Abnormal anal cytology risk in women with known genital squamous intraepithelial lesion

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Maria do Socorro Nobre

2016-05-01

Full Text Available The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64. Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5% had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR = 2.46; p = 0.03. In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR = 2.81; p = 0.02. This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer.

Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion: a category with an increased outcome of high-grade lesions: use as a quality assurance measure.

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Nishino, Ha T; Wilbur, David C; Tambouret, Rosemary H

2012-08-01

"Low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) is an increasingly used, equivocal interpretive category in gynecologic cytology. In an effort to evaluate its potential usefulness as a measure of quality assurance, we studied patterns of use of the LSIL-H diagnosis compared with "LSIL" and "high-grade squamous intraepithelial lesion" (HSIL) with corresponding histologic outcomes for 10 cytopathologists in our practice. In our laboratory, while the overall rate of associated cervical intraepithelial neoplasia 2 or greater on histologic follow-up for LSIL-H was intermediate between that of LSIL and HSIL, the outcomes for individual cytopathologists varied widely. Monitoring this particular utilization-outcome data with periodic confidential feedback to individual cytopathologists offers an opportunity for practice improvement within a laboratory and serves as an additional measure of quality assurance. These data may be useful for establishing and/or realigning the diagnostic criteria for this equivocal cytologic interpretation endorsed by a pathology practice.

The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in hiv-positive patients

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Felicidad Gimenez

2011-06-01

showed sensibility of 90%, specificity of 19.23%, positive predictive value of 41.67%, negative predictive value of 75%, and a kappa coefficient of 0.076. From the analyzed lesions, high-grade squamous intraepithelial lesions was more frequently observed in association to dense (68%, flat (61%, smooth (61%, non-papillary (83% and normal vascular pattern (70% acetowhite lesions, while low-grade squamous intraepithelial lesions tended to be associated to dense (66%, flat-raised or raised (68%, granular (59%, non-papillary (62% and normal vascular pattern (53% acetowhite lesions. No statistical significance was observed as to the association of epidemiological characteristics and of most of the investigated anal cancer risk factors and presence of acetowhite lesions or anal squamous intraepithelial lesions. However, anal receptive sex and anal HPV infection were significantly associated to anal squamous intraepithelial lesions (P = 0.0493 and P = 0.006, respectively. CONCLUSION: High-resolution anoscopy demonstrated to be a sensitive, but not specific test for the detection of anal squamous intraepithelial lesions. Risk factors anal receptive sex and anal HPV infection were significantly associated to the presence of anal squamous intraepithelial lesions. Based on high-resolution anoscopy image data, acetowhite lesions relief and surface pattern were prone to distinguish between low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.

The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high-risk male patients.

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Greebon, Leslie J; Avery, Diane L; Prihoda, Thomas J; Valente, Philip T; Policarpio-Nicolas, Maria Luisa C

2014-06-01

While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high-risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin-prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co-factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission. Copyright © 2014 Wiley Periodicals, Inc.

Syndemic synergy of HPV and other sexually transmitted pathogens in the development of high-grade anal squamous intraepithelial lesions

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Jenny C. McCloskey

2017-12-01

Full Text Available Background: Anal intraepithelial neoplasia is associated with high-risk human papillomavirus (hrHPV as a precursor to anal cancer. However, factors other than hrHPV are likely to be involved and further study of cofactors is required because of the possibility of syndemic interactions. Methods: Three hundred and fourteen patients underwent 457 operations. Histopathology and hrHPV testing using the Digene Hybrid Capture 2 (HC 2 method were performed. Demographic factors and sexually transmissible infections (STIs were recorded. Results: Results showed that hrHPV alone was associated with HSIL (OR = 4.65, p < 0.001. None of the other STIs were alone associated with HSIL but amplification of risk was found when hrHPV infection occurred with HIV (OR = 11.1; syphilis (OR = 5.58; HSV 2 (OR = 7.85; gonorrhoea (OR = 6.45 and some other infections. Conclusions: These results suggest that hrHPV is a sufficient cause of anal HSIL. Seropositivity for HIV, HSV 2, T. pallidum, HBV and HCV and a history of gonorrhoea or chlamydia exert a powerful amplifying factor increasing the risk of HSIL above the risk with hrHPV alone. Other co-factors which are associated with an increased risk of HSIL are increased age, male gender, MSM behaviour and self-reported history of more than 50 sexual partners. This pattern of disease in patients with warts is characteristic of a syndemic with potential serious increased risk of anal carcinoma. Keywords: HSIL, Anal warts, Sexually transmissible infections, High-risk HPV, HIV, Syndemic

Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

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Nittaya Phanuphak

Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

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

NARCIS (Netherlands)

Koeneman, M. M.; Kruse, Arnold-Jan; Kooreman, L. F. S.; zur Hausen, Axel; Hopman, Anton H N; Sep, S. J. S.; Van Gorp, T.; Slangen, B. F. M.; van Beekhuizen, H. J.; de Sande, Michiel A. J. van; Gerestein, Cornelis G.; Nijman, H. W.; Kruitwagen, R. F. M. P.

2017-01-01

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

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

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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.

The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women

DEFF Research Database (Denmark)

Tolstrup, Janne; Munk, Christian; Thomsen, Birthe Lykke

2006-01-01

BACKGROUND: Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important...... for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. METHODS: We used baseline information on exposures on 548 high......-risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. RESULTS: Compared with never smokers, the odds ratio for high...

Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

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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.

Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia

International Nuclear Information System (INIS)

Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C.

2010-01-01

The authors report the results of an exclusive low dose rate curie therapy for female patients treated for a grade 3 vaginal intraepithelial neoplasia. They reviewed the medical files of patients treated since 1983, i.e. 28 women. They analysed demographic characteristics, the clinic description of lesions, possible treatments which occurred before this high-grade vaginal intraepithelial neoplasia, possible previous history of cervical or endometrial cancer, curie therapy detailed data, presence of tumorous relapse. According to that, they conclude that a 60 Gy exclusive low- vaginal dose-rate curie-therapy is an efficient and well tolerated treatment for high-grade vaginal intraepithelial neoplasia. Short communication

Secretory leukocyte protease inhibitor expression and high-risk HPV infection in anal lesions of HIV positive patients

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NUOVO, Gerard J.; GRINSZTEJN, Beatriz; FRIEDMAN, Ruth K.; VELOSO, Valdiléa G.; CUNHA, Cynthia B.; COUTINHO, José R.; VIANNA-ANDRADE, Cecilia; OLIVEIRA, Nathalia S.; WOODHAM, Andrew W.; DA SILVA, Diane M.; KAST, W. Martin

2016-01-01

Objective The aim of the current study was to evaluate secretory leukocyte protease inhibitor (SLPI) expression in anal biopsies from HIV-positive (HIV+) individuals, and compare that to anal intraepithelial neoplasia (AIN) diagnoses and human papillomavirus (HPV) status. Design This is a cross-sectional study of a cohort of 54 HIV+ (31 males and 23 females) from an AIDS clinic in Rio de Janeiro, Brazil. Methods The study material consisted of anorectal tissue biopsies obtained from HIV+ subjects, which were used to construct tissue microarray paraffin blocks for immunohistochemical analysis of SLPI expression. Biopsies were evaluated by an expert pathologist and classified as low-grade anal intraepithelial neoplasia (AIN1), high-grade anal intraepithelial neoplasia (AIN2/3), or normal squamous epithelium. Additionally, DNA from the biopsies was extracted and analyzed for the presence of low- or high-risk HPV DNA. Results Histologically normal squamous epithelium from the anorectal region showed strong positive SLPI staining in 17/20 (85%) samples. In comparison, 9/17 (53%) dysplastic squamous epithelial samples from AIN1 patients showed strong SLPI staining, and only 5/17 (29%) samples from AIN2-3 patients exhibited strong SPLI staining, which both were significantly fewer than those from normal tissue (p=0.005). Furthermore, there was a significantly higher proportion of samples in which oncogenic high-risk HPV genotypes were detected in low SLPI expressing tissues than that in tissues with high SLPI expression (p=0.040). Conclusion Taken together these results suggest that low SLPI expression is associated with high-risk HPV infections in the development of AIN. PMID:27149102

PREVALENCE OF HUMAN PAPILLOMAVIRUS GENOTYPES IN LOW AND HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS AT CERVICAL TISSUE

OpenAIRE

Prasetyo, Rizki Eko; Mastutik, Gondo; Mustokoweni, Sjahjenny

2017-01-01

HPV infection is known to cause cervical cancer. This study aimed to identify the variant of HPV genotypes of cervical precancerous lesions from low grade squamous intraepithelial lesion  (LSIL) and high grade squamous intraepithelial lesion (HSIL). This was an explorative study using formalin fix paraffin embedded (FFPE) from cervical precancerous lesions at Dr. Soetomo Hospital, Surabaya. DNA was extracted from FFPE and hybridized for HPV genotyping using Ampliquality HPV Type Express kit (...

Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men

NARCIS (Netherlands)

Richel, O.; Wieland, U.; de Vries, H. J. C.; Brockmeyer, N. H.; van Noesel, C.; Potthoff, A.; Prins, J. M.; Kreuter, A.

2010-01-01

Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV) induced potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). So far, only a few prospective studies have been performed on the topical

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

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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.

Patients with newly diagnosed cervical cancer should be screened for anal human papilloma virus and anal dysplasia: Results of a pilot study using a STELLA computer simulation and economic model

OpenAIRE

Eli D. Ehrenpreis; Dylan G. Smith

2018-01-01

Background: Women with cervical cancer often have anal human papillomavirus (HPV) infection and anal dysplasia. However, effectiveness of anal HPV screening is unknown. Methods: A dynamic model was constructed using STELLA. Populations are represented as ''stocks'' that change according to model rates. Initial anal cytology in new cervical cancer patients, dysplasia progression and regression, cost of treating high-grade squamous intraepithelial lesions (HSIL), and lifetime costs for anal can...

Health-Related Quality of Life and Sexual Functioning of HIV-Positive Men Who Have Sex With Men Who Are Treated for Anal Intraepithelial Neoplasia

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Siegenbeek van Heukelom, Matthijs L.; Richel, Olivier; Nieuwkerk, Pythia T.; de Vries, Henry J. C.; Prins, Jan M.

2016-01-01

The impact of the treatment of precursor lesions of anal cancer (anal intraepithelial neoplasia) on health-related quality of life has not been investigated. This study aimed to evaluate the impact of 3 treatment options for anal intraepithelial neoplasia on health-related quality of life and sexual

CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

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Monica Molano

Full Text Available Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC are associated with human papillomavirus (HPV. Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS and laser capture microdissected (LCM tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

Risk Factors for the presence of anal intraepithelial neoplasia in HIV+ men who have sex with men

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Richel, Olivier; de Vries, Henry J. C.; Dijkgraaf, Marcel G. W.; van Noesel, Carel J. M.; Prins, Jan M.

2013-01-01

Anal Intraepithelial Neoplasia (AIN) is present in the majority of HIV+ men who have sex with men (MSM) and routine AIN-screening is subject of discussion. In this study we analysed a wide range of potential risk factors for AIN in order to target screening programs. We screened 311 HIV+ MSM by high

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

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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.

World wide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions.

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Washiya, Kiyotada; Takamizu, Ryuichi; Kumagai, Yukie; Himeji, Yukari; Kobayashi, Takako; Iwai, Muneo; Watanabe, Jun

2012-01-01

It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations. Copyright © 2012 S. Karger AG, Basel.

Comparison of the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low-grade and high-grade squamous intraepithelial lesions across different age groups.

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Paluszkiewicz, Aleksandra; Pruski, Dominik; Iwaniec, Kinga; Kędzia, Witold

2017-01-01

To assess the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low grade and high-grade squamous intraepithelial lesions across different age groups. The study included 1103 patients, age 25-70 years. All patients underwent in-depth diagnostic tests following either an abnormal Pap test result or a clinically suspicious cervical lesion. In all women the following examinations were performed: a molecular test detecting 14 high-risk types of HPV, a colposcopy examination, as well as directed-biopsy of the cervix. The studied population was subdivided into four age groups. It was observed that the percentage of high grade squamous intraepithelial lesions (HSIL) and cancers increased with women's age. Sensitivity of both methods for detecting high-grade squamous intraepithelial lesions was highest for women aged 40-49 years. Sensitivity values of HPV testing was higher than that of cervical cytology among women under age 50. Specificity of HPV testing increased significantly with age of women and was several fold higher across all age groups than the specificity of cervical cytology.

