and 20 underwent lower esophagectomy for esophageal cancer. Colonoscopy was available for detecting CRN before and after surgery. Eighty-nine (95.7%) of the 93 patients were screened by colonoscopy preoperatively or within a year from the operation. Thirty-nine patients (43.8%) with CRN were synchronously identified: adenoma in 34 (38.2%) and adenocarcinoma in 5 patients (5.6%). Eleven adenomas with high grade-dysplasia and 8 adenomas with low grade-dysplasia were removed endoscopically. Three superficial adenocarcinomas were endoscopically removed before surgery, and 2 adenocarcinomas were surgically removed. Seventy-four patients (83.1%) were followed using colonoscopy, and 11 subsequent CRN, including 2 superficial adenocarcinomas, were endoscopically detected in 8 patients (10.8%). The size of esophageal cancer was larger in the patients with than without CRN (p = 0.036). The body mass index in esophageal cancer patients with CRN tended to be higher than in those without CRN (p = 0.065). We noted that esophageal cancer is frequently associated with synchronous and/or metachronous colorectal cancer and adenomas. Colonoscopy is useful to detect and manage CRN before and after esophagectomy, although a few limitations exist. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

ConKit: a python interface to contact predictions.

PubMed

Simkovic, Felix; Thomas, Jens M H; Rigden, Daniel J

2017-07-15

Recent advances in protein residue contact prediction algorithms have led to the emergence of many new methods and a variety of file formats. We present ConKit , an open source, modular and extensible Python interface which allows facile conversion between formats and provides an interface to analyses of sequence alignments and sets of contact predictions. ConKit is available via the Python Package Index. The documentation can be found at http://www.conkit.org . ConKit is licensed under the BSD 3-Clause. hlfsimko@liverpool.ac.uk or drigden@liverpool.ac.uk. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.

PubMed

Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

2015-01-01

The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in

KRAS and GNAS Mutations in Pancreatic Juice Collected From the Duodenum of Patients at High Risk for Neoplasia Undergoing Endoscopic Ultrasound

PubMed Central

Eshleman, James R.; Norris, Alexis L.; Sadakari, Yoshihiko; Debeljak, Marija; Borges, Michael; Harrington, Colleen; Lin, Elaine; Brant, Aaron; Barkley, Thomas; Almario, J. Alejandro; Topazian, Mark; Farrell, James; Syngal, Sapna; Lee, Jeffrey H.; Yu, Jun; Hruban, Ralph H.; Kanda, Mitsuro; Canto, Marcia Irene; Goggins, Michael

2014-01-01

BACKGROUND & AIMS Pancreatic imaging can identify neoplastic cysts but not microscopic neoplasms. Mutation analysis of pancreatic fluid following secretin stimulation might identify microscopic neoplasias in the pancreatic duct system. We determined the prevalence of mutations in KRAS and GNAS genes in pancreatic juice from subjects undergoing endoscopic ultrasound for suspected pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms, or pancreatic adenocarcinoma. METHODS Secretin-stimulated juice samples were collected from the duodenum of 272 subjects enrolled in Cancer of the Pancreas Screening studies; 194 subjects were screened because of a family history of, or genetic predisposition to, pancreatic cancer and 78 were evaluated for pancreatic cancer (n=30) or other disorders (controls: pancreatic cysts, pancreatitis, or normal pancreata, n=48). Mutations were detected by digital high-resolution melt-curve analysis and pyrosequencing. The number of replicates containing a mutation determined the mutation score. RESULTS KRAS mutations were detected in pancreatic juice from larger percentages of subjects with pancreatic cancer (73%) or undergoing cancer screening (50%) than controls (19%) (P=.0005). A greater proportion of patients with pancreatic cancer had at least 1 KRAS mutation detected 3 or more times (47%) than screened subjects (21%) or controls (6%, P=.002). Among screened subjects, mutations in KRAS (but not GNAS) were found in similar percentages of patients with or without pancreatic cysts. However, a greater proportion of patients over 50 ys old had KRAS mutations (54.6%) than younger patients (36.3%) (P=.032); the older subjects also more mutations in KRAS (P=.02). CONCLUSIONS Mutations in KRAS are detected in pancreatic juice from the duodenum of 73% of patients with pancreatic cancer, and 50% of asymptomatic individuals with a high risk for pancreatic cancer. However, KRAS mutations are detected in pancreatic juice

ComSciCon: The Communicating Science Workshop for Graduate Students

NASA Astrophysics Data System (ADS)

Sanders, Nathan; Drout, Maria; Kohler, Susanna; Cook, Ben; ComSciCon Leadership Team

2018-01-01

ComSciCon (comscicon.com) is a national workshop series organized by graduate students, for graduate students, focused on leadership and training in science communication. Our goal is to empower young scientists to become leaders in their field, propagating appreciation and understanding of research results to broad and diverse audiences. ComSciCon attendees meet and interact with professional communicators, build lasting networks with graduate students in all fields of science and engineering from around the country, and write and publish original works. ComSciCon consists of both a flagship national conference series run annually for future leaders in science communication, and a series of regional and specialized workshops organized by ComSciCon alumni nationwide. We routinely receive over 1000 applications for 50 spots in our national workshop. Since its founding in 2012, over 300 STEM graduate students have participated in the national workshop, and 23 local spin-off workshops have been organized in 10 different locations throughout the country. This year, ComSciCon is working to grow as a self-sustaining organization by launching as an independent 501(c)(3) non-profit. In this poster we will discuss the ComSciCon program and methods, our results to date, potential future collaborations between ComSciCon and AAS, and how you can become involved.

CO2 laser total superficial vulvectomy: an outpatient treatment for wide multifocal vulvar intraepithelial neoplasia grade 3.

PubMed

Fallani, Maria Grazia; Fambrini, Massimiliano; Lozza, Virginia; Bianchi, Claudia; Pieralli, Annalisa

2012-01-01

The ideal treatment of large multifocal vulvar intraepithelial neoplasia grade 3 (VIN 3) in young patients is still debated. The goal is to prevent development of invasive vulvar cancer while preserving normal vulvar anatomy and function. The authors describe the case of a 37-year-old woman affected by a biopsy-proven VIN 3 involving the entire external genitalia. A total superficial vulvectomy was carried out in 2 closer sessions by CO(2) laser used in an excisional way. Both procedures were performed in an outpatient setting with the patient under local anesthesia and without suturing stitches or skin flaps. Definitive pathologic analysis confirmed VIN 3 with free margins. No intraoperative and postoperative complications were documented. Functional and anatomic outcomes were optimal, and no relapse occurred after 12 months of follow-up. Use of CO(2) laser total superficial vulvectomy shows promise of a safe and adequate treatment in selected young patients with VIN 3 involving the entire external genitalia. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

Trazando la materia oscura con cúmulos globulares

NASA Astrophysics Data System (ADS)

Forte, J. C.

Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo.

PubMed

Xu, Wenqin; Stadler, Cynthia K; Gorman, Kristen; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M; Pye, Geoffrey W; Eiden, Maribeth V

2013-07-09

Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype "KoRV-A," whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype "KoRV-B." KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population.

Evaluation of Inflammation Parameters in Philadelphia Negative Chronic Myeloproliferative Neoplasia Patients.

PubMed

Hacibekiroglu, Tuba; Akinci, Sema; Basturk, Abdulkadir; inal, Besime; Guney, Tekin; Bakanay, Sule Mine; Dilek, Imdat

2015-01-01

Chronic myeloproliferative diseases are clonal stem cell diseases which occur as a result of uncontrollable growth and reproduction of hematopoietic stem cells, which are the myeloid series source in bone marrow. Recent studies have suggested that chronic inflammation can be a triggering factor in the clonal change in chronic myeloproliferative neoplasia (CMPN). In our study, we evaluated the existence of a chronic inflammation process in our Philadelphia negative (Ph-)CMPN patients using inflammation parameters in combination with demographic, laboratory and clinical characteristics of the patients. Demographic characteristics, clinical and laboratorial data, and thrombosis histories of 99 Ph-CMPN patients, who were diagnosed at our outpatient clinic of hematology in accordance with WHO 2008 criteria, were analyzed retrospectively,with 80 healthy individuals of matching gender and age included as controls. Complete blood counts, sedimentation, C reactive protein (CRP), JAK V617F gene mutations, abdomen ultrasound images and previous thrombosis histories of these patients were retrospectively analyzed. Ph-CMPN and healthy control groups included 99 and 80 cases, respectively. PV, ET and MF diagnoses of patients were 43 (%43.4), 44 (44.4%) and 12 (12.1%), respectively. JAK V617F gene mutation was found to be positive in 64 (71.1%) of all cases and in 27(65.8%), 32 (82%), 5 (50%) of the cases in PV, ET and PMF groups, respectively. Thrombosis was determined as 12 (12%) in the entire group, 12.5% in the JAK V617F negative and 15.3% in the positive patients, with no statistical significance (p=0.758). No significant difference was observed between patients with and without previous thrombosis history in respect to hemogram parameters, sedimentation and CRP (p>0.05), neutrophil to lymphocyte ratio (NLR), erythrocyte distribution width (RDW), mean platelet volume (MPV) and sedimentation levels of the patient.

Prostitution, HIV, and cervical neoplasia: a survey in Spain and Colombia.

PubMed

de Sanjosé, S; Palacio, V; Tafur, L; Vazquez, S; Espitia, V; Vazquez, F; Roman, G; Muñoz, N; Bosch, F X

1993-01-01

The prevalence of cervical intraepithelial neoplasia (CIN) and the association of CIN with prostitution was examined in Oviedo, a region in Spain with low incidence of cervical cancer, and in Cali, Colombia, where the incidence of cervical cancer is 6-10 times higher. In Oviedo, the study included 758 prostitutes attending a sexually transmitted diseases clinic and 1203 nonprostitutes attending a family-planning clinic. In Cali, 775 prostitutes and 1795 nonprostitutes attending health centers were included. Seropositivity to common sexually transmitted agents was investigated in Spanish prostitutes. No significant difference was found in the prevalence of CIN between Oviedo and Cali in both prostitutes (2.5 versus 1.8%) and nonprostitutes (1.2 versus 1.1%). Prostitutes had a 2-fold increased risk of CIN as compared to nonprostitutes; in Spain, the prevalence odds ratio (POR) was 2.3 and the 95% confidence interval (CI) was 1.1-4.5, and, in Colombia, POR was 1.8 and the 95% CI was 0.9-3.5. Among prostitutes in Oviedo, human immunodeficiency virus (HIV) prevalence was 4.9% and HIV-positive prostitutes showed a high risk of CIN as compared to HIV-negative prostitutes (POR, 12.7; 95% CI, 3.9-40.9); 76% of HIV-positive prostitutes were i.v. drug users and showed an increased seroprevalence of other sexually transmitted diseases. HIV-negative prostitutes did not show any increased risk of CIN (POR, 1.2; 95% CI, 0.5-2.8). These results show that among nonprostitutes the prevalence of CIN was not statistically different between the two cities in Spain and Colombia; prostitutes were at moderate increased risk compared to nonprostitutes in both cities.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein Supplements: Pros and Cons.