Manejo dos portadores das neoplasias intraepiteliais anais Managment of anal intra-epithelial neoplasia patients

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Sidney Roberto Nadal

2008-12-01

Full Text Available Acredita-se que a neoplasia intraepitelial anal (NIA, provocada pelo HPV, seja a lesão precursora do carcinoma anal. Segundo a literatura, são encontradas entre 11% e 52% dos homens infectados pelo HIV, entre 6% a 20% dos homens e 1% a 2,8% das mulheres sem essa infecção. Entre 8,5% e 13% das NIA de alto grau evoluirão para carcinoma invasivo, indicando a necessidade do rastreamento e do seguimento desses doentes para prevenção. Não há tratamento satisfatório com baixos índices de morbidez e a recidiva é comum. Em geral, as formas de tratamento podem de ser divididas em tópicas, entre elas, ácido tricloroacético, podofilina, podofilotoxina, imiquimod, terapia fotodinâmica, e ablativas, ou seja, excisão cirúrgica, ablação pelo LASER, coagulação pelo infravermelho e eletrofulguração. Há, ainda, os que consideram aceitável a conduta expectante. O tratamento tópico se justifica pelo caráter multifocal da lesão e os ablativos têm taxas de complicação e recidiva muito semelhantes. De qualquer forma, doentes com qualquer anormalidade histológica necessitam de seguimento adequado, principalmente com colposcopia e citologia anal.Anal intra-epithelial neoplasia (AIN, provoked by HPV, is considered as an anal cancer precursor. Some articles noticed that it occurred among 11% and 52% of men who have sex with men (MSM infected with HIV and, among seronegatives, from 6% to 20% of men and from 1% to 2.8% of women. From 8.5% to 13% of high grade AIN will evolve to invasive carcinoma, needing follow-up and screening for prevention. There is no satisfactory treatment with low morbidity and recurrence is frequent. There are two main forms of treatment: topics (trichloroacetic acid, podophylin, podophylotoxin, imiquimod, photodynamic therapy and ablatives (chirurgical excision, LASER, infrared, eletrocautery. Others consider acceptable an expectant management. Topical therapy is justified because of multifocal presentation of HPV

Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

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Brooke R Koltz

2013-01-01

Full Text Available Introduction: Automated screening of Thin Prep ® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep ® Imaging System (TIS. Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H and high-grade squamous intraepithelial lesion (HGSIL results on Thin Prep ® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07. The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study′s initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33% of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32% were interpreted as ASC-H and 164 (0.35% were interpreted as HGSIL. During the same time period automated screening (TIS was performed on 23,111 Pap tests. Interpretation of 62 (0.27% cases provided an ASC-H result, while 71 (0.31% were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71

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

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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.

HIV-associated anal cancer

OpenAIRE

Newsom-Davis, T; Bower, M

2010-01-01

HIV-associated anal carcinoma, a non-AIDS-defining cancer, is a human papillomavirus-associated malignancy with a spectrum of preinvasive changes. The standardized incidence ratio for anal cancer in patients with HIV/AIDS is 20-50. Algorithms for anal cancer screening include anal cytology followed by high-resolution anoscopy for those with abnormal findings. Outpatient topical treatments for anal intraepithelial neoplasia include infrared coagulation therapy, trichloroacetic acid, and imiqui...

Prevalence of anal cytological abnormalities in women with positive cervical cytology.

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Calore, Edenilson E; Giaccio, Claudia Maria Serafim; Nadal, Sidney R

2011-05-01

The objective of this study was to estimate the prevalence of cytological abnormalities of the anal mucosa in women with positive cervical cytology, but without macroscopic anal lesion. Ultimately we postulated if the anal mucosa may be a reservoir of HPV, which would allow the reinfection of cervix. Forty-nine patients with abnormal cervical cytology were selected for this work. In a period not exceeding one week of collecting cervix cytology, two swab specimens of the anal canal were also collected. Women diagnosed with cervical HSIL by Pap smear were referred for colposcopy with biopsy of the lesions, to confirm the cytologic diagnosis and ablation of the lesion. We demonstrated a high prevalence of anal squamous intraepithelial lesions in patients with cervical squamous intraepithelial lesions (29 of the total of 49 patients = 59.2%). Of the 20 cases of cervical LSIL, 11 (55%) had abnormal anal cytology. Of the 26 cases with cervical HSIL, 16 (61.5%) had abnormal anal cytology. So, there was a discrete higher prevalence of abnormal anal cytology in cases of high-grade cervical squamous lesions (cervical HSIL). These results help to support the hypothesis that the anal mucosa is a reservoir of HPV, which can be a source of re-infection for the cervix. However, there was no significant association between the practice of anal sex and the prevalence of anal cytological abnormalities. These facts are epidemiologically important for future programs for population eradication of cervical lesions related to HPV. Diagn. Cytopathol. 2011;39:323-327. © 2010 Wiley-Liss, Inc. Copyright © 2010 Wiley-Liss, Inc.

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis

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Caroline Alves de Oliveira

Full Text Available CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001 in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164, although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium

NARCIS (Netherlands)

Fleshner, N.E.; Kapusta, L.; Donnelly, B.; Tanguay, S.; Chin, J.; Hersey, K.; Farley, A.; Jansz, K.; Siemens, D.R.; Trpkov, K.; Lacombe, L.; Gleave, M.; Tu, D.; Parulekar, W.R.

2011-01-01

PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind

Environmental scan of anal cancer screening practices: worldwide survey results

International Nuclear Information System (INIS)

Patel, Jigisha; Salit, Irving E; Berry, Michael J; Pokomandy, Alexandra de; Nathan, Mayura; Fishman, Fred; Palefsky, Joel; Tinmouth, Jill

2014-01-01

Anal squamous cell carcinoma is rare in the general population but certain populations, such as persons with HIV, are at increased risk. High-risk populations can be screened for anal cancer using strategies similar to those used for cervical cancer. However, little is known about the use of such screening practices across jurisdictions. Data were collected using an online survey. Health care professionals currently providing anal cancer screening services were invited to complete the survey via email and/or fax. Information was collected on populations screened, services and treatments offered, and personnel. Over 300 invitations were sent; 82 providers from 80 clinics around the world completed the survey. Fourteen clinics have each examined more than 1000 patients. Over a third of clinics do not restrict access to screening; in the rest, eligibility is most commonly based on HIV status and abnormal anal cytology results. Fifty-three percent of clinics require abnormal anal cytology prior to performing high-resolution anoscopy (HRA) in asymptomatic patients. Almost all clinics offer both anal cytology and HRA. Internal high-grade anal intraepithelial neoplasia (AIN) is most often treated with infrared coagulation (61%), whereas external high-grade AIN is most commonly treated with imiquimod (49%). Most procedures are performed by physicians, followed by nurse practitioners. Our study is the first description of global anal cancer screening practices. Our findings may be used to inform practice and health policy in jurisdictions considering anal cancer screening

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

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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.

Diagnostic methods for prevention of anal cancer and characteristics of anal lesions caused by HPV in men with HIV/AIDS

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Araiz Cajueiro Carneiro Pereira

Full Text Available Abnormalities found with anuscopy under colposcopic vision, anal cytology and anal biopsy were evaluated in 21 men with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS at the Federal University of Pernambuco Hospital in Brazil. Mean age was 38.4 ± 6.0 years, and mean time of HIV infection was 8.3 ± 5.1 years; 95.2% of the patients had been on highly active antiretroviral therapy (HAART for an average of 6.6 ± 4.5 years. Mean CD4+ cell count was 482.2 ± 173.75 cells/mm³, and 80.9% presented a HIV viral load of < 5,000 copies/mL. Reported sexual preference was 52.4% homosexuals, 28.6% bisexuals, and 19.0%heterosexuals; 81% reported having had receptive anal intercourse and 61.9% reported more than 10 sexual partners of the same sex. Results of anuscopy under colposcopic vision revealed 17 (81.0% low-grade lesions and/or condylomata or micropapillae and four (19.0% high-grade lesions with or without condylomata. Among the 21 anal cytology examinations, seven (33.3% revealed low-grade squamous intraepithelial lesions (LSIL; three (14.3% presented atypical squamous cells of undetermined significance (ASCUS and 11 (52.4% were normal. Seventeen patients were submitted to anal biopsy with the following findings: three patients (17.6% with normal epithelium, one (5.9% with infection by HPV, three (17.6% with condylomatas, two (11.8% with AIN 1, four (23.6% with AIN 2, three (17.6% with AIN 3, and one (5.9% with PAIN 2. Anuscopy under colposcopic vision was found to be useful for detecting anal lesions and for guiding anal biopsies. Anal cytology was less useful, as it underestimated the frequency of lesions.

Association of Human Papillomavirus Infection and Abnormal Anal Cytology among HIV-Infected MSM in Beijing, China

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Zhang, Zhihui; Qian, Han-Zhu; Ruan, Yuhua; Zhou, Feng; Gao, Cong; Li, Mufei; Jin, Qi; Gao, Lei

2012-01-01

Background In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China. Methods HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes. Results Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04). Conclusions High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology. PMID:22558293

Association of human papillomavirus infection and abnormal anal cytology among HIV-infected MSM in Beijing, China.

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Yu Yang

Full Text Available BACKGROUND: In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM have been observed in China. Human papillomavirus (HPV infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China. METHODS: HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes. RESULTS: Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9% showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US in 19 (20.0%, atypical squamous cells but cannot exclude HSIL (ASC-H in 1 (1.1%, low-grade squamous intraepithelial lesion (LSIL in 15 (15.8%, and high-grade squamous intraepithelial lesion (HSIL in 1 (1.1%. HPV6 (20.0%, HPV16 (10.9%, HPV56 (10.9%, HPV52 (9.1% and HPV39 (9.1% were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%, HPV16 (19.4%, HPV45 (16.7%, HPV52 (16.7% and HPV18 (11.1%. In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04. CONCLUSIONS: High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology.

High grade squamous intraepithelial lesion in inmates from Ohio: cervical screening and biopsy follow-up

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Rofagha Soraya

2006-01-01

Full Text Available Abstract Background Cervical carcinoma remains the second leading cause of cancer death in women worldwide and sexual behavior is regarded as the main contributing factor. We studied cervical cytology screening with surgical biopsy follow-up in women prisoners and compared the findings to those in the general population. Methods We reviewed 1024 conventional cervical smears, 73 cervical biopsies and 2 loop electrosurgical excision procedure (LEEP specimens referred to us from the Correctional Center in Columbus, Ohio during a 12-month period. The results were compared to 40,993 Pap smears from the general population for the same 12-month period. Results High grade squamous intraepithelial lesion (HGSIL was diagnosed in 1.3% of the cervical smears from the inmate population versus 0.6% in the general population (p < 0.01. The unsatisfactory rate was 1.6% compared to 0.3% in the general population (p < 0.01. Among the study population, follow-up tissue diagnosis was obtained in 24.3% of the abnormal cytology results (ASCUS, LGSIL, and HGSIL. Of the HGSIL Pap smears, 61.5% had a subsequent tissue diagnosis. Thirty-nine biopsies (52% of the all inmate biopsies and LEEP showed CIN II/III (cervical intraepithelial neoplasia II/III. Eight of these thirty-nine follow-up biopsies diagnosed as CIN II/III had a previous cervical cytology diagnosis of ASCUS. The average age for HGSIL was 30.5 years (S.D. = 5.7 and for low grade squamous intraepithelial lesion (LGSIL was 27.2 years (S.D. = 6.1. Conclusion A significantly higher prevalence of HGSIL cervical cytology and unsatisfactory smears was encountered in female inmates, with tissue follow-up performed in less than two thirds of the patients with HGSIL. These results are in keeping with data available in the literature suggesting that the inmate population is high-risk and may be subject to less screening and tissue follow-up than the general population. Clinicians should proceed with urgency to improve

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

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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.

Human papillomavirus in anal biopsy tissues and liquid-based cytology samples of HIV-positive and HIV-negative Thai men who have sex with men

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Tippawan Pankam

2017-06-01

Full Text Available Background: Men who have sex with men (MSM are at high risk of developing human papillomavirus (HPV-related anal cancer. We compared HPV genotypes in anal tissues (Bx and anal liquid-based cytology fluid (LBC from HIV-positive and HIV-negative MSM. Methods: Bx (32 normal, 41 low-grade squamous intraepithelial lesions (LSIL and 22 high-grade squamous intraepithelial lesions (HSIL, along with LBC from the same visit, were selected from 61 HIV-positive and 34 HIV-negative MSM who enrolled into a prospective cohort in Bangkok, Thailand. HPV genotyping was performed on Bx and LBC. Results: Any HPV and high-risk HPV (HR-HPV prevalence were 63.2% and 60.0% in Bx and 71.6% and 62.1% in LBC, respectively. HIV-positive MSM had higher rates of HR-HPV genotypes detection (70.5% vs. 47.1%, p=0.03 in LBC than HIV-negative MSM. HPV16 (27% was the most common HR-HPV found in HSIL tissue. In HIV-positive MSM, the frequency of HR-HPV detection increased with histopathologic grading in both Bx and LBC samples. HSIL was associated with the presence of any HR-HPV(OR 7.6 (95%CI 1.8–31.9; P=0.006 in LBC and in Bx((OR 5.6 (95%CI 1.4–22.7; P=0.02. Conclusions: Our data strongly support the integration of HR-HPV screening on LBC samples, along with HPV vaccination, into an anal cancer prevention program. Keywords: Human papillomavirus, Anal tissues, Men who have sex with men, HIV, Thailand

Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection

DEFF Research Database (Denmark)

Jensen, Kirsten Egebjerg; Schmiedel, Sven; Frederiksen, Kirsten

2012-01-01

were also conducted. Hazard ratios (HRs) for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CIs) were calculated in the 2 groups. RESULTS: Among high-risk HPV positive women......BACKGROUND: Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. METHODS: In a population-based cohort study, 8,656 women underwent a structured interview......, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline (n=1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection...

Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial

NARCIS (Netherlands)

Richel, Olivier; de Vries, Henry J. C.; van Noesel, Carel J. M.; Dijkgraaf, Marcel. G. W.; Prins, Jan M.

2013-01-01

Anal cancer is an increasing issue in HIV-positive men who have sex with men (MSM). Screening for its precursor, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimum and have not been compared in a prospective trial. We compared efficacy and

Vulvær intraepithelial neoplasi

DEFF Research Database (Denmark)

Hansen, Signe Østergaard; Vorbeck, Christina Steen; Meinert, Mette

2018-01-01

Vulvar intraepithelial neoplasia Vulvar intraepithelial neoplasia (VIN) is a rare but premalig­nant condition. VIN has two aetiological pathways: a human papillomavirus (HPV)-dependent pathway, which is a vulvar high-grade squamous intraepithelial lesion (HSIL), and an HPV-independent pathway......, called differentiated VIN (d-VIN), associated with lichen sclerosus. d-VIN is more aggressive than vulvar HSIL. In case of symptoms, a biopsy should be performed. The recurrence risk is high: 25-50% regardless of treatment type. We recommend treatment with imiquimod as first choice to avoid mutilating...

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

Science.gov (United States)

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 (PHuman 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.

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

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Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

2004-08-01

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin

Preliminary results of a screening program for anal cancer and its precursors for HIV-infected men who have sex with men in Vigo-Spain

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Mauricio Iribarren-Díaz

Full Text Available Background and aims: Men who have sex with men (MSM infected with human immunodeficiency virus (HIV have the highest risk of developing anal cancer (AC. The objective of this study was to describe our screening implementation program in this population, and report the prevalence of human papillomavirus (HPV anal infection, and cytological and histological findings in a Spanish medium-size community (Vigo, Spain. Method: Prospective cohort analysis of 240 HIV-infected MSM. Cellular anal sample and high risk HPV (HR-HPV-tests were performed to study cytological changes and HPV genotyping. High resolution anoscopy (HRA was performed in 209 patients. Results were analyzed with respect to epidemiological, clinical and analytical factors. Results: Of 209 patients selected for HRA, the prevalence of HR-HPV anal infection, cytological and histological alterations was 85.6%, 47.5%, and 39.8%, respectively. Sensitivity and specificity for ≥ ASCUS (atypia of squamous cells of undetermined significance cytology in relation to histological alterations were 61% and 85%, (OR: 8.7; IC 95%: 4.4-17.2, respectively. Observed concordance between high-grade squamous intraepithelial lesion (HSIL cytology and HSIL anal intraepithelial neoplasia types 2 and 3 (AIN-2/3 histology was 64% (OR: 11.4; IC 95%: 3.6-36.7. One patient with HSIL cytology presented a prevalent anal squamous carcinoma. Conclusions: HRA was feasible with similar results to relevant groups. There was a high prevalence of anal HR-HPV infection, and cytological and histological alterations.

Fractal analysis of cervical intraepithelial neoplasia.

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Markus Fabrizii

Full Text Available INTRODUCTION: Cervical intraepithelial neoplasias (CIN represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed. METHODS: Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist's neoplasia grades with the predicted groups obtained by fractal methods. RESULTS: Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist's grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia. CONCLUSION: Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.

PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions.

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Wang, Zhen-Ming

2014-01-01

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

High-grade cervical intraepithelial neoplasia in human papillomavirus self-sampling of screening non-attenders

DEFF Research Database (Denmark)

Lam, J U H; Elfström, K M; Ejegod, D. M.

2018-01-01

precancer lesions. Here, we compare the cervical intraepithelial neoplasia grade 2 or worse (⩾CIN2) detection rate between non-attenders who participated in self-sampling and women attending routine screening. METHODS: A total of 23 632 women who were qualified as non-attenders in the Copenhagen Region were......BACKGROUND: Self-sampling for human papillomavirus (HPV) offered to women who do not participate in cervical cancer screening is an increasingly popular method to increase screening coverage. The rationale behind self-sampling is that unscreened women harbour a high proportion of undetected...... higher detection rates for ⩾CIN2 than routine cytology-based screening, and similar detection rates as HPV and cytology co-testing. This reinforces the importance of self-sampling for screening non-attenders in organised cervical cancer screening.British Journal of Cancer advance online publication, 14...

Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence

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Kjær, Susanne K; Frederiksen, Kirsten; Plum, Christian Edinger Munk

2010-01-01

Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection...

“Low-grade squamous intraepithelial lesion, cannot exclude high-grade:” TBS says “Don't Use It!” should I really stop it?

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Jeanine M Chiaffarano

2017-01-01

Full Text Available Background: The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs. Occasionally, Papanicolaou (Pap tests with evident low-grade SIL (LSIL also have some features suggestive but not diagnostic of high-grade SIL (HSIL. This study reviews our experience with “Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade” (LSIL-H and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. Methods: Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P ≤ 0.05. Results: There were a total of 1049 abnormal Paps with follow-up. High-grade dysplasia/carcinoma (HGD+ was found in 8% of LSIL, 30% of LSIL-H, 52% of atypical squamous cells (ASCs, cannot rule out HSIL (ASC-H, and 77% of HSIL Paps. The detection rate of HGD+ for LSIL-H was between that of LSIL (Pearson's Chi-square test, P = 0.000 and ASC-H (P = 0.04. If LSIL-H cases are reported as ASC-H, the rate of HGD+ for the ASC-H category would decrease from 51.5% to 37.4% (McNemar test, P = 0.000. Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7.7% to 10.4% (McNemar test, P = 0.000. Nearly 86.7% of LSIL-H cases were positive for high-risk HPV (HR-HPV in comparison to 77.5% of LSILs, 100% of ASC-Hs, and 75% of HSILs. The sample size for HR-HPV and LSIL-H was too small for meaningful statistical analysis. Conclusions: “LSIL-H” category detects more HGD+ than LSIL, and fewer than ASC-H and HSIL. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy

Anal HPV genotypes and related displasic lesions in Italian and foreign born high-risk males.

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Orlando, Giovanna; Beretta, Rosangela; Fasolo, M Michela; Amendola, Antonella; Bianchi, Silvia; Mazza, Francesca; Rizzardini, Giuliano; Tanzi, Elisabetta

2009-05-29

Anal intraepithelial neoplasia and anal cancer are closely related to infection from high-risk Human Papilloma Virus (HPV) genotypes. Since HPVs involved in disease progression are reported to vary by geographical regions, this study focuses on HPV genotypes spectrum in 289 males attending a Sexual Transmitted Diseases (STD) unit according to their nationality. Anal cytology, Digene Hybrid Capture Assay (HC2) and HPV genotyping were evaluated in 226 Italian (IT) and 63 foreign born (FB) subjects, recruited between January 2003 and December 2006. FB people were younger (median 32y-IQR 27-35 vs 36y-IQR 31-43, respectively; Mann-Whitney test por=atypical squamous cells of undetermined significance (ASCUS)) on anal cytology (95.0% vs 84.04%) (p=0.032; OR 3.61; 95% CI 1.04-1.23). HPV-16 is by far the most common genotype found in anal cytological samples independently from nationality while differences in distribution of other HPV genotypes were observed. The probability of infection from high-risk HPVs was higher in FB (OR 1.69; 95% CI 1.07-2.68) and is due to a higher rate of HPV-58 (OR 4.98; 95% CI 2.06-12.04), to a lower rate of HPV-11 (OR 0.35; 95% CI 0.16-0.77), to the presence of other high-risk genotypes (HPV-45, HPV-66, HPV-69). Multiple infections rate was high and comparable between IT and FB people. The relative contribution of each HPV genotype in the development of pre-neoplastic disease to an early age in the FB group cannot be argued by this study and more extensive epidemiological evaluations are needed to define the influence of each genotype and the association with the most prevalent high-risk HPVs on cytological intraepithelial lesions development.

Co-Testing of Cervical Screening Tests in Detection of High Grade Cervical Intraepithelial Neoplasia

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Smita Asthana

2017-10-01

Full Text Available Introduction: Co-testing performance for detection of high grade Cervical Intraepithelial Neoplasia (CIN has not been adequately addressed from Low Resource Countries (LRCs. Where isolated tests do not have adequate performance, further explorations are recommended. Aim: To evaluate the co-testing of conventional cervical screening tests such as Papanicolaou (Pap and Visual Inspection Cervix with Acetic Acid (VIA, with care HPV on Cervical Samples (CHPV or on Vaginal Samples (VHPV in the detection of high grade CIN. Materials and Methods: The cross-sectional study was conducted on ever married women of age 30 to 59 years in a rural community of Dadri. Women were screened by CHPV, VHPV, and Pap and VIA methods. Confirmation of screen positives was done by histology. Sensitivity, Specificity and likelihood ratios of different combinations of test determined to evaluate the performance. Results: Total eligible women, 66.2% (5032/7604 responded for screening. Analysis was performed on 4658, after excluding those who did not complete all screenings. Co-testing of CHPV (OR=246 or VHPV (OR=278 with Pap had highest association. Positive likelihood ratios of CHPV and VHPV with Pap in CIN II+ detection rates were 13.0 and 11.8 and in CIN III+ the detection rates were 18.0 and 16.0 respectively. Higher sensitivities and specificities were observed in co-testing for CIN III+ detection as against CIN II+ lesions. Conclusion: Choice of co-testing in a pair of tests for detection of high grade CIN is likely to depend on whether screening is targeted for developed or low resource country. VIA in isolation might not yield optimal results for LRCs.

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

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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.

Changes in the Extracellular Matrix Are Associated With the Development of Serous Tubal Intraepithelial Carcinoma Into High-Grade Serous Carcinoma.

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van der Steen, Sophieke C H A; Bulten, Johan; Van de Vijver, Koen K; van Kuppevelt, Toin H; Massuger, Leon F A G

2017-07-01

The identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of the main principles in cancer development and growth, but has been largely neglected in preinvasive lesions. This is the first study addressing the involvement of the ECM in the "step-by-step" transition of normal fallopian tube epithelium into preinvasive lesions, and eventually the progression of preinvasive lesions into invasive HGSC. The expression of highly sulfated chondroitin sulfate (CS-E), a characteristic glycosaminoglycan of the cancer-associated ECM, was assessed by immunohistochemistry in a large cohort of precursor lesions of the full spectrum of HGSC development, including 97 serous tubal intraepithelial carcinomas (STICs), 27 serous tubal intraepithelial lesions, and 24 p53 signatures. In addition, the immunological reactivity in the microenvironment was evaluated. Increased stromal expression of highly sulfated CS-E was observed in 3.7%, 57.7%, and 90.6% of serous tubal intraepithelial lesions, STICs, and invasive HGSCs, respectively (P STIC, P STIC and paired HGSC was demonstrated. Intense stromal CS-E expression in STIC was significantly associated with an immune infiltrate (P < 0.001). Our study showed that increased stromal CS-E expression is related to the degree of the tubal epithelium abnormality. Specific alterations in the ECM (ie, CS-E expression) occur early in pelvic HGSC development and may represent a novel biomarker of early cancer progression, useful for the identification of novel clinical strategies.

Prevalence of high-grade squamous intraepithelial lesions and cervical cancer among patients with unsatisfactory colposcopic examination, without visible lesion

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Fernanda Rangel da Veiga

Full Text Available CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL, the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment. DESIGN AND SETTING: Cross-sectional study in Colposcopy Clinic of IFF/Fiocruz. METHOD: Patients admitted between December 1989 and April 2007 with cytological diagnoses of HSIL but with unsatisfactory colposcopic examinations without visible lesions underwent cervical cone biopsy. RESULTS: Sixty-five such patients were included, comprising 33.8% with HSIL and 4.6% with cancer, confirmed histologically. The other patients presented low-grade squamous intraepithelial lesion (26.1%, glandular dysplasia (1.5% and absence of disease (33.8%. CONCLUSION: The observed prevalence of cancer and HSIL does not seem to be enough to justify immediate referral for cone biopsies to investigate the cervical canal in these cases. The findings suggest that the recommendation of repeated cytological tests following an initial one with HSIL, among patients with unsatisfactory colposcopic examinations without visible lesions, is appropriate in our setting. Efforts are needed to ensure adherence to follow-up protocols in order to reduce the chances of losses.

HPV type-related chromosomal profiles in high-grade cervical intraepithelial neoplasia

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Bierkens Mariska

2012-01-01

Full Text Available Abstract Background The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3] result from a persistent infection with high-risk human papillomavirus (hrHPV types and the accumulation of (epigenetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. Methods Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (≥ 5 years. Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. Results Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31 in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR Conclusions Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is

Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.

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Correnti, Maria; Medina, Francisco; Cavazza, María Eugenia; Rennola, Antonieta; Avila, Maira; Fernándes, Andreína

2011-06-01

Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women. Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections. HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31. Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela. Copyright © 2011 Elsevier Inc. All rights reserved.

High prevalence and incidence of HPV-related anal cancer precursor lesions in HIV-positive women in the late HAART era.

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Hidalgo-Tenorio, Carmen; de Jesus, Samantha E; Esquivias, Javier; Pasquau, Juan

2017-12-02

Anal cancer is one of the most common non-AIDS defining malignancies, especially in men who have sex with men and women living with HIV (WLHIV). To evaluate the prevalence and incidence of precursor lesions (high-grade squamous intraepithelial lesions [HSIL]) and anal cancer in our cohort of women and to compare them to cervical lesions; to calculate the percentage of patients that acquire and clear oncogenic genotypes (HR-HPV) in the anal canal; and to determine predictive factors for anal HPV infection. Prospective-longitudinal study (May 2012-December 2016). At baseline (V1) and follow up visits, anal mucosa samples were taken in liquid medium for cytology and HPV PCR. In cases of abnormal anal cytology and/or positive HR-HPV PCR results, a high resolution anoscopy was performed. Patients were also referred to the gynaecologist. Ninety five women with an average age of 43.7years were included. At baseline, 11.6% had cervical abnormalities (4.1% CIN1, 2.2% CIN2/3, 1.1% cervical cancer), 64.3% anal abnormalities (50% LSIL/AIN1, 9.5% HSIL/AIN2/3 and 2.4% anal cancer) and 49.4% had HR-HPV genotypes. During 36months of follow up, the incidence of anal HSIL was 16×1,000 person-years; 14.8% acquired HR-HPV genotypes and 51.2% cleared them, P=.007. No patients presented CIN1/2/3/ or cervical cancer. In the multivariate analysis we found the following predictive factors for HR-HPV infection: smoking (RR: 1.55, 95%CI: 0.99-2.42), number of sexual partners >3 (RR: 1.69; 95%CI: 1.09-2.62), cervical and anal dysplasia (RR: 1.83; 95%CI: 1.26-2.67) and (RR: 1.55; 95%CI: 1.021-2.35), respectively. Despite clearance rates of anal oncogenic genotypes being higher than acquisition rates, prevalence and incidence of HSIL were still high and greater than cervical HSIL. Therefore, screening for these lesions should perhaps be offered to all WLHIV. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights

Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

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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.