PubMed

Samal, Jay Rabindra Kumar; Samal, Indira R

2018-05-04

To provide a comprehensive analysis of the literature examining the pros and cons of protein supplementation, various articles on protein supplementation were obtained from Google Scholar, PubMed, and National Center for Biotechnology Information. Over the past few years, protein supplementation has become commonplace for gym-goers as well as for the public. A large segment of the general population relies on protein supplementation for meal replacement, weight reduction, and purported health benefits. These protein supplements have varying pros and cons associated with them, which are often overlooked by the public. This review aims to assimilate existing studies and form a consensus regarding the benefits and disadvantages of protein supplementation. The purported health benefits of protein supplementation have led to overuse by both adults and adolescents. Although the pros and cons of protein supplementation is a widely debated topic, not many studies have been conducted regarding the same. The few studies that exist either provide insufficient evidence or have not employed proper conditions for the conduct of the tests. It should be considered that protein supplements are processed materials and often do not contain other essential nutrients required for the sustenance of a healthy lifestyle. It is suggested that the required protein intake should be obtained from natural food sources and protein supplementation should be resorted to only if sufficient protein is not available in the normal diet.

ConSpeciFix: Classifying prokaryotic species based on gene flow.

PubMed

Bobay, Louis-Marie; Ellis, Brian Shin-Hua; Ochman, Howard

2018-05-16

Classification of prokaryotic species is usually based on sequence similarity thresholds, which are easy to apply but lack a biologically-relevant foundation. Here, we present ConSpeciFix, a program that classifies prokaryotes into species using criteria set forth by the Biological Species Concept, thereby unifying species definition in all domains of life. ConSpeciFix's webserver is freely available at www.conspecifix.com. The local version of the program can be freely downloaded from https://github.com/Bobay-Ochman/ConSpeciFix. ConSpeciFix is written in Python 2.7 and requires the following dependencies: Usearch, MCL, MAFFT and RAxML. ljbobay@uncg.edu.

Ocular surface squamous neoplasia in HIV-infected patients: current perspectives.

PubMed

Rathi, Shweta Gupta; Ganguly Kapoor, Anasua; Kaliki, Swathi

2018-01-01

Ocular surface squamous neoplasia (OSSN) refers to a spectrum of conjunctival and corneal epithelial tumors including dysplasia, carcinoma in situ, and invasive carcinoma. In this article, we discuss the current perspectives of OSSN associated with HIV infection, focusing mainly on the epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of these tumors in patients with HIV. Upsurge in the incidence of OSSN with the HIV pandemic most severely affected sub-Saharan Africa, due to associated risk factors, such as human papilloma virus and solar ultraviolet exposure. OSSN has been reported as the first presenting sign of HIV/AIDS in 26%-86% cases, and seropositivity is noted in 38%-92% OSSN patients. Mean age at presentation of OSSN has dropped to the third to fourth decade in HIV-positive patients in developing countries. HIV-infected patients reveal large aggressive tumors, higher-grade malignancy, higher incidence of corneal, scleral, and orbital invasion, advanced-stage T4 tumors, higher need for extended enucleation/exenteration, and increased risk of tumor recurrence. Current management of OSSN in HIV-positive individuals is based on standard treatment guidelines described for OSSN in the general population, as there is little information available about various treatment modalities or their outcomes in patients with HIV. OSSN can occur at any time in the disease course of HIV/AIDS, and no significant trend has been discovered between CD4 count and grade of OSSN. Furthermore, the effect of highly active antiretroviral therapy on OSSN is controversial. The current recommendation is to conduct HIV screening in all cases presenting with OSSN to rule out undiagnosed HIV infection. Patient counseling is crucial, with emphasis on regular follow-up to address high recurrence rates and early presentation to an ophthalmologist for of any symptoms in the unaffected eye. Effective evidence-based interventions are needed to allow early diagnosis

Vulvar intraepithelial neoplasia with superficially invasive carcinoma of the vulva.

PubMed

Herod, J J; Shafi, M I; Rollason, T P; Jordan, J A; Luesley, D M

1996-05-01

To investigate the long-term outcome of patients presenting with vulvar intraepithelial neoplasia (VIN) with superficially invasive carcinoma of the vulva (SICa). A retrospective study using information obtained from patient case notes. Twenty-six women found at presentation to have VIN in association with superficially invasive carcinoma were identified during a 15-year period. Pruritus vulvae was the most frequent presenting symptom in 18 patients (69%). Sixteen women (61.5%) had multiple symptoms. Features noted at vulvar examination were variable and none were pathognomonic of either VIN or of superficial invasion. All patients had VIN 3 in association with a superficially invasive carcinoma. Histological changes associated with human papillomavirus were found in 19 (73%) women. Half had a co-existent or previous abnormality of the lower genital tract. Local excision was the most frequent initial treatment (n = 9 [35%]). Mean follow up time was 65 months (range 12-174). Disease persisted after primary treatment in five women (19%). Both histological recurrence (of either VIN or SICa) or symptomatic recurrence occurred in 10 patients (38%). All patients who experienced recurrence did so within 36 months of treatment. Overall, 12 patients (46%) relapsed (histological or symptomatic recurrence); the mean time was 18 months. Fourteen patients (54%) were managed satisfactorily by their initial treatment. One patient died of recurrent cervical cancer. Three progressed to frankly invasive disease: two (aged 31 and 39 years) with carcinoma of the vulva and one aged 34 years with carcinoma of the perianal margin. All are alive and well after treatment. One patient had recurrence of superficially invasive carcinoma treated by local excision with no further problems. No episode of metastasis via lymphatic or vascular channels has been seen. Patients with superficially invasive carcinoma of the vulva may be safely treated by local excisional methods without recourse to

Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia

NASA Astrophysics Data System (ADS)

Schwarz, Richard Alan

Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue

Surveillance colonoscopy after endoscopic treatment for colorectal neoplasia: From the standpoint of the Asia-Pacific region.

PubMed

Matsuda, Takahisa; Chiu, Han-Mo; Sano, Yasushi; Fujii, Takahiro; Ono, Akiko; Saito, Yutaka

2016-04-01

Colonoscopy is considered the gold standard to detect and remove colorectal neoplasia. The efficacy of colonoscopy with polypectomy to reduce colorectal cancer incidence and mortality has been demonstrated. Recently, post-polypectomy surveillance colonoscopy has become a necessary intervention in daily practice not only in Western countries but also in the Asia-Pacific region. Therefore, it is crucial to establish new clinical practice guidelines to reduce the number of unnecessary surveillance colonoscopies in order to create space for screening colonoscopy. The Asia-Pacific Consensus group recommended that surveillance colonoscopy interval should be tailored according to risk level of index colonoscopy. However, precise guidelines on interval of surveillance cannot be given because of a lack of prospective data. According to Korean and Australian guidelines, surveillance intervals after index colonoscopy of 5 years for low-risk subjects and 3 years for high-risk subjects are recommended in Asia-Pacific regions at present. Prospective data including long-term outcomes from the Japan Polyp Study, which is a multicenter randomized control trial, would be useful to establish the Asia-Pacific consensus in the near future. © 2016 Japan Gastroenterological Endoscopy Society.

Concordance of gross surgical and final fixed margins in vulvar intraepithelial neoplasia 3 and vulvar cancer.

PubMed

DeSimone, Christopher P; Crisp, Meredith P; Ueland, Frederick R; DePriest, Paul D; van Nagell, John R; Lele, Subodh M; Modesitt, Susan C

2006-08-01

To prospectively evaluate the concordance of initial surgical vulvar margins and final fixed margins and to determine the amount of microscopic pathology of grossly negative margins in women with vulvar intraepithelial neoplasia (VIN) 3 or vulvar carcinoma. Women with VIN 3 or vulvar carcinoma undergoing surgical excision were identified. Prior to excision, acetic acid was used to highlight the lesions, and 2 sutures were placed, 1 at the edge of gross disease and another 1 cm distal from the first. After specimen removal and fixation, the distance between sutures and microscopic involvement of VIN was determined. Twenty-seven women were enrolled; however, only 19 had final fixed specimens that could be accurately measured. The median fixed distance of the vulvar margin was 0.85 cm (mean, 0.83; SD, 0.19) as compared to the gross, 1-cm margin (p = 0.001). Three subjects (16%) had microscopic involvement by VIN 3 in the grossly negative epithelium between the 2 sutures, but none had a positive peripheral margin. The gross surgical margin after vulvar resection is reduced by 15% when measured in its final fixed state, and a grossly negative 1-cm margin will seldom harbor significant disease.

The histologic features of intratubular germ cell neoplasia and its correlation with tumor behavior.

PubMed

Basiri, Abbas; Movahhed, Saeed; Parvin, Mahmood; Salimi, Maziar; Rezaeetalab, Gholam Hossein

2016-05-01

To assess the prevalence of intratubular germ cell neoplasia (ITGCN) in patients with concurrent testis tumor and its correlation with histologic features and serum tumor markers. From 2003 to 2015, 179 patients underwent radical orchiectomy due to testicular mass. Tissue specimens were evaluated by an expert uro-pathologist using immunohistochemistry (IHC) staining, in addition to light microscopy, to identify presence of ITGCN. Patients' demographic characteristics, histologic subtypes, pathologic stage of tumor and serum tumor markers were gathered and analyzed. Eighty-five out of 179 patients (47.5%) had concomitant ITGCN according to IHC staining. There was not statistically significant difference in histologic type, histologic components, cryptorchidism, and lymphovascular invasion between the 2 groups (p=0.151, p=0.11, p=0.233, p=0.413, and p=0.14, respectively). The prevalence of ITGCN was significantly higher in patients with stage T2 and T3 of tumor than those with stage T1. Elevated serum alpha feto protein level is much common in patients with ITGCN (p<0.001). The prevalence of concurrent ITGCN in our region is lower than previous data from western countries. ITGCN is more common in higher tumor stages and is accompanied with elevated serum alpha feto protein levels before surgery. Presence of ITGCN in adjacent tissue may suggest a negative cancer behavior.

Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA

NASA Astrophysics Data System (ADS)

Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

1989-06-01

Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

A Retrospective Study of the Prevalence and Classification of Intestinal Neoplasia in Zebrafish (Danio Rerio)

PubMed Central

Paquette, Colleen E.; Buchner, Cari; Tanguay, Robert L.; Guillemin, Karen; Mason, Timothy J.; Peterson, Tracy S.

2013-01-01

Abstract For over a decade, spontaneous intestinal neoplasia has been observed in zebrafish (Danio rerio) submitted to the ZIRC (Zebrafish International Resource Center) diagnostic service. In addition, zebrafish displayed preneoplastic intestinal changes including hyperplasia, dysplasia, and enteritis. A total of 195 zebrafish, representing 2% of the total fish submitted to the service, were diagnosed with these lesions. Neoplastic changes were classified either as adenocarcinoma or small cell carcinoma, with a few exceptions (carcinoma not otherwise specified, tubular adenoma, and tubulovillous adenoma). Tumor prevalence appeared similarly distributed between sexes and generally occurred in zebrafish greater than 1 year of age, although neoplastic changes were observed in fish 6 months of age. Eleven lines displayed these preneoplastic and neoplastic changes, including wild-types and mutants. Affected zebrafish originated from 18 facilities, but the majority of fish were from a single zebrafish research facility (hereafter referred to as the primary facility) that has submitted numerous samples to the ZIRC diagnostic service. Zebrafish from the primary facility submitted as normal sentinel fish demonstrate that these lesions are most often subclinical. Fish fed the diet from the primary facility and held at another location did not develop intestinal lesions, indicating that diet is not the etiologic agent. PMID:23544991

Increased incidence of cervical intraepithelial neoplasia in young women in the Mitte district, Berlin, Germany.

PubMed

Blohmer, J U; Schmalisch, G; Klette, I; Grineisen, Y; Kohls, A; Guski, H; Lichtenegger, W

1999-01-01

To investigate whether the incidence of cervical intraepithelial neoplasia (CIN), in particular of high grade CIN, increased in Berlin during the period 1970-1989 and whether the ages of women with CIN had decreased. In the former German Democratic Republic, which had a highly centralized public health system, all gynecologic operations performed on women living in the Mitte district of Berlin were carried out during the period 1970-1989 (when the Berlin Wall fell) in the gynecologic clinic of the Charité Hospital. The incidence of all CIN increased from year to year over the observation period: 0.04% (1970-1971), 0.10% (1980-1981), 0.39% (1988-1989). There was a particularly high increase in the incidence of high grade intraepithelial neoplasms (CIN 3): 0.016% (1970-1971), 0.056% (1980-1981), 0.25% (1988-1989). With a virtually unchanged age distribution for women in the Mitte district of Berlin, the median age of women with CIN 3 decreased significantly from 1970 to 1989, from 39.5 (1970) to 33 (1989) (P < .001). The increase in the incidence of CIN, especially of high grade CIN, as well as the reduction in age for onset of the disease, makes high participation in screening necessary, above all among young women.

HR-HPV E6/E7 mRNA In Situ Hybridization: Validation Against PCR, DNA In Situ Hybridization, and p16 Immunohistochemistry in 102 Samples of Cervical, Vulvar, Anal, and Head and Neck Neoplasia.

PubMed

Mills, Anne M; Dirks, Dawn C; Poulter, Melinda D; Mills, Stacey E; Stoler, Mark H

2017-05-01

Dysregulated expression of oncogenic types of E6 and E7 is necessary for human papillomavirus (HPV)-driven carcinogenesis. An HPV E6/E7 mRNA in situ hybridization (ISH) assay covering 18 common high-risk types ("HR-RISH," aka HR-HPV RNA18 ISH) has not been extensively studied in the anogenital tract or validated on automated technology. We herein compare HR-RISH to DNA polymerase chain reaction (PCR), p16 immunohistochemistry, and a previously available HPV DNA ISH assay in HPV-related anogenital and head and neck (H&N) neoplasia. A total of 102 squamous intraepithelial lesions (16 CIN1, 25 CIN3, 3 AIN1, 12 AIN3, 9 VIN3)/invasive squamous cell carcinomas (17 cervical, 2 anal, 18 H&N) as well as 10 normal and 15 reactive cervix samples were collected. HR-RISH, DNA ISH, and p16 immunohistochemistry were performed on whole formalin-fixed, paraffin-embedded sections. RNA ISH for 6 low-risk HPV types (LR-RISH) was also performed. RNA and DNA ISH assays used automated systems. HR-HPV PCR was performed on morphology-directed formalin-fixed, paraffin-embedded punches. HR-RISH was ≥97% sensitive for PCR+ and p16+ neoplasia, as well as morphologically defined anogenital high grade squamous intraepithelial lesion/invasive squamous cell carcinoma. HR-RISH was also positive in 78% of anogenital low grade squamous intraepithelial lesion, including 81% of CIN1. Furthermore, a subset of PCR-negative/invalid and p16-negative lesions was positive for HR-RISH. Only 1 problematic reactive cervix sample and no normal cervix samples stained. These results demonstrate that HR-RISH is a robust method for the detection of HR-HPV-related neoplasia and provides insight into HPV pathobiology. Performance meets or exceeds that of existing assays in anogenital and H&N lesions and may play a role in resolving diagnostically challenging CIN1 versus reactive cases.

Games Con Men Play: The Semiosis of Deceptive Interaction.

ERIC Educational Resources Information Center

Hankiss, Agnes

1980-01-01

Analyzes some of the most frequent deceptive interactions as rendered through case histories of male con artists and their victims taken from police records. Discusses the recurrent elements in both the con-games strategies and victims' way of interpreting those strategies. (JMF)

Can the FIGO 2000 scoring system for gestational trophoblastic neoplasia be simplified? A new retrospective analysis from a nationwide dataset.

PubMed

Eysbouts, Y K; Ottevanger, P B; Massuger, L F A G; IntHout, J; Short, D; Harvey, R; Kaur, B; Sebire, N J; Sarwar, N; Sweep, F C G J; Seckl, M J

2017-08-01

Worldwide introduction of the International Fedaration of Gynaecology and Obstetrics (FIGO) 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible. Between January 2003 and December 2012, 813 patients diagnosed with gestational trophoblastic neoplasia were identified at the Trophoblastic Disease Centre in London and scored using the FIGO 2000. Multivariable analysis and stepwise logistic regression were carried out to evaluate whether the FIGO 2000 scoring system could be simplified. Of the eight FIGO risk factors only pre-treatment serum human chorionic gonadotropin (hCG) levels exceeding 10 000 IU/l (OR = 5.0; 95% CI 2.5-10.4) and 100 000 IU/l (OR = 14.3; 95% CI 4.7-44.1), interval exceeding 7 months since antecedent pregnancy (OR = 4.1; 95% CI 1.0-16.2), and tumor size of over 5 cm (OR = 2.2; 95% CI 1.3-3.6) were identified as independently predictive for single-agent resistance. In addition, increased risk was apparent for antecedent term pregnancy (OR = 3.4; 95% CI 0.9-12.7) and the presence of five or more metastases (OR = 3.5; 95% CI 0.4-30.4), but patient numbers in these categories were relatively small. Stepwise logistic regression identified a simplified risk scoring model comprising age, pretreatment serum hCG, number of metastases, antecedent pregnancy, and interval but omitting tumor size, previous failed chemotherapy, and site of metastases. With this model only 1 out 725 patients was classified different from the FIGO 2000 system. Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi

Clonal evolution in paired endometrial intraepithelial neoplasia/atypical hyperplasia and endometrioid adenocarcinoma.

PubMed

Russo, Mariano; Broach, James; Sheldon, Kathryn; Houser, Kenneth R; Liu, Dajiang J; Kesterson, Joshua; Phaeton, Rebecca; Hossler, Carrie; Hempel, Nadine; Baker, Maria; Newell, Jordan M; Zaino, Richard; Warrick, Joshua I

2017-09-01

Endometrial intraepithelial neoplasia (EIN) and atypical endometrial hyperplasia (AH) are histomorphologically defined precursors to endometrioid adenocarcinoma, which are unified as EIN/AH by the World Health Organization. EIN/AH harbors a constellation of molecular alterations similar to those found in endometrioid adenocarcinoma. However, the process of clonal evolution from EIN/AH to carcinoma is poorly characterized. To investigate, we performed next-generation sequencing, copy number alteration (CNA) analysis, and immunohistochemistry for mismatch repair protein expression on EIN/AH and endometrioid adenocarcinoma samples from 6 hysterectomy cases with spatially distinct EIN/AH and carcinoma. In evaluating all samples, EIN/AH and carcinoma did not differ in mutational burden, CNA burden, or specific genes mutated (all P>.1). All paired EIN/AH and carcinoma samples shared at least one identical somatic mutation, frequently in PI(3)K pathway members. Large CNAs (>10 genes in length) were identified in 83% of cases; paired EIN/AH and carcinoma samples shared at least one identical CNA in these cases. Mismatch repair protein expression matched in all paired EIN/AH and carcinoma samples. All paired EIN/AH and carcinoma samples had identical The Cancer Genome Atlas subtype, with 3 classified as "copy number low endometrioid" and 3 classified as "microsatellite instability hypermutated." Although paired EIN/AH and carcinoma samples were clonal, private mutations (ie, present in only one sample) were identified in EIN/AH and carcinoma in all cases, frequently in established cancer-driving genes. These findings indicate that EIN/AH gives rise to endometrioid adenocarcinoma by a complex process of subclone evolution, not a linear accumulation of molecular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrated expression analysis identifies transcription networks in mouse and human gastric neoplasia.