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma.

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Ducie, Jennifer; Dao, Fanny; Considine, Michael; Olvera, Narciso; Shaw, Patricia A; Kurman, Robert J; Shih, Ie-Ming; Soslow, Robert A; Cope, Leslie; Levine, Douglas A

2017-10-17

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.

Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H) cannot be ruled out.

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Cytryn, Andréa; Russomano, Fábio Bastos; Camargo, Maria José de; Zardo, Lucília Maria Gama; Horta, Nilza Maria Sobral Rebelo; Fonseca, Rachel de Carvalho Silveira de Paula; Tristão, Maria Aparecida; Monteiro, Aparecida Cristina Sampaio

2009-09-01

The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

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Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

2010-01-01

To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).......To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

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Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

Diagnóstico de HPV anal em mulheres com NIC: prevenção de câncer do ânus? Anal HPV diagnosis in women with NIC: anal cancer prevention?

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Alice Capobiango

2009-12-01

Full Text Available Os objetivos deste estudo foram avaliar a frequência de HPV anal em pacientes com neoplasia intraepitelial cervical (NIC, verificar a concordância entre os subtipos encontrados nos dois locais e investigar os fatores que influenciaram a ocorrência de HPV anal em mulheres com NIC sem evidências clínicas de imunodepressão. Foram avaliadas 52 mulheres com idades entre 16 e 72 anos e diagnóstico de neoplasia intraepitelial cervical graus I, II e III. A identificação do DNA (ácido desoxirribonucleico do HPV e de sete subtipos dos vírus foi realizada por meio da reação em cadeia da polimerase (PCR em material colhido no ânus e colo uterino. Foram pesquisados fatores que poderiam contribuir para a infecção anal, como paridade, número de parceiros, tabagismo, manipulação e coito anal e o tipo de doença ginecológica. Das 52 mulheres, foi diagnosticado HPV na região anal em 25 (48%, das quais 23 (44% também apresentavam HPV no colo uterino - resultado significativo para existência do HPV em portadoras de NIC. Em 16 (31% o HPV foi diagnosticado somente no colo uterino e em 11 (21% não foi identificado em colo ou ânus. Houve associação significativa nas variáveis paridade (p=0,02 e número de parceiros (p=0,04. Concluiu-se que: as mulheres com HPV genital têm mais probabilidade de serem acometidas por HPV anal; não há concordância unânime entre os subtipos do HPV do colo do útero e do ânus e a paridade e o número de parceiros contribuem para aumentar a incidência de HPV anal nas mulheres sem imunodeficiência e com HPV cervical.This study aims were to assess the frequency of HPV anal infection in patients with cervical intra-epithelial neoplasia (CIN, to find out the relation between the found subtypes, when present in both regions, and investigate factors that influenced the occurrence of anal HPV in women with CIN. Fifty two women with age between 16 and 72 years and cervical intra-epithelial neoplasia (CIN diagnosis

Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics.

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Gross, Amy L; Kurman, Robert J; Vang, Russell; Shih, Ie-Ming; Visvanathan, Kala

2010-01-01

The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).

Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

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Amy L. Gross

2010-01-01

Full Text Available The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC, particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs but our own findings (unpublished data and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs.

Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H cannot be ruled out

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Andréa Cytryn

Full Text Available CONTEXT AND OBJECTIVE: The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS into ASC-US (undetermined significance and ASC-H (high-grade intraepithelial lesion cannot be ruled out. The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF with ASC-H cytology, and compare them with ASC-US cases. DESIGN AND SETTING: Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. METHODS: ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis was taken as the gold standard. RESULTS: The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55% and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764. Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83; P = 0.2786998. There were no uterine cervical cancer cases. CONCLUSION: The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

High-grade squamous intraepithelial lesion (HSIL) of the cervix with bizarre cytological appearances ('pleomorphic HSIL'): a review of 19 cases.

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Stewart, Colin J R

2017-08-01

Cervical high-grade squamous intraepithelial lesions (HSILs) are typically characterised by a proliferation of immature basaloid cells with relatively uniform hyperchromatic nuclei. In this report we describe 19 cases of HSIL exhibiting focal but very marked nuclear atypia often associated with multinucleation ('pleomorphic HSIL'). The bizarre cytological changes mainly involved the basal epithelium particularly in endocervical crypts where the neoplastic cells undermined the native glandular epithelial cells. Superficially invasive squamous cell carcinoma (SISCCA) was present in three cases (16%) and while this was more common than in a comparative series of 40 'conventional' HSIL excision specimens (5%), the difference was not statistically significant. All three invasive cases demonstrated additional histological features that have been associated with increased risk of SISCAA (expansile crypt involvement by HSIL, luminal necrosis, and/or intraepithelial squamous maturation), and the invasive foci were associated microanatomically with conventional-type rather than pleomorphic HSIL. The bizarre cells expressed p16 and p63 proteins but usually lacked mitotic activity and showed less Ki-67 labelling than adjacent conventional HSIL. These findings suggest that pleomorphic epithelial changes in HSIL do not necessarily indicate more aggressive biological behaviour and may, in some cases, represent a degenerative phenomenon. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

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

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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.

Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including Rsf-1 (HBXAP), cyclin E and fatty acid synthase.

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Sehdev, Ann Smith; Kurman, Robert J; Kuhn, Elisabetta; Shih, Ie-Ming

2010-06-01

Serous tubal intraepithelial carcinoma (STIC) has been proposed as a precursor for many pelvic high-grade serous carcinomas. Our previous analysis of the ovarian cancer genome identified several genes with oncogenic potential that are amplified and/or overexpressed in the majority of high-grade serous carcinomas. Determining whether these genes are upregulated in STICs is important in further elucidating the relationship of STICs to high-grade serous carcinomas and is fundamental in understanding the molecular pathogenesis of high-grade serous carcinomas. In this study, 37 morphologically defined STICs were obtained from 23 patients with stage IIIC/IV high-grade serous carcinomas. Both STICs and the high-grade serous carcinomas were analyzed for expression of Rsf-1 (HBXAP), cyclin E, fatty acid synthase (FASN) and mucin-4. In addition, they were examined for expression of established markers including p53, Ki-67 and p16. We found that diffuse nuclear p53 and p16 immunoreactivity was observed in 27 (75%) of 36 and 18 (55%) of 33 STICs, respectively, whereas an elevated Ki-67 labeling index (>or=10%) was detected in 29 (78%) of 37 STICs. Cyclin E nuclear staining was seen in 24 (77%) of 35 STICs, whereas normal tubal epithelial cells were all negative. Increased Rsf-1 and FASN immunoreactivity occurred in 63%, and 62% of STICs, respectively, compared with adjacent normal-appearing tubal epithelium. Interestingly, only one STIC showed increased mucin-4 immunoreactivity. Carcinomas, when compared with STICs, overexpressed p16, Rsf-1, cyclin E and FASN in a higher proportion of cases. In conclusion, STICs express several markers including Rsf-1, cyclin E and FASN in high-grade serous carcinomas. In contrast, mucin-4 immunoreactivity either did not change or was reduced in most STICs. These results suggest that overexpression of Rsf-1, cyclin E and FASN occurs early in tumor progression.

Indicação da anuscopia de alta resolução e citologia anal na prevenção de HPV e câncer colorretal em pacientes portadores de HIV Indication of high resolution anoscopy and anal cytology for prevention of HPV and colorectal cancer in HIV patients

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Hugo Leonardo Madeiro Arcanjo Silva

2010-12-01

analysis. RESULTS: We found 22 males and 9 females between 20 and 67 years. Of the 31 tested, 4 were in stage of immunosuppression, 23 were using antiretroviral therapy, 16 with history of receptive anal sex and 12 with a history of condyloma acuminata. In the HRA 11 patients had changes and 7 were confirmed by cytology. We also verified eight patients with abnormal cytology who had no changes to the HRA. In the atypical squamous cells of undetermined significance (Ascus cytology had three, five with parakeratosis and/or hyperkeratosis, six intraepithelial lesions and a low grade squamous intraepithelial lesion high grade. CONCLUSION: We suggest the use of anoscopy high resolution combined with anal cytology for screening in patients with the HIV, since these examinations are complementary for the detection of lesions that are related to anorectal cancer.

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

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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 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.

Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis.

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Kuhn, Elisabetta; Meeker, Alan; Wang, Tian-Li; Sehdev, Ann Smith; Kurman, Robert J; Shih, Ie-Ming

2010-06-01

Short telomeres are one of the main genetic manifestations in human cancer, as they have been shown to play an important role in inducing chromosomal instability and in contributing to tumor progression. The purpose of this study was to determine if changes in telomere length occur in serous tubal intraepithelial carcinoma (STIC), the putative precursor of "ovarian" high-grade serous carcinoma (HGSC). Twenty-two STICs from 15 patients with concurrent but discrete HGSCs were analyzed for telomere length on formalin-fixed, paraffin-embedded sections by conducting p53 immunofluorescence to assist in identifying STICs and telomere-specific FISH. Telomere length (short, long, or no change) in STICs was compared with HGSCs using normal fallopian tube epithelium and stromal cells as controls. We found that STICs had the shortest telomeres, as 18 (82%) of 22 STICs had short telomeres, whereas only 2 (9%) showed no change and 2 (9%) had long telomeres compared with the normal-looking tubal epithelium. In contrast, among 12 paired HGSCs and STICs, 6 HGSCs showed an increase in telomere length, one showed a decrease in length and 5 did not show any change when compared with their matched STICs, although, such as STICs, the majority of HGSCs had shorter telomeres than the associated normal tubal epithelial cells. These differences in telomere length between normal tubal epithelial cells and STICs, and between STICs and HGSCs were statisticaly significant (PSTICs provides further support to the proposal that STICs are precursors of HGSC and opens new areas of research in elucidating the early events of ovarian high-grade serous carcinogenesis.

Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

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Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf

2013-01-01

Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination...... on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical...... higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both...

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests

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Flávia de Miranda Corrêa

Full Text Available CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid test for triage of low-grade squamous intraepithelial lesions (LSIL requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3, in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%. The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS, was available in two studies (33% and 90.8%; and specificity was available in one study (53%. CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

Perceived cervical cancer risk among women treated for high-grade cervical intraepithelial neoplasia: The importance of specific knowledge.

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Sonia Andersson

Full Text Available Women with high-grade cervical intraepithelial neoplasia (CIN are at increased risk for developing cervical cancer. We examine how women with high-grade CIN perceive their own risk, and about pertinent knowledge concerning human high-risk papillomavirus (HPV, CIN and cervical cancer.All patients who underwent first-time treatment of high-grade CIN (grade 2+ were followed-up at 6-months at the Karolinska University Hospital, Stockholm, Sweden and were invited to participate in the present study. This included completion of a questionnaire examining sociodemographic characteristics, self-perceived risk of cervical cancer without regular gynecologic follow-up, and 14 queries about HPV, CIN and cervical cancer knowledge, inter alia.The participation rate was 96.6%, with 479 women enrolled in this study. Over 75% were age 40 or younger, over half had completed university education. Most were married or co-living with their partner and were gainfully employed. On a scale scored from 10 (highest self-perceived risk of cervical cancer without regular gynecologic follow-up to 1 (lowest self-perceived risk, 64% rated their risk ≥ 7; almost 30% viewed their risk ≤ 6 and 7.5% did not rate their risk. A Specific Knowledge Scale with six of the queries explained 58.3% of the total variance. Nearly 30% of the women answered four or fewer of the six queries correctly. The Specific Knowledge Scale predicted self-perceived cervical cancer risk (Odds ratio = 11.3, 95% Confidence Interval 5.6 - 22.6 after adjusting for age, income and education. Most of the women with low self-perceived cervical cancer risk did not rate their HPV-related knowledge as good. However, 32 predominantly university-educated women, with low self-perceived cervical cancer risk, considered their HPV-related knowledge good.It is vital to effectively convey accurate information about these patients' cervical cancer risk, needed preventive and follow-up measures, together with the relevant

HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade

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Evans, Mark F.; Peng, Zhihua; Clark, Kelli M.; Adamson, Christine S.-C.; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

2014-01-01

Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: PHPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay’s high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when ‘LSIL vs. HSIL’ assignment is

Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial.

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Richel, Olivier; de Vries, Henry J C; van Noesel, Carel J M; Dijkgraaf, Marcel G W; Prins, Jan M

2013-04-01

Anal cancer is an increasing issue in HIV-positive men who have sex with men (MSM). Screening for its precursor, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimum and have not been compared in a prospective trial. We compared efficacy and side-effects of imiquimod, topical fluorouracil, and electrocautery for the treatment of AIN. In this open-label randomised trial, we included HIV-positive MSM older than 18 years visiting the HIV outpatient clinic of the Academic Medical Center, Amsterdam, Netherlands. Patients with histologically confirmed AIN were randomly assigned to receive either 16 weeks of imiquimod (three times a week), 16 weeks of topical fluorouracil (twice a week), or monthly electrocautery for 4 months. Randomisation was done with random block sizes of three and six, stratified for AIN grade (AIN grades 1, 2, or 3) and AIN location (peri-anal or intra-anal). Participants were assessed by high-resolution anoscopy 4 weeks after treatment. Responding patients returned for follow-up 24 weeks, 48 weeks, and 72 weeks after treatment. The primary endpoint was histological resolution of AIN measured 4 weeks after treatment and AIN recurrence at week 24, week 48, and week 72 after treatment. The primary analysis was done in a modified intention-to-treat population, including all patients who had received their assigned treatment at least once. The trial is registered at the Netherlands Trial Register, number NTR1236. Between Aug 12, 2008, and Dec 1, 2010, we screened 388 HIV-positive MSM for AIN by high resolution anoscopy. Of the 246 (63%) patients who had AIN, 156 (63%) were randomly assigned to either receive imiquimod (54 patients), topical fluorouracil (48 patients), or electrocautery (46 patients) following withdrawing of consent by eight patients. Modified intention-to-treat analysis showed a complete response in 13 (24%, 95% CI 15-37) patients in the imiquimod group, eight (17%, 8-30) of patients

Serous tubal intraepithelial neoplasia: the concept and its application.