PubMed

Chen, Zheng; Soutto, Mohammed; Rahman, Bushra; Fazili, Muhammad W; Peng, DunFa; Blanca Piazuelo, Maria; Chen, Heidi; Kay Washington, M; Shyr, Yu; El-Rifai, Wael

2017-07-01

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach [Tff1-KO (LGD) and Tff1 wild-type (normal)] and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P < .05). Using Ingenuity pathway analysis, these genes mapped to important transcription networks that include MYC, STAT3, β-catenin, RELA, NFATC2, HIF1A, and ETS1 in both human and mouse. Further analysis demonstrated activation of FOXM1 and inhibition of TP53 transcription networks in human gastric cancers but not in Tff1-KO LGD lesions. Using real-time RT-PCR, we validated the deregulated expression of several genes (VCAM1, BGN, CLDN2, COL1A1, COL1A2, COL3A1, EpCAM, IFITM1, MMP9, MMP12, MMP14, PDGFRB, PLAU, and TIMP1) that map to altered transcription networks in both mouse and human gastric neoplasia. Our study demonstrates significant similarities in deregulated transcription networks in human gastric cancer and gastric tumorigenesis in the Tff1-KO mouse model. The data also suggest that activation of MYC, STAT3, RELA, and β-catenin transcription networks could be an early molecular step in gastric carcinogenesis. © 2017 Wiley Periodicals, Inc.

Breath Analysis Science at PittCon 2012, Orlando, Florida

EPA Science Inventory

Breath analysis science was featured in three organized sessions at this year’s Pittsburgh Conference and Exposition, or ‘PittCon 2012’ (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

Medical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported

The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.

PubMed

Hanks, Joanna; Ayed, Iyeman; Kukreja, Neil; Rogers, Chris; Harris, Jessica; Gheorghiu, Alina; Liu, Chee Ling; Emery, Peter; Pufulete, Maria

2013-12-01

Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation. We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon. We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively. Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001). MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.

Parenchymal signal intensity in 3-T body MRI of dogs with hematopoietic neoplasia.

PubMed

Feeney, Daniel A; Sharkey, Leslie C; Steward, Susan M; Bahr, Katherine L; Henson, Michael S; Ito, Daisuke; O'Brien, Timothy D; Jessen, Carl R; Husbands, Brian D; Borgatti, Antonella; Modiano, Jaime F

2013-04-01

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well.

Parenchymal Signal Intensity in 3-T Body MRI of Dogs with Hematopoietic Neoplasia

PubMed Central

Feeney, Daniel A; Sharkey, Leslie C; Steward, Susan M; Bahr, Katherine L; Henson, Michael S; Ito, Daisuke; O'Brien, Timothy D; Jessen, Carl R; Husbands, Brian D; Borgatti, Antonella; Modiano, Jaime F

2013-01-01

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well. PMID:23582424

Genetic mapping and predictive testing for multiple endocrine neoplasia type 1 (MEN1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pandit, S.D.; Read, C.; Liu, L.

1994-09-01

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with an estimated prevalance of 20-200 per million persons. It is characterized by the combined occurence of tumors involving two or more endocrine glands, namely the parathyroid glands, the endocrine pancreas and the anterior pituitary. This disorder affects virtually all age groups with an average range of 20-60 years. Linkage analysis mapped the MEN1 locus to 11q13 near the human muscle glycogen phosphorylase (PYGM) locus. Additional genetic mapping and deletion analysis studies have refined the region containing the MEN1 locus to a 3 cM interval flanked by markers PYGMmore » and D11S146/D11S97, a physical distance of approximately 1.5 Mb. We have identified 8 large families segregating MEN1 (71 affected from a population of 389 individuals). A high resolution reference map for the 11q13 region has been constructed using four new microsatellite markers, the CEPH reference (40 family) pedigree resource, and the CRI-MAP program package. Subsequent analyses using the LINKAGE program package and 8 MEN 1 families placed the MEN1 locus within the context of the microsatellite map. This map was used to develop a linkage-based predictive test. These markers have also been used to further refine the interval containing the MEN1 locus from the study of chromosome deletions (loss of heterozygosity, LOH studies) in paired sets of tumor and germline DNA from 87 MEN 1 affected individuals.« less

ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

PubMed

Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

2009-06-01

To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

Interleukin-10 gene -1082 G/A polymorphism in cervical cancer and cervical intraepithelial neoplasia: meta-analysis.

PubMed

Zhang, Shuo; Kong, Ya-Lin; Li, Ya-Li; Yin, Yan-Wei

2014-12-01

To assess the association between polymorphism in the interleukin (IL)-10 promoter region of 1082 G/A and the risk of cervical cancer and/or cervical intraepithelial neoplasia (CIN), using meta-analysis. The electronic literature databases PubMed®, Embase®, Web of Science, CBMdisc and CNKI were searched for relevant studies. The strength of association between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN was measured using pooled odds ratios with 95% confidence intervals in four genetic models: allelic model (A allele versus G allele); additive model (A/A versus G/G); recessive model (A/A versus G/A+G/G); dominant model (A/A+G/A versus G/G). Eight studies involving 1983 cases and 1618 controls were identified and included in the meta-analysis. No significant associations were found between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN in any of the genetic models. IL-10 gene -1082 G/A polymorphism does not appear to be associated with the risk of cervical cancer and/or CIN. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Proteinase-activated receptor 2 (PAR-2) in gastrointestinal and pancreatic pathophysiology, inflammation and neoplasia.

PubMed

Søreide, Kjetil

2008-08-01

Of all the body systems, the gastrointestinal (GI) tract is the most exposed to proteinases. Proteolytic activity must thus be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological GI conditions. The protease-activated receptor-2 (PAR-2) is expressed in numerous cell types within the GI tract, suggesting both multiple functions and numerous modes of receptor activation. Although best known as a pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers. Of interest, trypsin and PAR-2 act together in an autocrine loop that promotes proliferation, invasion and metastasis in neoplasia through various mechanisms. Trypsin and PAR-2 seem to act both directly and indirectly through activation of other proteinase cascades, including metalloproteinases. PAR-2 activation can participate in inflammatory reactions, be protective to mucosal surfaces, send or inhibit nociceptive messages, modify gut motility or secretory functions, and stimulate cell proliferation and motility. Several studies point to a role for the PARs in disease processes of the GI tract and pancreas ranging from inflammatory bowel disease, symptoms associated with irritable bowel syndrome, pain in pancreatitis, development of colon and other GI cancers, and even infectious colitis. Proteinases should not only be considered from the traditional view as digestive or degradative enzymes in the gut, but additionally as signalling molecules that actively participate in the spectrum of physiology and diseased states of the GI tract.

Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia.

PubMed

Chakrabarty, Sanjiban; Varghese, Vinay Koshy; Sahu, Pranoy; Jayaram, Pradyumna; Shivakumar, Bhadravathi M; Pai, Cannanore Ganesh; Satyamoorthy, Kapaettu

2017-06-27

Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia. Findings from the study are also compared with previously published genome wide and exome sequencing data in inflammatory bowel disease-associated and sporadic colorectal carcinoma. Next-generation sequencing analysis identified 1107 mutations in 275 genes in UCHR subjects. In addition to TP53 (17%) and KRAS (22%) mutations, recurrent mutations in APC (33%), ACVR2A (61%), ARID1A (44%), RAF1 (39%) and MTOR (61%) were observed in UCHR subjects. In addition, APC, FGFR3, FGFR2 and PIK3CA driver mutations were identified in UCHR subjects. Recurrent mutations in ARID1A (44%), SMARCA4 (17%), MLL2 (44%), MLL3 (67%), SETD2 (17%) and TET2 (50%) genes involved in histone modification and chromatin remodelling were identified in UCHR subjects. Our study identifies new oncogenic driver mutations which may be involved in the transition of non-dysplastic cells to dysplastic phenotype in the subjects with long-standing UC with high risk of progression into colorectal neoplasia.

The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

PubMed

Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

2016-08-01

Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice. Copyright © 2016 Norwegian Institute of Public Health. Published by Elsevier Ltd.. All rights reserved.

An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

PubMed

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

PubMed Central

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

In vivo white light and contrast-enhanced vital-dye fluorescence imaging of Barrett's-related neoplasia in a single-endoscopic insertion

NASA Astrophysics Data System (ADS)

Tang, Yubo; Carns, Jennifer; Polydorides, Alexandros D.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

2016-08-01

A modular video endoscope is developed to enable both white light imaging (WLI) and vital-dye fluorescence imaging (VFI) in a single-endoscopic insertion for the early detection of cancer in Barrett's esophagus (BE). We demonstrate that VFI can be achieved in conjunction with white light endoscopy, where appropriate white balance is used to correct for the presence of the emission filter. In VFI mode, a contrast enhancement feature is implemented in real time to further highlight glandular patterns in BE and related malignancies without introducing artifacts. In a pilot study, we demonstrate accurate correlation of images in two widefield modalities, with representative images showing the disruption and effacement of glandular architecture associated with cancer development in BE. VFI images of these alterations exhibit enhanced contrast when compared to WLI. Results suggest that the usefulness of VFI in the detection of BE-related neoplasia should be further evaluated in future in vivo studies.

Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

2016-03-01

Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice

PubMed Central

M., Soffritti; M., Padovani; E., Tibaldi; L., Falcioni; F., Manservisi; M., Lauriola; L., Bua; M., Manservigi; F., Belpoggi

2016-01-01

Background Sucralose is an organochlorine artificial sweetener approximately 600 times sweeter than sucrose and used in over 4,500 products. Long-term carcinogenicity bioassays on rats and mice conducted on behalf of the manufacturer have failed to show the evidence of carcinogenic effects. Objective The aim of this study was to evaluate the carcinogenic effect of sucralose in mice, using a sensitive experimental design. Methods Five groups of male (total n = 457) and five groups female (total n = 396) Swiss mice were treated from 12 days of gestation through the lifespan with sucralose in their feed at concentrations of 0, 500, 2,000, 8,000, and 16,000 ppm. Results We found a significant dose-related increased incidence of males bearing malignant tumors (p < 0.05) and a significant dose-related increased incidence (p < 0.01) of hematopoietic neoplasias in males, in particular at the dose levels of 2,000 ppm (p < 0.01) and 16,000 ppm (p < 0.01). Conclusions These findings do not support previous data that sucralose is biologically inert. More studies are necessary to show the safety of sucralose, including new and more adequate carcinogenic bioassay on rats. Considering that millions of people are likely exposed, follow-up studies are urgent. PMID:27078173

Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice.