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Meserve, Emily E K; Brouwer, Jan; Crum, Christopher P

2017-05-01

In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that include both serous tubal epithelial proliferations (or lesions) of uncertain significance and serous tubal intraepithelial carcinomas. These precursors can be considered from three perspectives. The first is biologic underpinnings, which are multifactorial, and include the intersection of DNA damage with Tp53 mutations and disturbances in transcriptional regulation that increase with age. The second perspective is the morphologic discovery and classification of intraepithelial neoplasms that are intercepted early in their natural history, either incidentally or in risk-reduction surgeries for germline mutations. For the practicing pathologist, as well as the investigators, a distinction between a primary intraepithelial neoplasm and an intramucosal carcinoma must be made to avoid misinterpreting (or underestimating) the significance of these proliferations. The third perspective is the application of this information to intervention, devising strategies that will actually lower the ovarian cancer death rate by opportunistic salpingectomy, widespread comprehensive genetic screening and early detection. Central to this issue are the questions of (1) whether some STICs are metastatic, (2) whether lower-grade epithelial proliferations can invade prior to evolving into intraepithelial carcinoma, or (3) metastasize and become malignant elsewhere ('precursor escape'). An important caveat is the persistent and unsettling reality that many high-grade serous carcinomas are not associated with an obvious point of initiation in the fallopian tube. The pathologist sits squarely in the midst of all of these issues, and has a pivotal role in managing expectations for stemming the death

Serous tubal intraepithelial carcinoma localizes to the tubal-peritoneal junction: a pivotal clue to the site of origin of extrauterine high-grade serous carcinoma (ovarian cancer).

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Seidman, Jeffrey D

2015-03-01

Recent data suggest that intraepithelial carcinoma of the fallopian tube [serous tubal intraepithelial carcinoma (STIC)] is the precursor of high-grade extrauterine serous carcinoma. A more specific location for the origin of this lesion is suggested by the recently described junction between the fallopian tubal epithelium and the peritoneum [tubal-peritoneal junction (TPJ)]. Fallopian tubes from 202 patients with advanced-stage high-grade extrauterine serous carcinoma or carcinosarcoma were evaluated histologically as were 124 prophylactic salpingo-oophorectomy specimens. These included 54 patients with BRCA or other high-risk mutation or a family history of BRCA mutation and 70 with a personal or family history of breast carcinoma. STIC was found in 81 of 202 patients with serous carcinoma (40.1%). STIC was present in 73 of 141 (52%) cases in which the fimbriae were present and in 62 of 100 (62%) cases in which the TPJ was present (P not significant). In comparison with these groups, when fimbriae and TPJ were absent, STIC was found in 8 of 61 (13%) cases (PSTIC. The mean size of STIC was 1.7 mm. In 32 cases (39.5%), the lesion was flat and in 49 (60.5%), papillary. The mean size of flat STICs was 0.8 mm as compared with 2.3 mm for papillary STICs (P=0.00005). STIC was identified in the same tissue fragment as the junction in 48 cases. The mean distance of STIC to the junction was 1.8 mm. In 11 cases, STIC was flanked by peritoneal mesothelium on one side and tubal epithelium on the opposite side. In 51 patients, the mean distance of invasive carcinoma from the TPJ was 1.8 mm. This distance was 1.9 mm when STIC was present (37 cases) in comparison with 1.5 mm when STIC was absent (14 cases) (P not significant). In 27 of 42 cases (64%), STIC was contiguous with invasive carcinoma. Lamina propria invasion was present in 71% of cases in which STIC was present as compared with 26% of cases in which STIC was absent (PSTIC was present as compared with 26% of cases in

Radiation therapy of recurrent anal squamous cell carcinoma in-situ: a case report

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Noone Robert

2010-02-01

Full Text Available Abstract Introduction High-grade anal intraepithelial neoplasia, also referred to as anal squamous carcinoma in-situ, or Bowen's disease of the anus, make up less than 1% of all digestive system cancers in the United States. The treatment of choice is surgical resection with anal mapping. However, this disease often recurs or persists, requiring additional surgery for these patients. This can compromise the anal sphincter leading to leakage. In this case report, we discuss the efficacy of radiation therapy as a modality to treat post-excisional recurrent Bowen's disease, which may prevent sphincter compromise, leading to improved quality of life. Case presentation An 84-year-old Caucasian woman presented with post-excisional persistent/recurrent squamous cell carcinoma in-situ. The initial lesion measured 3 cm in diameter on the right lateral side of the anal margin. A standard surgery consisting of wide local excision with anal mapping was performed. The margins were clear and our patient was followed up. Our patient recurred with a 1.2 × 0.8 cm lesion on the left anal verge extending to the anal canal. A biopsy along with mapping was done, and 2 of the 17 mapping specimens were positive for carcinoma in-situ, one in the anal canal. Due to the location of the positive anal mapping, and in order to prevent sphincter compromise on re-excision, our patient was offered definitive radiation therapy. Two years after radiation therapy, our patient showed no signs of recurrent disease and had good sphincter control. Conclusion Although the main treatment modality for treating persistent/recurrent Bowen's disease is surgery, an alternative approach using external beam radiation for CIS may be enough to provide a cure for some patients with recurrent disease.

Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

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Arbyn, Marc; Buntinx, Frank; Van Ranst, Marc; Paraskevaidis, Evangelos; Martin-Hirsch, Pierre; Dillner, Joakim

2004-02-18

The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II

Immunocytoexpression profile of ProExC in smears interpreted as ASC-US, ASC-H, and cervical intraepithelial lesion

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Zeynep Tosuner

2017-01-01

Full Text Available Aims: We aimed to investigate the immunocytoexpression profiles of a novel assay ProEx C for topoisomerase II alpha (TOP2A and minichromosome maintenance protein 2 (MCM2 in abnormal interpreted smears. Settings and Design: Screening programs with Papanicolaou smear and high risk group human papilloma virus testing have yielded a dramatic reduction of cervical cancer incidence. However, both of these tests have limited specificity for the detection of clinically significant cervical high grade lesions. ProEx C for topoisomerase II alpha (TOP2A and minichromosome maintenance protein 2 (MCM2 has been considered to have tight association with high grade intraepithelial lesions. Materials and Methods: A total number of 54 SurePath cervical cytology specimens of patients previously interpreted as atypical squamous cells-undetermined significance (ASC-US, atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H, low grade squamous intraepithelial lesion (LSIL, and high grade squamous intraepithelial lesion (HSIL were included in our study. Results and Conclusions: ProEx C was positive in 14 of HSILs (100%, 3 of 19 LSILs (16%, 2 of 4 ASC-Hs, and none of ASC-USs (0%. The ProEx C test showed very intense nuclear staining in all cytologically abnormal cells. Further studies are indicated to evaluate the diagnostic role of ProEx C.

HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.

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Mark F Evans

Full Text Available Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3 based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL. In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH. Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4, and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3% CIN 1, 22/22 (100% CIN 2 and in 32/32 (100% CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7% showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5% by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001. These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e

Rastreamento e seguimento dos portadores das lesões anais induzidas pelo papilomavírus humano como prevenção do carcinoma anal Screening and follow-up of patients with anal HPV induced lesions for anal carcinoma prevention

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Sidney Roberto Nadal

2009-06-01

Full Text Available O Papilomavírus humano (HPV é o agente sexualmente transmissível mais comum na região perianal. O vírus provoca lesões clínicas e subclínicas que podem evoluir para carcinoma anal. É descrito o aumento da incidência desse tipo de tumor naqueles que praticam sexo anal; nos portadores, de ambos os sexos, de lesões genitais HPV induzidas; nas pessoas com neoplasias intraepiteliais anais de alto grau, o precursor do carcinoma, com maior incidência nos infectados pelo vírus da imunodeficiência humana (HIV, e com outras causas de supressão imunológica. Outra característica das lesões HPV induzidas é a elevada incidência de recidivas. Daí, a importância do seguimento por longo prazo e da pesquisa de meios terapêuticos para reduzir essa ocorrência. A possibilidade da detecção das lesões precursoras indica que programas padronizados de rastreamento para a prevenção do câncer anal deveriam ser instituídos. Os esfregaços anais para citologia vêm sendo realizados, com eficácia semelhante a das coletas cervicais e a colposcopia anal tem sido indicada para biópsias dirigidas quando a citologia mostrou-se alterada, embora muitos recomendam-na, também, como método de rastreamento. Nesse artigo, descrevemos a padronização da coleta de material para citologia anal e o método de realização da colposcopia anal, bem como a periodicidade com que devem ser repetidos.The human papillomavirus is the most frequent sexually transmitted agent in anorectal area. This virus provokes clinical and sub-clinical lesions that can evolve to anal carcinoma. Its incidence is increasing among those who practice anal receptive sex; in both gender patients with genital HPV induced lesions; in those with high grade anal intra-epithelial neoplasia, anal carcinoma precursor, mainly among HIV infected persons or with other causes of immunodeficiency. Another HPV induced lesions characteristic is their elevated incidence of recurrences. Therefore

Unsatisfactory exfoliative anal cytology samples, 15-year experience with histologic, cytologic, and molecular follow-up.

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Khattab, Ruba; McMeekin, Emily; Taege, Alan J; Hekman, James M; Brainard, Jennifer A; Underwood, Dawn; Procop, Gary W; Sturgis, Charles D

2018-02-01

The incidence of anal carcinoma has risen in recent decades. Exfoliative cytology screening of selected high risk patients is performed in many centers. Unsatisfactory cytology results are frustrating to patients, clinicians, and laboratorians. The aim of this study is to ascertain outcomes of patients with non-diagnostic anal cytology. A retrospective review of anal cytology testing performed at the Cleveland Clinic between 01/01/2001 and 12/31/2015 was performed. All cases were received as liquid-based samples and processed as ThinPreps (Hologic, Marlborough, MA). Co-testing for HR-HPV DNA was performed using Hybrid Capture 2® (Qiagen, Germantown, MD) in the majority of patients. Of 1,276 ThinPrep anal cytology samples, 130 (10%) were deemed unsatisfactory. 77% of patients were HIV positive. 85% were males. Of the unsatisfactory cases, 116 (89%) were co-tested for HR-HPV DNA. Of those, 40 patients (34%) had a simultaneous positive HR-HPV DNA. Adequate follow up cytology within a one year and a two year period revealed that 18/130 (14%) and 26/130 (20%) of patients had ASC or SIL respectively. Histologic follow-up within one and two years showed 3 patients (2%) and 8 patients (6%) with HSIL or worse. High risk patients with unsatisfactory anal cytology are not "negative". At least one-third proved to be concomitantly HR-HPV DNA positive with one-fifth showing subsequent cytologic squamous abnormalities and with more than 5% being diagnosed with a high grade intraepithelial lesion within two years. Prompt repeat cytology and/or HR-HPV DNA is recommended for high risk patients with non-diagnostic cytology. © 2017 Wiley Periodicals, Inc.

Analytic and clinical performance of cobas HPV testing in anal specimens from HIV-positive men who have sex with men.

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Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V; Chen, Jie; Lorey, Thomas S; Gage, Julia C; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M; Castle, Philip E

2014-08-01

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Prevalence status and association with human papilloma virus of anal squamous proliferative lesions in a patient sample in Taiwan.

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Tsai, Tsen-Fang; Kuo, Guan-Tin; Kuo, Lu-Ting; Hsiao, Cheng-Hsiang

2008-08-01

Anal squamous proliferative lesions, including condyloma, anal high-grade squamous intraepithelial lesion (AHSIL) and squamous cell carcinoma (SCC), are associated with human papilloma virus (HPV) infection. The objectives of the study were to investigate the HPV prevalence of anal squamous proliferative lesion in Taiwan. From 1991 to 2005, 41 cases with condyloma, 12 cases with AHSIL, and 13 cases with SCC were collected. DNA was extracted from the tissue sections of these patients, and the HPV genotype was identified using polymerase chain reaction and gene chip. The integration status of HPV16 DNA was also evaluated by quantitative real-time polymerase chain reaction. Anal condyloma mainly occurred in young males, but AHSIL and anal SCC developed in older patients. In the patients with human immunodeficiency virus (HIV) infection, AHSIL developed much earlier than patients without HIV infection (36 vs. 61 years). HPV DNA was detected in all 56 patients whose specimens contained adequate DNA. High-risk HPVs (type 16, 58, etc.) were mainly detected in the AHSIL and SCC. Multiple HPV infection was found in AHSIL (4 of 12) and condyloma (11 of 34) but was rare in invasive cancer (1 of 12). Seven of 8 patients with HPV16 infection had coexistent episomal and integrated forms. HPV58 is a unique high-risk HPV prevalent in Taiwan. The integration status of HPV seems not correlated with the severity of the dysplasia. In our study, emerging HIV-positive AHSIL in recent years indicates that we should devote more efforts to promote sexual safety among the people who engaged in anal intercourse.