PubMed

M, Soffritti; M, Padovani; E, Tibaldi; L, Falcioni; F, Manservisi; M, Lauriola; L, Bua; M, Manservigi; F, Belpoggi

2016-01-01

Sucralose is an organochlorine artificial sweetener approximately 600 times sweeter than sucrose and used in over 4,500 products. Long-term carcinogenicity bioassays on rats and mice conducted on behalf of the manufacturer have failed to show the evidence of carcinogenic effects. The aim of this study was to evaluate the carcinogenic effect of sucralose in mice, using a sensitive experimental design. Five groups of male (total n = 457) and five groups female (total n = 396) Swiss mice were treated from 12 days of gestation through the lifespan with sucralose in their feed at concentrations of 0, 500, 2,000, 8,000, and 16,000 ppm. We found a significant dose-related increased incidence of males bearing malignant tumors (p < 0.05) and a significant dose-related increased incidence (p < 0.01) of hematopoietic neoplasias in males, in particular at the dose levels of 2,000 ppm (p < 0.01) and 16,000 ppm (p < 0.01). These findings do not support previous data that sucralose is biologically inert. More studies are necessary to show the safety of sucralose, including new and more adequate carcinogenic bioassay on rats. Considering that millions of people are likely exposed, follow-up studies are urgent.

Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).

PubMed

Alam, N N; White, D A; Narang, S K; Daniels, I R; Smart, N J

2016-02-01

There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies

Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

PubMed

Sheikhzadeh, Fahime; Ward, Rabab K; Carraro, Anita; Chen, Zhao Yang; van Niekerk, Dirk; Miller, Dianne; Ehlen, Tom; MacAulay, Calum E; Follen, Michele; Lane, Pierre M; Guillaud, Martial

2015-10-24

Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions. We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software. The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 μm below the epithelial surface were respectively 100, 100, and 92 %. Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical

Evaluation of a risk index for advanced proximal neoplasia of the colon.

PubMed

Ruco, Arlinda; Stock, David; Hilsden, Robert J; McGregor, S Elizabeth; Paszat, Lawrence F; Saskin, Refik; Rabeneck, Linda

2015-01-01

A clinical risk index that uses distal colorectal findings at flexible sigmoidoscopy (FS) in conjunction with easily determined risk factors for advanced proximal neoplasia (APN) may be useful for tailoring or prioritizing screening with colonoscopy. To conduct an external evaluation of a previously published risk index in a large, well-characterized cohort. Cross-sectional. Teaching hospital and colorectal cancer screening center. A total of 5139 asymptomatic persons aged 50 to 74 (54.9% women) with a mean age (±SD) of 58.3 (±6.2) years. Between 2003 and 2011, all participants underwent a complete screening colonoscopy and removal of all polyps. Participants were classified as low, intermediate, or high risk for APN, based on their composite risk index scores. The concordance or c-statistic was used to measure discriminating ability of the risk index. A total of 167 persons (3.2%) had APN. The prevalence of those with APN among low-, intermediate-, and high-risk categories was 2.1%, 2.9%, and 6.5%, respectively. High-risk individuals were 3.2 times more likely to have APN compared with those in the low-risk category. The index did not discriminate well between those in the low- and intermediate-risk categories. The c-statistic for the overall index was 0.62 (95% confidence interval, 0.58-0.66). Distal colorectal findings were derived from colonoscopies and not FS itself. The risk index discriminated between those at low risk and those at high risk, but it had limited ability to discriminate between low- and intermediate-risk categories for prevalent APN. Information on other risk factors may be needed to tailor, or prioritize, access to screening colonoscopy. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry

PubMed Central

Haidry, Rehan J; Butt, Mohammed A; Dunn, Jason; Banks, Matthew; Gupta, Abhinav; Smart, Howard; Bhandari, Pradeep; Smith, Lesley Ann; Willert, Robert; Fullarton, Grant; John, Morris; Di Pietro, Massimo; Penman, Ian; Novelli, Marco; Lovat, Laurence B

2013-01-01

AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data. PMID:24106401

MicroRNAs in the development and neoplasia of the mammary gland.

PubMed

Jena, Manoj Kumar

2017-01-01

Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes. Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple negative breast cancer cases which can be diagnostic biomarker for this subtype of cancer.  This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us to understand the molecular details of mammary gland biology, as well as miRs that could be therapeutic targets of breast cancer.

Toxicity and response in cats with neoplasia treated with toceranib phosphate.

PubMed

Harper, Aaron; Blackwood, Laura

2017-06-01

Objectives Toceranib phosphate is a tyrosine kinase inhibitor licensed for the treatment of non-resectable Patnaik grade II/III recurrent cutaneous mast cell tumours in dogs. There is no information in cats regarding the tolerated dose, toxicity or tumour response of this drug. The aim of this study was to analyse retrospectively a cohort of cats with advanced neoplasia treated with toceranib to identify toxicity and response. Methods The medical records of the Small Animal Teaching Hospital were reviewed. Cats were included if they had received toceranib for at least 2 weeks for the treatment of histologically or cytologically confirmed neoplastic disease, and had at least one set of monitoring blood tests (haematology, biochemistry) performed after baseline tests. Toxicity was graded according to the Veterinary Comparative Oncology Group - common terminology criteria for adverse events(VCOG-CTCAE) and response was measured according to Response Evaluation In Solid Tumors (RECIST) criteria. Results Fourteen cats met the inclusion criteria, the majority of which (13/14) had received previous therapy (surgery, radiotherapy, chemotherapy). The most common tumour types were mast cell tumours or malignant epithelial tumours. Toxicity occurred in 10/14 cats - 10 cats had mild myelosuppression or gastrointestinal effects. Two cats developed severe hepatoxicity. One cat died from congestive heart failure, although whether this was related to toceranib therapy is unknown. Regarding response, one cat achieved complete response; two cats achieved partial response and five cats achieved stable disease: overall biological response rate was 57.1%. All of the cats that achieved either partial or complete response were treated for mast cell disease. Overall median duration of response was 90 days (range 14-570 days). None of the cats with squamous cell carcinoma achieved a response. Conclusions and relevance Toceranib phosphate is generally well tolerated in cats, with toxicity

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

PubMed Central

Isidro, Raymond A; Cruz, Myrella L; Isidro, Angel A; Baez, Axel; Arroyo, Axel; González-Marqués, William A; González-Keelan, Carmen; Torres, Esther A; Appleyard, Caroline B

2015-01-01

AIM: To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS: Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS: On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to

Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.

PubMed

Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo

2008-12-01

Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

[A clinical study on the complications associated with laser therapy for cervical neoplasia].

PubMed

Wakita, K; Kuramoto, H; Sasaki, N; Izumi, T; Nishijima, M

1994-07-01

Six hundred and fifty-nine patients with cervical neoplasia were treated by either vaporization (395 patients) or excisional conization (264 patients) with various Lasers. The complications associated with the therapies were examined with reference to the Laser sources and in the local anesthesia and non anesthesia groups. Six hundred and thirty-nine patients were treated on an outpatient basis without local anesthesia (37.7%) or with local anesthesia (62.3%). During the procedures, the patients complained of pain and a hot sensation in the lower abdomen in 64.6% in the vaporization (vapor) group and 60.7% in the conization (cone) group. In the local anesthesia group, 2.9% of the vapor and 4.0% of cone group complained of nothing. Uncontrollable bleeding during the procedures was most common in 12.8% and 32.3% in the CO2 vapor and cone groups, respectively. Misirradiation of the vaginal wall and vulva occurred in 3.3% in all vapor groups. On the other hand, the incidence of burns to both areas in all cone groups was 7.2%. The patients who were given an analgesic were 1.3% in all vapor groups and 2.5% in all cone groups. Delayed bleeding in those who received some treatment to stop it occurred in 14.7% in all vapor groups and also in 11.0% in all cone groups. Cervical stenosis was seen in 3.8% in all vapor groups and in 8.6% in all cone groups. No infection of the lasered site was observed in the vapor groups, but was observed in 0.8% in the cone groups. The culture test showed both E. coli positive.

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

PubMed

van Beurden, M; de Craen, A J; de Vet, H C; Blaauwgeers, J L; Drillenburg, P; Gallee, M P; de Kraker, N W; Lammes, F B; ten Kate, F J

1999-11-01

To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice.

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

PubMed Central

van Beurden, M; de Craen, A J; de Vet, H C; Blaauwgeers, J L; Drillenburg, P; Gallee, M P; de Kraker, N W; Lammes, F B; ten Kate, F J

1999-01-01

AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. METHODS: 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. RESULTS: Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. CONCLUSIONS: The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice. Images PMID:10690171

Review: Anal Intraepithelial Neoplasia in HIV-Infected Men Who Have Sex with Men: Is Screening and Treatment Justified?

PubMed

Wasserman, Peter; Rubin, David S; Turett, Glenn

2017-06-01

Anal squamous cell carcinoma (SCC) is the fourth most prevalent cancer in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Human papillomavirus (HPV) has been detected in over 90% of anal carcinoma biopsy specimens from MSM, and is considered a necessary, but alone, insufficient factor for carcinogenesis. Anal intraepithelial neoplasia (AIN) may be precursive for SCC, and screening cytology with referral of persons with abnormality for high-resolution anoscopy-guided biopsy, and AIN treatment, has been recommended for prevention. In the absence of either randomized controlled trials or surveillance data demonstrating a reduction in anal SCC incidence, these recommendations were based on analogy with cervical cancer. HPV-mediated genetic changes associated with cervical cancer, and aneuploidy, have been documented in AIN. However, little data exist on the rate of AIN progression to SCC. The treatment of AIN is frequently prolonged and not curative, and if routinized in the care of HIV-infected MSM, would likely be recurring well into their sixth decade of life. Clinical trials demonstrating a reduction in invasive anal carcinoma incidence, as well as acceptable morbidity with repeated AIN destruction, are needed before asking our patients to commit to routine treatment.

Ultra High-Resolution Anterior Segment Optical Coherence Tomography in the Diagnosis and Management of Ocular Surface Squamous Neoplasia

PubMed Central

Thomas, Benjamin J.; Galor, Anat; Nanji, Afshan A.; Sayyad, Fouad El; Wang, Jianhua; Dubovy, Sander R.; Joag, Madhura G.; Karp, Carol L.

2014-01-01

The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development. PMID:24439046

A comparative evaluation of Raman and fluorescence spectroscopy for optical diagnosis of oral neoplasia

NASA Astrophysics Data System (ADS)

Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.

2011-08-01

We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.

Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.

PubMed

Rodríguez, Ana Cecilia; Schiffman, Mark; Herrero, Rolando; Hildesheim, Allan; Bratti, Concepción; Sherman, Mark E; Solomon, Diane; Guillén, Diego; Alfaro, Mario; Morales, Jorge; Hutchinson, Martha; Katki, Hormuzd; Cheung, Li; Wacholder, Sholom; Burk, Robert D

2010-03-03

The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

PubMed

Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

2018-02-01

The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P < 0.05). Multivariable analysis found that only the expression levels of HR-HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

[Human papillomavirus infection and cervical intraepithelial neoplasia morbidity of women from different occupations in Shenzhen city, China].

PubMed

Tang, Hui-ru; Zhou, Yan-qiu; Wu, Lan-na; Liu, Zhi-hong; Zhang, Li-jie; Wu, Rui-fang

2007-10-01

To investigate the human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) morbidity of women from different occupations in Shenzhen city. 2045 women of five kinds of occupation in Shenzhen city, including 130 teachers, 385 workers, 316 service women, 199 poverish women, 420 doctors or nurses and 595 general residents were included. We screened these women by methods of detecting high risk HPV of hc2 combing with LCT. Women with screening positive results were diagnosed CIN by colposcopic biopsy. (1) High risk factors on HPV infection rate in different occupations were different with the highest in service occupation (19.3%) while the lowest appeared in medical workers (11.9%). (2) In those 2045 women, we found 199 cervical lesions including pathological HPV infection, CIN1, 2, 3 and cervical cancers, with morbidity rates as 4.11%, 3.28%, 1.67%, 0.54% and 0.15% respectively. Along with the progress of the cervical lesions, the morbidity decreased. (3) The morbidity rates of CIN in different occupations were different, with the highest of HSIL in service occupation and the lowest in teachers. Women of different occupations in Shenzhen city had different high risk HPV infection rates and CIN morbidity. The HPV infection rate and HSIL morbidity were highest among women having service related jobs.

Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

PubMed

Marcos Lopes, Ana Cristina; Campaner, Adriana Bittencourt; Henrique, Laílca Quirino

2016-01-01

To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer. © 2016 S. Karger AG, Basel.

Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia.

PubMed

Hillemanns, Peter; Einstein, Mark H; Iversen, Ole Erik

2015-02-01

Current treatments for high-grade cervical intraepithelial neoplasia (CIN2/3) are mainly excisional procedures, which are associated with significant side effects and pose risks for future pregnancies. An effective and safe therapy is needed to reduce the requirement for surgical interventions in women of reproductive age. This review looks at the pharmacokinetic and clinical data for topical hexaminolevulinate (HAL) photodynamic therapy (PDT), which is currently entering late phase clinical trials for high-grade CIN. The authors include published studies in patients and volunteers but laboratory and animal studies have been excluded as have studies on other porphyrins such as Photofrin, 5-aminolevulinic acid, methyl aminolevulinate and studies reporting other clinical applications for HAL. Topical HAL PDT has potential as a non-surgical tissue-preserving treatment for CIN and persistent oncogenic human papilloma virus infections. HAL PDT selectively treats the entire epithelial sheet, without the tissue destruction seen in excisional procedures. The authors believe that this treatment could replace surgery in a large proportion of patients. It would be of particular value to the high percentage of women who are interested in future child-bearing. If the treatment is approved, it is very likely that physicians will want to use this treatment, as many patients will be keen to consider a non-surgical option.

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

PubMed Central

Cole, John J.; Nelson, David M.; Dikovskaya, Dina; Faller, William J.; Vizioli, Maria Grazia; Hewitt, Rachael N.; Anannya, Orchi; McBryan, Tony; Manoharan, Indrani; van Tuyn, John; Morrice, Nicholas; Pchelintsev, Nikolay A.; Ivanov, Andre; Brock, Claire; Drotar, Mark E.; Nixon, Colin; Clark, William; Sansom, Owen J.; Anderson, Kurt I.; King, Ayala; Blyth, Karen

2014-01-01

Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression. PMID:25512559

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia.

PubMed

Rai, Taranjit Singh; Cole, John J; Nelson, David M; Dikovskaya, Dina; Faller, William J; Vizioli, Maria Grazia; Hewitt, Rachael N; Anannya, Orchi; McBryan, Tony; Manoharan, Indrani; van Tuyn, John; Morrice, Nicholas; Pchelintsev, Nikolay A; Ivanov, Andre; Brock, Claire; Drotar, Mark E; Nixon, Colin; Clark, William; Sansom, Owen J; Anderson, Kurt I; King, Ayala; Blyth, Karen; Adams, Peter D

2014-12-15

Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression. © 2014 Rai et al.; Published by Cold Spring Harbor Laboratory Press.

Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering

PubMed Central

Mourant, Judith R.; Bocklage, Thérese J.; Powers, Tamara M.; Greene, Heather M.; Dorin, Maxine H.; Waxman, Alan G.; Zsemlye, Meggan M.; Smith, Harriet O.

2009-01-01

Objective To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. Materials and Methods A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. Results Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. Conclusions The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating ”see and treat” protocols is a longer term goal. Improvements in accuracy are essential. PMID:20694193

Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting.

PubMed

Ho, Gloria Y F; Einstein, Mark H; Romney, Seymour L; Kadish, Anna S; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D

2011-10-01

: This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. : Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. : At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. : Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis.

PubMed

Taxa, Luis; Jeronimo, Jose; Alonzo, Todd A; Gage, Julia; Castle, Philip E; Cremer, Miriam L; Felix, Juan C

2018-01-01

To determine the involvement of cervical intraepithelial neoplasia grade 3 (CIN3) in a population of women in a lower-resource setting. One hundred twelve consecutive cone excision specimens with histological diagnosis of CIN3 were retrieved from the National Institute of Neoplastic Diseases in Lima Peru. Two pathologists independently evaluated each specimen microscopically and confirmed 107 cases that could be measured by optical micrometry. Depth and breadth of the lesions were measured microscopically. The mean maximal depth of cervical involvement by CIN3 was 2 ± 0.13 mm; depth was less than 3.5 mm in 89.7% of cases and less than 5 mm in 93.5%. Mean breadth of CIN3 was 7.3 ± 4.4 mm; breadth was less than 15.9 mm in 95% of cases and less than 20.5 mm in 99.7%. The correlation coefficient between breadth and depth of CIN3 was 0.61. No significant correlation was found between age and depth. Depth of CIN3 involvement in a developing country is significantly deeper than that reported in the United States. Treatment selection for women with CIN3 and risk of treatment failure may vary between developing and developed countries because of the difference in the depth of lesions. Countries with underscreened populations need to consider the increased disease severity in devising treatment strategies.

Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion.

PubMed

Erickson-Johnson, Michele R; Chou, Margaret M; Evers, Barbara R; Roth, Christopher W; Seys, Amber R; Jin, Long; Ye, Ying; Lau, Alan W; Wang, Xiaoke; Oliveira, Andre M

2011-10-01

Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event. © 2011 USCAP, Inc All rights reserved

The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?

PubMed

Mitra, Anita; MacIntyre, David A; Marchesi, Julian R; Lee, Yun S; Bennett, Phillip R; Kyrgiou, Maria

2016-11-01

The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.

Quality audit of colonoscopy reports amongst patients screened or surveilled for colorectal neoplasia.

PubMed

Beaulieu, Daphnée; Barkun, Alan; Martel, Myriam

2012-07-21

To complete a quality audit using recently published criteria from the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. Consecutive colonoscopy reports of patients at average/high risk screening, or with a prior colorectal neoplasia (CRN) by endoscopists who perform 11 000 procedures yearly, using a commercial computerized endoscopic report generator. A separate institutional database providing pathological results. Required documentation included patient demographics, history, procedure indications, technical descriptions, colonoscopy findings, interventions, unplanned events, follow-up plans, and pathology results. Reports abstraction employed a standardized glossary with 10% independent data validation. Sample size calculations determined the number of reports needed. Two hundreds and fifty patients (63.2 ± 10.5 years, female: 42.8%, average risk: 38.5%, personal/family history of CRN: 43.3%/20.2%) were scoped in June 2009 by 8 gastroenterologists and 3 surgeons (mean practice: 17.1 ± 8.5 years). Procedural indication and informed consent were always documented. 14% provided a previous colonoscopy date (past polyp removal information in 25%, but insufficient in most to determine surveillance intervals appropriateness). Most procedural indicators were recorded (exam date: 98.4%, medications: 99.2%, difficulty level: 98.8%, prep quality: 99.6%). All reports noted extent of visualization (cecum: 94.4%, with landmarks noted in 78.8% - photodocumentation: 67.2%). No procedural times were recorded. One hundred and eleven had polyps (44.4%) with anatomic location noted in 99.1%, size in 65.8%, morphology in 62.2%; removal was by cold biopsy in 25.2% (cold snare: 18%, snare cautery: 31.5%, unrecorded: 20.7%), 84.7% were retrieved. Adenomas were noted in 24.8% (advanced adenomas: 7.6%, cancer: 0.4%) in this population with varying previous colonic investigations. This audit reveals lacking reported items, justifying additional research to

Quality audit of colonoscopy reports amongst patients screened or surveilled for colorectal neoplasia

PubMed Central

Beaulieu, Daphnée; Barkun, Alan; Martel, Myriam

2012-01-01

AIM: To complete a quality audit using recently published criteria from the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. METHODS: Consecutive colonoscopy reports of patients at average/high risk screening, or with a prior colorectal neoplasia (CRN) by endoscopists who perform 11 000 procedures yearly, using a commercial computerized endoscopic report generator. A separate institutional database providing pathological results. Required documentation included patient demographics, history, procedure indications, technical descriptions, colonoscopy findings, interventions, unplanned events, follow-up plans, and pathology results. Reports abstraction employed a standardized glossary with 10% independent data validation. Sample size calculations determined the number of reports needed. RESULTS: Two hundreds and fifty patients (63.2 ± 10.5 years, female: 42.8%, average risk: 38.5%, personal/family history of CRN: 43.3%/20.2%) were scoped in June 2009 by 8 gastroenterologists and 3 surgeons (mean practice: 17.1 ± 8.5 years). Procedural indication and informed consent were always documented. 14% provided a previous colonoscopy date (past polyp removal information in 25%, but insufficient in most to determine surveillance intervals appropriateness). Most procedural indicators were recorded (exam date: 98.4%, medications: 99.2%, difficulty level: 98.8%, prep quality: 99.6%). All reports noted extent of visualization (cecum: 94.4%, with landmarks noted in 78.8% - photodocumentation: 67.2%). No procedural times were recorded. One hundred and eleven had polyps (44.4%) with anatomic location noted in 99.1%, size in 65.8%, morphology in 62.2%; removal was by cold biopsy in 25.2% (cold snare: 18%, snare cautery: 31.5%, unrecorded: 20.7%), 84.7% were retrieved. Adenomas were noted in 24.8% (advanced adenomas: 7.6%, cancer: 0.4%) in this population with varying previous colonic investigations. CONCLUSION: This audit reveals lacking reported items

A cost analysis of first-line chemotherapy for low-risk gestational trophoblastic neoplasia.