Less medical intervention after sharp demarcation of grade 1-2 cervical intraepithelial neoplasia smears by neural network screening

NARCIS (Netherlands)

Kok, MR; Boon, ME; Schreiner-Kok, PG; Hermans, J; Grobbee, DE; Kok, LP

2001-01-01

BACKGROUND. Neural network technology has been used for the daily screening of cervical smears in The Netherlands since 1992. The authors believe this method might have the potential to demarcate diagnoses of Grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). METHODS. Of 133,196 women who were

Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3.

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Hannah P Yang

Full Text Available Cervical intraepithelial neoplasia grade 3 (CIN3, the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.CIN3 cases varied substantially by size (1-10 LEEP segments and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.

Cervical squamous and glandular intraepithelial neoplasia: identification and current management approaches Neoplasia intraepitelial cervical escamosa y glandular: identificación y estrategias de manejo

OpenAIRE

V Cecil Wright

2003-01-01

Certain types of human papillomaviruses (HPV) are associated with squamous intraepithelial lesions and cancer and these are termed high-risk. HPV type 16 is detected in approximately half of the high-grade squamous intraepithelial lesions and cancer. Because of the high rate of spontaneous regression of low-grade squamous lesions, follow-up by cytology, colposcopy and possible biopsy appears preferable. Due to the higher rate of progression to malignancy of the high-grade lesions conservative...

Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

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Lehtinen, Matti; Ault, Kevin A; Lyytikainen, Erika

2011-01-01

High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined....

Serous tubal intraepithelial carcinomas associated with high-grade serous ovarian carcinomas: a systematic review.

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Chen, F; Gaitskell, K; Garcia, M J; Albukhari, A; Tsaltas, J; Ahmed, A A

2017-05-01

Serous tubal intraepithelial carcinomas (STICs) have been documented in high-grade serous ovarian carcinomas (HGSOCs). However, the rate of association between STICs and HGSOCs and, therefore, the fraction of HGSOCs that are likely to have originated from the fallopian tube (FT), has remained unclear. To appraise the literature describing the association between STICs and established HGSOCs. Ovid MEDLINE and EMBASE were searched. Studies were included if they evaluated the frequency of STICs in HGSOCs, and were published in an English peer-reviewed journal. Appropriate studies were evaluated for their compliance with the 'Strengthening and Reporting of Observational Studies in Epidemiology (STROBE)' criteria. Ten articles met the study selection criteria. The reported coexistence between STICs and HGSOCs ranged from 11% to 61% (mean: 31%, 95% CI: 17-46%). STICs were rarely found in other gynaecological cancers. Small sample size, lack of objective criteria to identify STICs and the retrospective nature of the studies contributed to the variability in reporting the rate of the association. STICs were identified commonly in the FTs of women with HGSOC. Finding the true rate of association between STICs and HGSOCs will require further investigations. While there is evidence that a fraction of HGSOCs arise from the FTs, an accurate estimate of that fraction remains to be determined. The lack of an accurate estimate of the association makes it difficult to evaluate the potential magnitude of reduction of HGSOCs following prophylactic salpingectomy. A systematic review of the incidence of STICs in HGSOCs identifies significant methodological inconsistencies. © 2017 Royal College of Obstetricians and Gynaecologists.

Serous tubal intraepithelial neoplasia : The concept and its application

NARCIS (Netherlands)

Meserve, Emily E. K.; Brouwer, Jan; Crum, Christopher P.

In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that

The prognostic significance of virus-associated changes in grade 1 cervical intra-epithelial neoplasia

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Bagi, P; Worning, A M; Nordsten, M

1987-01-01

Virus-associated changes of the cervix uteri were assessed in patients treated for grade 1 cervical intra-epithelial neoplasia (CIN). Of 106 patients evaluated, 67 (63%) had virus-associated changes. The patients were treated without regard to the presence/absence of virus-associated changes. In 26...... patients the treatment was unsuccessful (persistence, recurrence, or progression of the neoplasia). The frequency of treatment failure was 33% in patients with, and 10% in patients without virus-associated changes (p less than 0.025). It is recommended that patients with CIN 1 and virus-associated changes...

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

DEFF Research Database (Denmark)

Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

2010-01-01

To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

Human Papilloma Virus 16 and 18 Association in Cervical Intraepithelial Lesions and Cervical Cancers by In Situ Hybridization

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Mohanty Manisa

2017-03-01

Full Text Available Objective: To correlate the association of high risk Human Papilloma Virus (HPV 16, 18 in cervical intraepithelial lesions and cervical cancers by in-situ hybridization (ISH technique. Study Group: Cervical biopsy and hysterectomy specimen of 78 young and adult women, attending Hi-Tech Medical College and Hospital, Bhubaneswar, who were clinically or cytologically suspected of cervical intraepithelial lesion or cervical cancer were taken as source of target viral DNA. Material: Formalin 10% as fixative H & E stain as routine staining agent In-situ hybridization kit for HPV 16 and 18 DNA. Method: After following standard protocol for surgical grossing, HPV 16, 18 In-situ hybridization kit was used on paraffin embedded tissue sections. Results: The percentage of positive cases was highest in cervical cancer patients followed by cervical intraepithelial lesions, high grade, and low grade. Conclusion: This study has been carried out for the first in our state and our results show high degree of positivity of HPV 16/18 in females with cervical intraepithelial lesions and cervical cancers attending our tertiary care hospital.

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction.

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Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, U; Mosca, Lavinia; Sabatucci, Ilaria; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-01

To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ ( P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

Long-term follow-up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV-negative women after conization

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Gosvig, Camilla F; Huusom, Lene D; Andersen, Klaus K

2015-01-01

Little research has been conducted on the long-term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long-term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we...

EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

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Kodali Venkataramana

2017-03-01

Full Text Available BACKGROUND Cervical cancer is by far the most common human papilloma virus related disease. Nearly, all cases of cervical cancer can be attributable to human papilloma virus infection. Infection with the human papilloma virus is the main risk factors for cervical intraepithelial neoplasia and cervical cancer especially the high-risk types. The aim of the study is to study the prevalence of high-risk human papilloma virus 16 and 18 in various grades of cervical intraepithelial neoplasia. MATERIALS AND METHODS It is a prospective study for a period of two years. 50 cases of cervical intraepithelial neoplasia of various grades on histopathology were included in the study. Polymerase chain reaction DNA sequencing was done in all the cases. The patients were followed up for 1 year with Pap smears and results tabulated. RESULTS 77.77% of cases were human papilloma virus 16 positive and 22.22% for human papilloma virus 18. High-risk human papilloma virus was positive in 66.66% of cases beyond 30 years of age. In cases with positive HPV 16 or 18, 62.5% of CIN 1 cases progressed to CIN 2 on follow up for one year,all the CIN2 cases progressed to CIN 3 and CIN 3 cases persisted in the same phase. CONCLUSION High-risk human papilloma virus testing beyond 30 years should be included in the screening test along with Pap smears.

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.

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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.

Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial.

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Firnhaber, Cynthia; Swarts, Avril; Goeieman, Bridgette; Rakhombe, Ntombi; Mulongo, Masangu; Williamson, Anna-Lise; Michelow, Pam; Ramotshela, Sibongile; Faesen, Mark; Levin, Simon; Wilkin, Timothy

2017-12-15

HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. HIV treatment clinic in Johannesburg, South Africa. We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia

International Nuclear Information System (INIS)

Ogino, Ichiro; Kitamura, Tatsuo; Okajima, Hiroyuki; Matsubara, Sho

1998-01-01

Purpose: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). Methods and Materials: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. Results: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. Conclusions: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy

Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia.

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Morote, Juan; Rigau, Marina; Garcia, Marta; Mir, Carmen; Ballesteros, Carlos; Planas, Jacques; Raventós, Carles X; Placer, José; de Torres, Inés M; Reventós, Jaume; Doll, Andreas

2010-12-01

An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN. The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP). The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN. The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.

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

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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.

Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

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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.

Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China

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Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu

2016-01-01

Abstract The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China. Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results. A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with a rate of 4.2%. The highest positive rate occurred in the ≤24 year-old group for all types of cervical lesions. The prevalence of HPV genotypes in the targeted population with high-grade cervical lesions differs from that of other countries. This

Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma.

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Howitt, Brooke E; Hanamornroongruang, Suchanan; Lin, Douglas I; Conner, James E; Schulte, Stephanie; Horowitz, Neil; Crum, Christopher P; Meserve, Emily E

2015-03-01

Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.

Dysregulation of Autophagy Contributes to Anal Carcinogenesis.

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Evie H Carchman

Full Text Available Autophagy is an intracellular catabolic process that removes and recycles unnecessary/dysfunctional cellular components, contributing to cellular health and survival. Autophagy is a highly regulated cellular process that responds to several intracellular signals, many of which are deregulated by human papillomavirus (HPV infection through the expression of HPV-encoded oncoproteins. This adaptive inhibitory response helps prevent viral clearance. A strong correlation remains between HPV infection and the development of squamous cell carcinoma (SCC of the anus, particularly in HIV positive and other immunosuppressed patients. We hypothesize that autophagy is inhibited by HPV-encoded oncoproteins thereby promoting anal carcinogenesis (Fig 1.HPV16 transgenic mice (K14E6/E7 and non-transgenic mice (FVB/N, both of which do not spontaneously develop anal tumors, were treated topically with the chemical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA, to induce anal cancer. The anuses at different time points of treatment (5, 10, 15 and 20 weeks were analyzed using immunofluorescence (IF for two key autophagy marker proteins (LC3β and p62 in addition to histological grading. The anuses from the K14E6/E7 mice were also analyzed for visual evidence of autophagic activity by electron microscopy (EM. To see if there was a correlation to humans, archival anal specimens were assessed histologically for grade of dysplasia and then analyzed for LC3β and p62 protein content. To more directly examine the effect of autophagic inhibition on anal carcinogenesis, nontransgenic mice that do not develop anal cancer with DMBA treatment were treated with a known pharmacologic inhibitor of autophagy, chloroquine, and examined for tumor development and analyzed by IF for autophagic proteins.Histologically, we observed the progression of normal anoderm to invasive SCC with DMBA treatment in K14E6/E7 mice but not in nontransgenic, syngeneic FVB/N background control mice

Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions

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Bottari, F; Sideri, M; Gulmini, C

2015-01-01

and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia......, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology...

Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.

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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.

EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

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Kodali Venkataramana; Prasad Usha

2017-01-01

BACKGROUND Cervical cancer is by far the most common human papilloma virus related disease. Nearly, all cases of cervical cancer can be attributable to human papilloma virus infection. Infection with the human papilloma virus is the main risk factors for cervical intraepithelial neoplasia and cervical cancer especially the high-risk types. The aim of the study is to study the prevalence of high-risk human papilloma virus 16 and 18 in various grades of cervical intraepithelia...

Patterns of Vaginal, Oral, and Anal Sexual Intercourse in an Urban Seventh-Grade Population

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Markham, Christine M.; Peskin, Melissa Fleschler; Addy, Robert C.; Baumler, Elizabeth R.; Tortolero, Susan R.

2009-01-01

Background: This study examines the prevalence of vaginal, oral, and anal intercourse among a population of urban, public middle school students, the characteristics of early sexual initiators, and the sequence of sexual initiation. Such data are limited for early adolescents. Methods: A total of 1279 seventh-grade students (57.3% female, 43.6%…

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR AND HUMAN PAPILLOMAVIRUS (HPV L1 CAPSID PROTEIN IN CERVICAL SQUAMOUS INTRAEPITHELIAL LESIONS

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Balan Raluca

2010-09-01

Full Text Available We analyzed the immunohistochemical pattern of epidermal growth factor receptor (EGFR in cervical squamous intraepithelial lesions (SILs in correlation with L1 HPV capsid protein, in order to determine the relationship between EGFR expression and the infection status of human papillomavirus (HPV. The study included 40 cases, 24 LSIL (low grade SIL (CIN1, cervical intraepithelial neoplasia and 16 HSIL (high grade SIL (6 cases of CIN2 and 10 cases of CIN3. The immunoexpression of L1 HPV protein was assessed on conventional cervico-vaginal smears and EGFR was immunohistochemically evaluated on the corresponding cervical biopsies. The HPV L1 capsid protein was expressed in 45.83% of LSIL and 25% of HSIL. EGFR was overexpressed in 62,4% of HSIL (58,4% CIN2 and 41,6% CIN3 and 37,6% LSIL. The immunoexpression of L1 HPV has clinical application in the progression assessment of the cervical precancerous lesions without a correlation to the grade of the cervical SIL. EGFR is expressed by all proliferating squamous epithelial cells, thus corresponding with the grade of SIL. The evaluation of EGFR status, correlated with L1 HPV protein expression, can provide useful data of progression risk of cervical squamous intraepithelial lesions

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

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Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

2012-01-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

Increased incidence of cervical intraepithelial neoplasia in young women in the Mitte district, Berlin, Germany.

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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.

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

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Masakazu Sato

Full Text Available 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.

Conization, frozen section examination, and planned hysterectomy in the treatment of high-grade cervical intraepithelial neoplasia Conização, exame de congelação e histerectomia planejada no tratamento de neoplasia intra-epitelial de alto grau

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Jesus Paula Carvalho

2001-12-01

Full Text Available PURPOSE: We tested the role of frozen section examination of the cone specimen in the evaluation of the resection margin status and to rule out invasion in patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five patients with cervical intraepithelial neoplasia underwent conization followed by frozen section examination and planned hysterectomy. The results of the definitive paraffin exam were compared with frozen section examination. RESULTS: In the evaluation of the margins by frozen section examination, 16 patients (64% had positive cone margins and 9 (36% had negative margins. The definitive paraffin examination of margin status was concordant in all the cases. Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was microinvasive. Among the remaining 20 cases, we detected 2 additional microinvasive carcinomas after paraffin study, so the diagnosis of the frozen section examination was concordant with the paraffin sections in 23/25 cases (92%. Two cases of microinvasive carcinoma were diagnosed as cervical intraepithelial neoplasia by frozen section examination and had less than 2 mm stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia, frozen section examination can provide immediate and precise evaluation of the cone margin status in high-grade cervical intraepithelial neoplasia. It can identify frank invasion and permit adequate treatment in a one-stage procedure. In early microinvasive disease, frozen section examination fails to detect the area of invasion but reliably detects clear resection margins.OBJETIVOS: Foi avaliado o papel do exame intra-operatório de congelação no diagnóstico de invasão e no estado das margens cirúrgicas em pacientes com neoplasia intra-epitelial de alto grau. CASUÍSTICA E MÉTODO: Vinte e cinco pacientes com neoplasia intra-epitelial de alto grau foram submetidas a conização cervical seguida de histerectomia. O resultado do exame

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

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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

Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia

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Chen Shaomin

2012-04-01

Full Text Available Abstract Background The amplification of oncogenes initiated by high-risk human papillomavirus (HPV infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions. Methods Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH using chromosome probes to TERC (3q26 and C-MYC (8q24. All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis. Results In the normal, cervical intraepithelial neoplasia grade 1 (CIN1, grade 2 (CIN2, grade 3 (CIN3 and squamous cervical cancer (SCC cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC cases than in the normal and CIN1 cases (p p p > 0.05. Conclusions The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.

Treating High-grade Lesions to Prevent Anal Cancer in HIV-infected People

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This study, called the ANCHOR trial, will investigate whether screening and prevention methods similar to those used to prevent cervical cancer can help prevent anal cancer in HIV-infected men and women.

IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

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Zhang JJ

2017-08-01

Full Text Available Jingjing Zhang,1,* Qing Ji,2,* Chunhua Jiao,3,* Lihua Ren,4 Ye Zhao,4 Yanfang Chen,4 Ruihua Shi,4 Yadong Feng4 1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 2Department of Emergency, Jingjiang People’s Hospital, Jingjiang, 3Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, 4Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The clinical significance of insulin-like growth factor-II mRNA-binding protein-3 (IGF2BP3 in esophageal high-grade intraepithelial neoplasia (HGIN is not clear. This study was designed to characterize the expression of IGF2BP3 in HGIN. Patients and methods: IGF2BP3 expression was evaluated by Western blot analyses in 12 cases and by immunohistochemistry (IHC in 112 cases. The associations between IGF2BP3 expression in HGIN and the clinicopathological parameters were examined. Results: Moderate to strong IGF2BP3 expression was present in HGIN samples. Using IHC, it was found that IGF2BP3 was positive in 68 (60.71% cases. Intense IHC of IGF2BP3 in HGIN was associated with a deeper lesion depth, and the lesion depth was the only predictor of the positive expression of IGF2BP3. Conclusion: Our results suggested that IGF2BP3 may be a supplementary tissue marker for preoperative diagnosis of HGIN. Keywords: esophageal squamous cell carcinoma, precancerous lesion, immunohistochemistry detection, early diagnosis

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

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Lucio Dell'Atti

Full Text Available ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa after a high-grade prostatic intraepithelial neoplasia (HGPIN diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4% patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001, Gleason score distribution (p<0.001, and number of positive biopsy cores (p<0.002 between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001. Moreover, increasing duration of metformin assumption (≥2 years was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Molecular events leading to HPV-induced high grade neoplasia

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Saskia M. Wilting

2016-12-01

Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years.

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Silver, Michelle I; Gage, Julia C; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Katki, Hormuzd A; Locke, Alexander; Kinney, Walter K; Castle, Philip E

2018-03-01

Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2 + Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2 + might not be necessary after a negative cotest. Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more

High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

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Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

2014-01-01

OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection

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Jensen, Kirsten E; Thomsen, Louise T; Schmiedel, Sven

2014-01-01

Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithel...... intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection.......Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical...

HPV and anal cancer in HIV-infected individuals: a review

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Schim van der Loeff, Maarten F.; Mooij, Sofie H.; Richel, Oliver; de Vries, Henry J. C.; Prins, Jan M.

2014-01-01

HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade

The negative predictive value of p16INK4a to assess the outcome of cervical intraepithelial neoplasia 1 in the uterine cervix

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Hariri, Jalil; Øster, Anne

2007-01-01

The immunohistochemical expression of p16 in formalin-fixed and paraffin-embedded histological sections was evaluated in a retrospective study comprising a low-grade group of 100 cases of cervical intraepithelial neoplasia (CIN) 1, a high-grade group of 50 cases of CIN 2 to 3, and a benign group...

Frequency of "incidental" serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study.

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Meserve, Emily E K; Mirkovic, Jelena; Conner, James R; Yang, Eric; Muto, Michael G; Horowitz, Neil; Strickland, Kyle C; Howitt, Brooke E; Crum, Christopher P

2017-07-01

Objective The purpose of this study was to determine the prevalence of incidentally discovered serous tubal intraepithelial carcinoma in women without a genetic risk for or history of high grade serous carcinoma (HGSC) in the gynecologic tract. All pathology reports at our institution that included bilateral salpingectomies from January 2006-December 2011 were examined in women >50years old in which the entire tube or the distal one-third was examined histologically with the complete (proximal and distal fallopian tube) or modified (distal one third of the tube) SEE-FIM protocol. Cases were divided into: Group 1, a history of or known risk factors (BRCA1 or BRCA2 mutations) for HGSC and Group 2, those without these attributes for whom a STIC would be unexpected (incidental). Women undergoing unspecified "risk-reducing" procedures were included in Group 1. Of 4051 identified total, 2268 had complete examination of the distal fallopian tube and were age 50 or above. Of these, 1747 were in group 2. Two STICs were identified (0.1%), one associated with a grade 2 endometrial endometrioid adenocarcinoma and one with a low-grade ovarian serous carcinoma in the setting of a serous borderline tumor. Incidental STICs in women over age 50 are uncommon. However, the significance of lesser tubal atypias (0.3% in this study), risk of STIC in women with no epithelial pathology and the risk imposed by coexisting endometrioid neoplasia are unclear and require further study. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between aerobic vaginitis, bacterial vaginosis and squamous intraepithelial lesion of low grade.

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Jahic, Mahira; Mulavdic, Mirsada; Hadzimehmedovic, Azra; Jahic, Elmir

2013-01-01

To determine frequency of HPV infection, aerobic vaginitis and bacterial vaginosis in respondents with squamous intraepithelial lesion of lower grade comparing to respondents with normal PAP test results. Prospective research of 100 respondents has been conducted at University-Clinic Center Tuzla and Gynecology and Obstetrics Department at Primary Health Care Center Tuzla in period from May 2011 untill January 2012. Examination program included: anamnesis, clinical gynecological examination, HPV typization, microbiological examination of vaginal and cervical smear and PAP test. High risk HPV group has been found more frequently among the respondents with LG SIL 46% (23) than in those with normal PAP result 14% (7) p vaginitis has been found in the respondents with LG SIL in 28% (14) and there is statistically significant difference of this vaginitis comparing to the respondents with normal PAP result (p vaginitis in 9 cases E. coli has been isolated, in 4 E. faecalis and in 1 Staphylococcus aureus, while in women with normal PAP test results 3 cases of E.coli have been isolated. Examining changes in pH value of vaginal environment, higher measured values have been found in the respondents with LG SIL- 5.26 while in the respondents with normal PAP test result was 4.94 (p vaginitis is very common but is not an indicator of HPV infection. An adequate treatment of aerobic vaginitis would decrease the frequency of LG SIL and number of precancerous lesions which may

Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia

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Cléber Sergio da Silva

2010-01-01

Full Text Available OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas. The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3, 35.5 (± 9.5, and 50 (± 11.2 years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3, cytotoxic lymphocytes (CD8, B lymphocytes (CD20, macrophages (CD68 and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control, at the intraepithelial lesion (CIN cases, and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05 in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05. CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

Clinical performance of a human papillomavirus messenger RNA test (Aptima HPV Assay) on residual material from archived 3-year-old PreservCyt samples with low-grade squamous intraepithelial lesion

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Waldstrøm, Marianne; Ornskov, Dorthe

2011-01-01

Human papillomavirus (HPV) testing is widely used in the triage of women with a borderline smear result but the efficiency of testing women with low-grade squamous intraepithelial lesion (LSIL) is less clear, mainly because of lack of specificity. New HPV tests are emerging, which detect E6/E7...

Neoplasia intraepitelial cervical de alto grau durante a gestação: experiência de um serviço do Sul do Brasil High-grade cervical intraepithelial neoplasia during pregnancy: experience in a service in southern Brazil

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Vinícius Basso Preti

2009-12-01

Full Text Available OBJETIVO: avaliar o tratamento instituído a portadoras de neoplasia intraepitelial cervical de alto grau e o seguimento destas pacientes durante a gestação. MÉTODOS: estudo retrospectivo baseado na revisão dos prontuários de 30 pacientes atendidas no período de 1990 a 2002 no Hospital Erasto Gaertner, com diagnóstico de neoplasia intraepitelial cervical de alto grau durante a gestação. O diagnóstico foi realizado por colposcopia e biópsia, e a colposcopia foi realizada novamente durante o período gestacional e após o parto. Foram avaliados os diagnósticos de regressão e progressão das lesões. RESULTADOS: das 30 pacientes, 3 foram excluídas por não-confirmação do diagnóstico de lesão intraepitelial escamosa de alto grau (LEAG pela colposcopia com biópsia. Quatro pacientes foram submetidas ao tratamento durante a gestação, e uma delas apresentou parto pré-termo na 32ª semana de gestação. Vinte e três pacientes foram submetidas a tratamento expectante, realizando-se nova colposcopia e biópsia, sendo então submetidas à conização ou cirurgia de alta frequência em média na 11ª semana de gestação. Em 7,4% dos casos houve regressão da lesão na peça cirúrgica, embora a biópsia evidenciasse lesão de alto grau após o término da gestação. CONCLUSÕES: toda paciente com diagnóstico de lesão intraepitelial escamosa de alto grau (LEAG deve ser submetida à colposcopia e biópsia para excluir lesão invasiva. A conduta expectante para as lesões intraepiteliais é o tratamento de escolha e mais seguro pela possibilidade de regressão destas lesões no período pós-parto.PURPOSE: to evaluate the results of treatment to which patients with high grade intraepithelial cervical neoplasia (HSIL are submitted, as well as their follow-up during pregnancy. METHODS: retrospective study based on the review of the medical report of 30 patients with diagnosis of high-grade squamous intraepithelial lesions (HSIL during

LEF1 is preferentially expressed in the tubal-peritoneal junctions and is a reliable marker of tubal intraepithelial lesions.

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Schmoeckel, Elisa; Odai-Afotey, Ashley A; Schleißheimer, Michael; Rottmann, Miriam; Flesken-Nikitin, Andrea; Ellenson, Lora H; Kirchner, Thomas; Mayr, Doris; Nikitin, Alexander Yu

2017-09-01

Recently it has been reported that serous tubal intraepithelial carcinoma (STIC), the likely precursor of ovarian/extra-uterine high-grade serous carcinoma, are frequently located in the vicinity of tubal-peritoneal junctions, consistent with the cancer-prone features of many epithelial transitional regions. To test if p53 (aka TP53)-signatures and secretory cell outgrowths (SCOUTs) also localize to tubal-peritoneal junctions, we examined these lesions in the fallopian tubes of patients undergoing salpingo-oophorectomy for sporadic high-grade serous carcinomas or as a prophylactic procedure for carriers of familial BRCA1 or 2 mutations. STICs were located closest to the tubal-peritoneal junctions with an average distance of 1.31 mm, while SCOUTs were not detected in the fimbriated end of the fallopian tube. As many epithelial transitional regions contain stem cells, we also determined the expression of stem cell markers in the normal fallopian tube, tubal intraepithelial lesions and high-grade serous carcinomas. Of those, LEF1 was consistently expressed in the tubal-peritoneal junctions and all lesions, independent of p53 status. All SCOUTs demonstrated strong nuclear expression of β-catenin consistent with the LEF1 participation in the canonical WNT pathway. However, β-catenin was preferentially located in the cytoplasm of cells comprising STICs and p53 signatures, suggesting WNT-independent function of LEF1 in those lesions. Both frequency of LEF1 expression and β-catenin nuclear expression correlated with the worst 5-year patient survival, supporting important role of both proteins in high-grade serous carcinoma. Taken together, our findings suggest the existence of stem cell niche within the tubal-peritoneal junctions. Furthermore, they support the notion that the pathogenesis of SCOUTs is distinct from that of STICs and p53 signatures. The location and discrete patterns of LEF1 and β-catenin expression may serve as highly sensitive and reliable ancillary

Human papillomavirus infection among Bangladeshi women with cervical intraepithelial neoplasia and chronic cervicitis

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Elisha Khandker

2016-01-01

Full Text Available Background and objectives: Cervical cancer is one of the leading causes of morbidity and mortality. Human papillomavirus (HPV is known to be associated with cervical intraepithelial neoplasia (CIN and cancer. The objective of the present study was to determine the rate of HPV infection among the Bangladeshi women with different grades of CIN and cancer. Methods: Women aged 20 to 55 years, diagnosed as a case of chronic cervicits, cervical intraepithelial neoplasia (CIN or invasive cancer by Papanicolaou (Pap smear and colposcopy directed biopsy were enrolled in the study. High and intermediate risk oncogenic HPV were detected in cervical samples by real time PCR (rt-PCR. Results: Seventy two women with chronic cervicitis and different grades of CIN were included in the study. Out of 72 cases, 28 (38.9% and 44 (61.1% had chronic cervicitis and CIN respectively. Overall, the HPV infection rate was 43.1% (95% CI= 32%-54% among the study population. CIN cases had significantly high (p<0.01 HPV infection (78.6%; 95% CI=60%-89% compared to cases with chronic cervicitis (18.2%; 95% CI=11.1%-34.5%. Women between the age of 20-30 years had the highest positive rate (50.0% followed by 31-40 years age group (43.6%. All CIN grade 2 and 3 had HPV infection. Conclusion: The study showed that HPV was strongly associated with different grades of CIN. Specific HPV types should be determined to find out the most prevalent HPV types among the Bangladeshi women with CIN and cervical cancers. IMC J Med Sci 2016; 10(1: 29-32

High-grade cervical lesions among women attending a reference clinic in Brazil: associated factors and comparison among screening methods.