PubMed

Shah, Neel T; Barroilhet, Lisa; Berkowitz, Ross S; Goldstein, Donald P; Horowitz, Neil

2012-01-01

To determine the optimal approach to first-line treatment for low-risk gestational trophoblastic neoplasia (GTN) using a cost analysis of 3 commonly used regimens. A decision tree of the 3 most commonly used first-line low-risk GTN treatment strategies was created, accounting for toxicities, response rates and need for second- or third-line therapy. These strategies included 8-day methotrexate (MTX)/folinic acid, weekly MTX, and pulsed actinomycin-D (act-D). Response rates, average number of cycles needed for remission, and toxicities were determined by review of the literature. Costs of each strategy were examined from a societal perspective, including the direct total treatment costs as well as the indirect lost labor production costs from work absences. Sensitivity analysis on these costs was performed using both deterministic and probabilistic cost-minimization models with the aid of decision tree software (TreeAge Pro 2011, TreeAge Inc., Williamstown, Massachusetts). We found that 8-day MTX/folinic acid is the least expensive to society, followed by pulsed act-D ($4,867 vs. $6,111 average societal cost per cure, respectively), with act-D becoming more favorable only with act-D per-cycle cost <$231, or response rate to first-line therapy > 99%. Weekly MTX is the most expensive first-line treatment strategy to society ($9,089 average cost per cure), despite being least expensive to administer per cycle, based on lower first-line response rate. Absolute societal cost of each strategy is driven by the probability of needing expensive third-line multiagent chemotherapy, however relative cost differences are robust to sensitivity analysis over the reported range of cycle number and response rate for all therapies. Based on similar efficacy and lower societal cost, we recommend 8-day MTX/folinic acid for first-line treatment of low-risk GTN.

Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

PubMed

Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

2015-11-01

To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CI<0.01%-0.7%) after a partial hydatidiform mole, and in 0/13 patients (0%; 95% CI 0%-27%) after a twin molar pregnancy. The median time to GTN diagnosis after hCG normalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CI<0.01%-0.5%; p=0.008). All patients presented with symptoms at the time of GTN diagnosis. GTN after spontaneous hCG normalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion

PubMed Central

Hall, Michael J; Innocent, Julie; Rybak, Christina; Veloski, Colleen; Scott, Walter J; Wu, Hong; Ridge, John A; Hoffman, John P; Borghaei, Hossein; Turaka, Aruna; Daly, Mary B

2015-01-01

Introduction Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). Discussion Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that

Discrepancy between endoscopic forceps biopsy and endoscopic resection in gastric epithelial neoplasia.

PubMed

Lim, Hyun; Jung, Hwoon-Yong; Park, Young Soo; Na, Hee Kyong; Ahn, Ji Yong; Choi, Ji Young; Lee, Jeong Hoon; Kim, Mi-Young; Choi, Kwi-Sook; Kim, Do Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho

2014-04-01

Endoscopic forceps biopsy (EFB) is a major diagnostic procedure for gastric epithelial neoplasia (GEN). However, discrepancy between the result of EFB and endoscopic resection (ER) is not uncommon. Thus, there is controversy over whether specimens obtained by EFB are optimal for diagnosis of GEN. We investigated the discrepancy between EFB and ER in the diagnosis of GEN. A total of 1,850 GEN cases were histologically diagnosed with EFB, including 954 low-grade dysplasias (LGDs), 315 high-grade dysplasias (HGDs), and 581 carcinomas. Following diagnosis with EFB, all patients were treated with ER. We retrospectively reviewed the pathologic findings and patient characteristics and analyzed predictors for the discrepancy between the two procedures (largest diameter, number of biopsy fragments, number of biopsy fragments/largest diameter, location, macroscopic type, color, surface unevenness, and erosion). The overall discrepancy rate between EFB and ER was 31.7 % (587/1,850). Among the discordant group, 440 (23.9 %) cases showed a higher grade of disease after ER; 229 of the 954 LGDs (24.0 %) were diagnosed as HGD or carcinoma, 166 of the 315 HGDs (52.7 %) as carcinoma, and 45 of the 581 differentiated carcinomas (7.7 %) as undifferentiated carcinoma. In the LGD group with EFB, the largest diameter (≥1.8 cm; P < 0.001), surface unevenness (P = 0.014), and depressed macroscopic type (P < 0.001) were factors associated with discrepancy. In the carcinoma group with EFB, flat macroscopic type (P = 0.043) was the only significant factor. In the HGD group with EFB, there were no significant factors for discrepancy. EFB can be insufficient for diagnosing GENs, and ER can be considered not only as treatment but also as a diagnostic modality in GEN. It is especially pertinent to all cases of HGD regardless of their endoscopic features and to cases of LGDs with the largest lesion diameter ≥1.8 cm, surface unevenness, or a depressed macroscopic type.

Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

PubMed

Garland, Suzanne M; Paavonen, Jorma; Jaisamrarn, Unnop; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Castellsagué, Xavier; Teixeira, Júlio C; Skinner, S Rachel; Hedrick, James; Limson, Genara; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Del Rosario-Raymundo, M Rowena; Catteau, Grégory; Descamps, Dominique; Struyf, Frank; Lehtinen, Matti; Dubin, Gary

2016-12-15

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+. © 2016 UICC.

High grade anal intraepithelial neoplasia among HIV-1-infected men screening for a multi-center clinical trial of a human papillomavirus vaccine

PubMed Central

Wilkin, Timothy; Lee, Jeannette Y.; Lensing, Shelly Y.; Stier, Elizabeth A.; Goldstone, Stephen E.; Berry, J. Michael; Jay, Naomi; Aboulafia, David M.; Einstein, Mark H.; Saah, Alfred; Mitsuyasu, Ronald T.; Palefsky, Joel M.

2013-01-01

Purpose High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. HPV vaccination holds great promise for preventing anal cancer. Methods We examined 235 HIV-1-infected men screening for participation in a multi-site clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology, and high resolution anoscopy with biopsies of visible lesions to assess for HGAIN. Results HPV 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV 16 detection compared to those without (38% vs. 17%, P=.01). Use of antiretroviral therapy, nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN. Conclusion HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN. PMID:23611828

Metformin and Anti-Cancer Therapeutics: Hopes for a More Enhanced Armamentarium Against Human Neoplasias?

PubMed

Christodoulou, Maria-Ioanna; Scorilas, Andreas

2017-01-01

Metformin, a natural product from Galega officinalis, is an oral drug, now in the forefront of the therapeutic management of type-2 diabetes mellitus. A series of clinical observations of the last decades, support that metformin may contribute to lowering the risk of cancer development in diabetic patients, and also to improvement of response-to-therapy and survival in individuals with certain types of malignancies. Moreover, several preclinical in vitro and in vivo data indicate that metformin indeed exerts anti-proliferative capacities upon tumor cells mediated through a variety of mechanisms. Interestingly, metformin has been shown to act in synergy with certain anti-cancer agents and also to overcome chemo- and/or radio-resistance of various types of tumors, providing a hopeful rationale for novel therapeutic strategies against cancer development and progression. However, this remains an issue of controversy, since significant contradictions exist among the available data. Limitations of preclinical studies and caveats of epidemiological works, together with significant variances among the several types of cancer and the fact that the mode of metformin's action is largely unknown, make longitudinal surveys urgently needed. Now, a plethora of large clinical trials are active worldwide, aiming at determining the effect of metformin in the prevention or prognosis of a variety of human cancers. If encouraging results arise, metformin will be an attractive candidate adjuvant in the management of human neoplasias, due to its safety, tolerability and low-cost, expected to mitigate adverse effects and no-response parameters of current anti-cancer therapeutics, thus improving the quality of life and survival of cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study

PubMed Central

Kalliala, Ilkka; Anttila, Ahti; Nieminen, Pekka; Halttunen, Mervi; Dyba, Tadeusz

2014-01-01

We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97–1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03–1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01–1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15–1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15–1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings. PMID:25146172

Type 2 diabetes mellitus and colorectal neoplasia risk in Hispanics: a case-control study.

PubMed

Díaz-Algorri, Yaritza; Lozada, María Eugenia; López, Sofía M; Bertrán-Rodríguez, Carlos E; González-Hernández, Cinthia M; González, Dilka; Pérez-Cardona, Cynthia M; Hernández, Jessica; Pedrosa, Carmen; Toro, Doris H; González-Pons, María; Cruz-Correa, Marcia

2015-01-01

There is inconclusive evidence regarding the potential link between diabetes mellitus (DM) and colorectal cancer (CRC). Associations between type 2 DM and colorectal neoplasia (CRN; colorectal cancer and/or adenomas) have not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM. This study aims to assess the association between type 2 DM and CRN in Hispanics. Hispanics with incident CRN and colonoscopy-negative controls from 2005 to 2009 were evaluated. Diagnosis of type 2 DM was established by previous medical diagnosis and/or use of DM treatments. Unconditional logistic regression was performed to estimate odds ratios for the association between type 2 DM and CRN. A total of 451 participants (mean age 61.1±11.9years, 59.6 % men) were evaluated (218 with incident CRC, 77 with colorectal adenomas, and 156 colonoscopy-negative controls). The prevalence of type 2 DM in this study was 25.1%. After adjusting for potential confounding variables, women with type 2 DM were 2.74 (95% CI: 0.94-7.99) times more likely to have CRN and 4.83 times more likely to present with proximal colonic CRN (95% CI: 1.25-18.58) than women without type 2 DM. No statistically significant associations were found between type 2 DM and CRN among men. An increased odds for CRN and proximal location of CRN was observed among Hispanic women with type 2 DM. Since DM is a highly prevalent disease in this population, adherence to routine CRC screening is of outmost importance. Copyright © 2015 Elsevier Inc. All rights reserved.

Recutting prostate needle core biopsies with high grade prostatic intraepithelial neoplasia increases detection of adenocarcinoma.

PubMed

Rapp, David E; Msezane, Lambda P; Reynolds, W Stuart; Lotan, Tamara L; Obara, Piotr; O'Connor, R Corey; Taxy, Jerome B; Gerber, Glenn S; Zagaja, Gregory P

2009-02-01

We sought to evaluate the ability of biopsy core recutting to increase cancer detection in patients with high grade prostatic intraepithelial neoplasia (HGPIN). This prospective study encompasses all patients undergoing 12 core TRUS guided prostate biopsy between February 2004 and January 2007. In patients with HGPIN on initial biopsy, the paraffin blocks were resampled for cancer by additional deeper levels per core. Additional analysis was performed in the patients with HGPIN in order to detect whether significant differences in prebiopsy variables were associated with patients subsequently found to have benign versus carcinoma on recutting. Last, the costs associated with this procedure were studied. Forty of 584 (6.8%) patients undergoing prostate biopsy were found to have HGPIN in the absence of prostatic adenocarcinoma on initial histopathology. Following recutting, 12.5% (5/40) of these patients were found to have prostatic adenocarcinoma not previously detected. Of the remaining 35 patients, 18 underwent repeat biopsy. Of these, five patients were found to have adenocarcinoma and three were found to have persistent HGPIN. The PSA, PSA density (PSAD), and PSA velocity (PSAV) prior to initial biopsy were not statistically different when comparing patients found to have benign tissue versus carcinoma on recutting. In patients with HGPIN, at our institution, recutting the biopsy would yield a cost savings of $436/patient as opposed to universal rebiopsy. Our data suggest that prostate biopsy recutting may increase cancer detection in patients initially found to have HGPIN. Additionally, a significant cost savings is associated with the recutting protocol.

Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia

PubMed Central

Daayana, S; Elkord, E; Winters, U; Pawlita, M; Roden, R; Stern, P L; Kitchener, H C

2010-01-01

Background: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. Methods: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. Results: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. Conclusion: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically. PMID:20234368

High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene.

PubMed

Liu, Jehnan; Ramakrishnan, Sadeesh K; Khuder, Saja S; Kaw, Meenakshi K; Muturi, Harrison T; Lester, Sumona Ghosh; Lee, Sang Jun; Fedorova, Larisa V; Kim, Andrea J; Mohamed, Iman E; Gatto-Weis, Cara; Eisenmann, Kathryn M; Conran, Philip B; Najjar, Sonia M

2015-03-01

Association between prostate cancer and obesity remains controversial. Allelic deletions of PTEN, a tumor suppressor gene, are common in prostate cancer in men. Monoallelic Pten deletion in mice causes low prostatic intraepithelial neoplasia (mPIN). This study tested the effect of a hypercaloric diet on prostate cancer in Pten (+/-) mice. 1-month old mice were fed a high-calorie diet deriving 45% calories from fat for 3 and 6 months before prostate was analyzed histologically and biochemically for mPIN progression. Because Pten (+/-) mice are protected against diet-induced insulin resistance, we tested the role of insulin on cell growth in RWPE-1 normal human prostatic epithelial cells with siRNA knockdown of PTEN. In addition to activating PI3 kinase/Akt and Ras/MAPkinase pathways, high-calorie diet causes neoplastic progression, angiogenesis, inflammation and epithelial-mesenchymal transition. It also elevates the expression of fatty acid synthase (FAS), a lipogenic gene commonly elevated in progressive cancer. SiRNA-mediated downregulation of PTEN demonstrates increased cell growth and motility, and soft agar clonicity in addition to elevation in FAS in response to insulin in RWPE-1 normal human prostatic cells. Downregulating FAS in addition to PTEN, blunted the proliferative effect of insulin (and IL-6) in RWPE-1 cells. High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis.

[Screening of anal intraepithelial neoplasia in risk groups: descriptive study of sexual habits and other sexual transmitted infections].

PubMed

Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Frieyro-Elicegui, Marta; Rivas-Ruiz, Francisco; Robles, Luis; de Troya, Magdalena

2014-02-20

Anal intraepithelial neoplasia is considered a precursor lesion of anal squamous carcinoma. The population with increased risk of this conditions are immunocompromised individuals, especially HIV-infected, with anal sex practices. The aim of this study was to describe the sexual habits of patients who were seen in sexually transmitted infections (STIs) consult in our service in whom anal cytology was performed as well as the association of anal dysplasia to other STIs. We performed a retrospective cohort study that included those patients in whom, according to our protocol, anal cytology was performed between 2008 and 2011. Also we conducted a survey on sexual habits and screening for other STIs. Finally, we conducted a descriptive and analytical study assessing bivariate distribution of cytological alterations and grade of anal dysplasia. A total of 347 anal cytologies were performed, and 48.1% were abnormal. Statistically significant differences were found between the presence of condylomata perianal/endoanal, HIV infection, Chlamydia trachomatis infection and the presence of cytologic alterations. There was a high incidence of anal dysplasia in our group of individuals with risky sexual habits; however, it is probably underdiagnosed due to its subclinical nature and lack of a well-established screening protocol. Copyright © 2013 Elsevier España, S.L. All rights reserved.

ConsPred: a rule-based (re-)annotation framework for prokaryotic genomes.

PubMed

Weinmaier, Thomas; Platzer, Alexander; Frank, Jeroen; Hellinger, Hans-Jörg; Tischler, Patrick; Rattei, Thomas

2016-11-01

The rapidly growing number of available prokaryotic genome sequences requires fully automated and high-quality software solutions for their initial and re-annotation. Here we present ConsPred, a prokaryotic genome annotation framework that performs intrinsic gene predictions, homology searches, predictions of non-coding genes as well as CRISPR repeats and integrates all evidence into a consensus annotation. ConsPred achieves comprehensive, high-quality annotations based on rules and priorities, similar to decision-making in manual curation and avoids conflicting predictions. Parameters controlling the annotation process are configurable by the user. ConsPred has been used in the institutions of the authors for longer than 5 years and can easily be extended and adapted to specific needs. The ConsPred algorithm for producing a consensus from the varying scores of multiple gene prediction programs approaches manual curation in accuracy. Its rule-based approach for choosing final predictions avoids overriding previous manual curations. ConsPred is implemented in Java, Perl and Shell and is freely available under the Creative Commons license as a stand-alone in-house pipeline or as an Amazon Machine Image for cloud computing, see https://sourceforge.net/projects/conspred/. thomas.rattei@univie.ac.atSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Photodynamic diagnostics of stress-induced gastrointestinal neoplasia in laboratory animals using 5-aminolevulinic acid and Al-phthalocyanine

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Semyachkina-Glushkovskaya, Oxana; Navolokin, Nikita; Mantareva, Vanya; Angelov, Ivan; Agranovich, Ilana; Khorovodov, Alexander; Shushunova, Natalia; Bodrova, Anastasiya; Fedosov, Ivan; Namykin, Anton; Abdurashitov, Arkady; Avramov, Latchezar

2018-02-01

The main research objective is the development of innovative optical technologies for sensitive diagnosis of early stages of development of stomach cancer and monitoring of stress-induced appearance and development of tumors of the gastrointestinal tract by applying endogenous and exogenous fluorescence spectroscopy modalities. Different mechanisms solely and in combination for evaluation of the joint impact of bioenvironmental factors (stress, Helicobacter pillory, exo-toxins in the food, water, soil and air) were applied to induce gastrointestinal tract (GIT) neoplasia in rats. The transformation of damaged areas of the stomach mucosa into malignancies in all parts of gastrointestinal tract were detected using exogenous fluorescence of photosensitizers - 5-aminolevulinic acid (5-ALA) and aluminum phthalocyanine (Al-Pc). Fluorescent mapping of different organs (liver, spleen, lungs, brain) also was developed - to evaluate the distribution of the photosensitizers in the whole body on the second hour after photosensitizer application by intravenous injection. Fiber-optic probe was used to measure the organs investigated. Fluorescence spectra were detected by microspectrometer USB4000 (OceanOptics Inc., USA), and FS405 LED source on 405 nm was used as excitation source for both types of photosensitizers applied. Diagnostically-important parameters of oximetry, optical coherence tomography and speckle-imaging of the microcirculation of the stomach were also evaluated, to evaluate changes in the blood flow and vascular architecture, during the formation of the initial phases of the neoplasm development.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

InterCon Travel Health: Case B

ERIC Educational Resources Information Center

Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

2010-01-01

InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

Impact of the ConRed program on different cyberbulling roles.

PubMed

Del Rey, Rosario; Casas, José A; Ortega, Rosario

2016-01-01

This article presents results from an evaluation of the ConRed cyberbullying intervention program. The program's impacts were separately determined for the different roles within cyberbullying that students can take, i.e., cyber-victims, cyber-bullies, cyber-bully/victims, and bystanders. The ConRed program is a theory-driven program designed to prevent cyberbullying and improve cyberbullying coping skills. It involves students, teachers, and families. During a 3-month period, external experts conducted eight training sessions with students, two with teachers and one with families. ConRed was evaluated through a quasi-experimental design, in which students from three secondary schools were separated into experimental and control groups. The sample comprised 875 students, aged between 11 and 19 years. More students (n = 586) were allocated to the experimental groups at the specific insistence of the management of all schools; the remainder (n = 289) formed the control. Repeated measures MANOVA showed that cyber victims, cyber aggressors and cyberbully/victims reduced their involvement in cyberbullying. Moreover, cyber-victims and bystanders adjusted their perceptions about their control of personal information on the Internet, and cyber aggressors and bystanders reduced their Internet dependence. The ConRed program had stronger effects on male participants, especially in heightening their affective empathy. © 2015 Wiley Periodicals, Inc.