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Neide T Boldrini

Full Text Available Although screening for cervical cancer is recommended for women in most countries, the incidence of cervical cancer is greater in developing countries. Our goal was to determine the prevalence and factors associated with high-grade lesions/cervical cancer among women attending a reference clinic in Brazil and evaluate the correlation of histology with cytology, colposcopy and the high-risk HPV (HR-HPV tests.A cross-sectional study of women attending a colposcopy clinic was carried out. The patients were interviewed to collect demographic, epidemiological and clinical data. Specimens were collected for cervical cytology, Chlamydia trachomatis and HPV testing using the Hybrid Capture (HC and PCR tests. Colposcopy was performed for all patients and biopsy for histology when cell abnormalities or cervical intraepithelial neoplasia (CIN were present.A total of 291 women participated in the study. The median age was 38 years (DIQ: 30-48 years. The prevalence of histologically confirmed high-grade lesions/cervical cancer was 18.2% (95%, CI: 13.8%-22.6%, with 48 (16.5% cases of CIN-2/CIN-3 and 5 (1.7% cases of invasive carcinoma. In the final logistic regression model, for ages between 30 and 49 years old [OR = 4.4 (95%: 1.01-19.04, history of smoking [OR = 2.4 (95%, CI: 1.14-5.18], practice of anal intercourse [OR = 2.4 (95%, CI: 1.10-5.03] and having positive HC test for HR-HPV [OR = 11.23 (95%, CI: 4 0.79-26, 36] remained independently associated with high-grade lesions/cervical cancer. A total of 64.7% of the cases CIN-3\\Ca in situ were related to HPV-16. Non-oncogenic HPV were only found in CIN-1 biopsy results. Compared to histology, the sensitivity of cytology was 31.8%, the specificity 95.5%; the sensitivity of colposcopy for high-grade lesions/cervical cancer was 51.0%, specificity was 91.4% and the concordance with HPV testing was high.The results confirm an association of HR-HPV with precursor lesions for cervical cancer

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

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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.

HAART slows progression to anal cancer in HIV-infected MSM.

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Duncan, Katrina C; Chan, Keith J; Chiu, Connie G; Montaner, Julio S G; Coldman, Andy J; Cescon, Angela; Au-Yeung, Christopher G; Wiseman, Sam M; Hogg, Robert S; Press, Natasha M

2015-01-28

Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/μl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/μl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/μl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions.

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Chumworathayi, Bandit; Thinkhamrop, Jadsada; Blumenthal, Paul D; Thinkhamrop, Bandit; Pientong, Chamsai; Ekalaksananan, Tipaya

2010-02-01

To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation). HPV DNA typing by polymerase chain reaction and reverse line blot hybridization were used to identify 14 high-risk types and 23 low-risk types. HPV DNA sequencing was also used for other types. Between December 2007 and March 2009, 100 women were recruited to the study and 60 cases had positive results on HPV testing. Twenty-nine patients were randomly allocated to the cryotherapy group and 31 to the observation group. At 1 year, 89.7% (26/29; 95% CI, 78.6-100%) of the cryotherapy group and 90.3% (28/31; 95% CI, 79.9-100%) of the observation group had negative results on HPV testing (0.6% difference; 95% CI, -15.8 to 14.6%, P=0.94). Cryotherapy failed to increase the clearance of prevalent HPV infections among women with LSIL, although in both arms the clearance rates were above 80%. However, in coupling with visual inspection with acetic acid as a single visit approach, its effect on prevention of HSIL and cervical cancer is still promising. Therefore, cryotherapy should not be withdrawn from such programs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Cancer of the anal canal: Diagnosis, staging and follow-up with MRI

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Durot, Carole; Hoeffel, Christine [Dept. of Radiology, Centre Hospitalo-Universitaire de Reims, Reims (France); Dohan, Anthony; Boudiaf, Mourad; Soyer, Philippe [Dept. of Abdominal Imaging, Hopital Lariboisiere-APHP, Paris(France); Servois, Vincent [Dept. of Radiology and Nuclear Medicine, Institut Curie, Paris (France)

2017-11-15

Although a rare disease, anal cancer is increasingly being diagnosed in patients with risk factors, mainly anal infection with the human papilloma virus. Magnetic resonance imaging (MRI) with external phased-array coils is recommended as the imaging modality of choice to grade anal cancers and to evaluate the response assessment after chemoradiotherapy, with a high contrast and good anatomic resolution of the anal canal. MRI provides a performance evaluation of size, extent and signal characteristics of the anal tumor before and after treatment, as well as lymph node involvement and extension to the adjacent organs. MRI is also particularly helpful in the assessment of complications after treatment, and in the diagnosis for relapse of the diseases.

Cancer of the anal canal: Diagnosis, staging and follow-up with MRI

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Durot, Carole; Hoeffel, Christine; Dohan, Anthony; Boudiaf, Mourad; Soyer, Philippe; Servois, Vincent

2017-01-01

Although a rare disease, anal cancer is increasingly being diagnosed in patients with risk factors, mainly anal infection with the human papilloma virus. Magnetic resonance imaging (MRI) with external phased-array coils is recommended as the imaging modality of choice to grade anal cancers and to evaluate the response assessment after chemoradiotherapy, with a high contrast and good anatomic resolution of the anal canal. MRI provides a performance evaluation of size, extent and signal characteristics of the anal tumor before and after treatment, as well as lymph node involvement and extension to the adjacent organs. MRI is also particularly helpful in the assessment of complications after treatment, and in the diagnosis for relapse of the diseases

A Review and Update on Papillary Immature Metaplasia of the Uterine Cervix: A Distinct Subset of Low-Grade Squamous Intraepithelial Lesion, Proposing a Possible Cell of Origin.

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Hong, Soon Auck; Yoo, Su Hyun; Choi, Jene; Robboy, Stanley J; Kim, Kyu-Rae

2018-04-13

- Papillary immature metaplasia (PIM) is a known papillary cervical lesion associated with low-risk human papilloma virus (LR-HPV). - To evaluate additional clinicopathologic features and the HPV genotypes of PIM and discuss the presumptive cell of origin. - A total of 26 PIM cases were evaluated by p16 INK4a , cytokeratin (CK) 7, and CK17 immunohistochemical stainings. Human papilloma virus genotyping was performed, by using HPV DNA Chip, HPV polymerase chain reaction (PCR), and real-time PCR. - Histologically, PIM forms either a papillary mass (n = 21 of 26, 81%) or a slightly elevated/flat plaque (n = 5, 19%). All cases contain variable amounts of mucinous epithelia within the lesions. Koilocytosis was identified in 15 of the 26 cases (58%). Sixteen cases (61%) were associated with LR-HPV (types 6, 11, or 42), but 3 cases (12%) with high-risk (HR) HPV (16, 16/18, and 33), 2 cases (8%) with mixed LR- and HR-HPV (6/16 and 11/58), while 2 cases (8%) were negative, but p16 INK4a immunostaining showed nonblock positivity in all cases. Eight (31%) had high-grade squamous intraepithelial lesion (HSIL) in the adjacent mucosa, 4 (50%) of which showed direct continuity. Identical HPV subtypes were confirmed in separately microdissected cases from PIM and adjacent HSIL. Most lesions (n = 24, 92%) expressed CK17 (reserve cell marker) in a bottom-heavy pattern and CK7 (squamocolumnar junction [SCJ] marker) in a top-heavy pattern, while most cases of low-grade squamous intraepithelial lesion (LSIL) were negative for both markers. - Our results suggest that PIM is a distinct subset of LSIL showing a productive HPV infection, but PIM involves the transformation zone and is proximal to SCJ, while LSIL is mostly from ectocervix or distal to the SCJ.

Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia

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Lu Zhouping

2011-07-01

Full Text Available Abstract Background D2-40 has been shown a selective marker for lymphatic endothelium, but also shown in the benign cervical basal cells. However, the application of D2-40 immunoreactivity in the cervical basal cells for identifying the grade of cervical intraepithelial neoplasia (CIN has not been evaluated. Methods In this study, the immunoreactive patterns of D2-40, compared with p16INK4A, which is currently considered as the useful marker for cervical cancers and their precancerous diseases, were examined in total 125 cervical specimens including 32 of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and p16INK4A immunoreactivities were scored semiquantitatively according to the intensity and/or extent of the staining. Results Diffuse D2-40 expression with moderate-to-strong intensity was seen in all the normal cervical epithelia (21/21, 100% and similar pattern of D2-40 immunoreactivity with weak-to-strong intensity was observed in CIN1 (31/32, 97.2%. However, negative and/or focal D2-40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2% and CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%. On the other hand, diffuse immunostaining for p16INK4A was shown in 37.5% of CIN1, 64.9% of CIN2, and 80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated with the p16INK4A immunoreactivity. Conclusions Immunohistochemical analysis of D2-40 combined with p16INK4A may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia, especially for distinguishing CIN1 from CIN2/3.

Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

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Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

2015-01-01

with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18......In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women...

Role of active and passive smoking in high-risk human papillomavirus infection and cervical intraepithelial neoplasia grade 2 or worse.

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Feng, Rui Mei; Hu, Shang Ying; Zhao, Fang Hui; Zhang, Rong; Zhang, Xun; Wallach, Asya Izraelit; Qiao, You Lin

2017-09-01

We performed a pooled analysis to examine cigarette smoking and household passive smoke exposure in relation to the risk of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia grade 2+ (CIN2+). Data were pooled from 12 cross-sectional studies for cervical cancer screenings from 10 provinces of China in 1999-2007. A total of 16,422 women were analyzed, along with 2,392 high-risk-HPV (hr-HPV) positive women and 381 CIN2+ cases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. There was an excess risk between active smoking and hr-HPV infection and CIN2+. Adjusted OR for ever smokers vs. never smokers was 1.45 (95% CI=1.10-1.91), for hr-HPV infection and 1.89 (95% CI=1.03-3.44), for CIN2+. Passive smoking had a slightly increased risk on the hr-HPV infection with adjusted OR 1.11 (1.00-1.24), but no statistical association was observed between passive smoke exposure and CIN2+. Compared with the neither active nor passive smokers, both active and passive smokers had a 1.57-fold (95% CI=1.14-2.15) increased risk of HPV infection and a 1.99-fold (95% CI=1.02-3.88) risk of CIN2+. Our large multi-center cross-sectional study found active smoking could increase the risk of overall hr-HPV infection and CIN2+ adjusted by passive smoking and other factors. Passive smoking mildly increased the risk of HPV infection but not the CIN2+. An interaction existed between passive tobacco exposure and active smoking for hr-HPV infection and the CIN2+. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

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Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

2014-01-01

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

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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

Photodynamic therapy of cervical intraepithelial neoplasia

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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.

High survivin expression as a risk factor in patients with anal carcinoma treated with concurrent chemoradiotherapy

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Fraunholz, Ingeborg; Rödel, Claus; Distel, Luitpold; Rave-Fränk, Marget; Kohler, Daniela; Falk, Stefan; Rödel, Franz

2012-01-01

To investigate the prognostic value of survivin expression in pretreatment specimens from patients with anal cancer treated with concurrent 5-FU and mitomycin C-based chemoradiation (CRT). Immunohistochemical staining for survivin was performed in pretreatment biopsies of 62 patients with anal carcinoma. Survivin expression was correlated with clinical and histopathological characteristics as well as local failure free- (LFFS), distant metastases free- (DMFS), cancer specific- (CSS), and overall survival (OS). Survivin staining intensity was weak in 10%, intermediate in 48% and intense in 42% of the patients. No association between survivin expression and clinicopathologic factors (tumor stage, age and HIV status) could be shown. In univariate analysis, the level of survivin staining was significantly correlated with DMFS (low survivin vs. high survivin: 94% vs. 74%, p = 0.04). T-stage, N-stage and the tumor grading were significantly associated with OS and CSS and with DMFS and LFFS, respectively. In multivariate analysis, survivin was confirmed as independent prognostic parameter for DMFS (RR, 0.04; p = 0.02) and for OS (RR, 0.27; p = 0.04). Our results demonstrated that the level of pretreatment survivin is correlated with the clinical outcome in patients with anal carcinoma treated with concurrent CRT. Further studies are warranted to elucidate the complex role of survivin for the oncologic treatment and to exploit the protein as a therapeutic target in combined modality treatment of anal cancer

Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: A 12 months analysis after three consecutive prostate biopsies

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Cosimo De Nunzio

2013-06-01

Full Text Available Purpose: To evaluate the risk of prostate cancer (PCa on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN. Materials and methods: From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE were scheduled for trans-rectal ultrasound (TRUS guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. Results: A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22% men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34% still showed HGPIN, 15 (35% were diagnosed with PCa and 9 (21% presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04. Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. Conclusions: Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.

Prognostic significance of epithelial/stromal caveolin-1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density.

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Mohammed, Dareen A; Helal, Duaa S

2017-03-01

Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (PCa). Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25), HGPIN (20) and PCa (20). Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Prognostic significance of epithelial/stromal caveolin‐1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density

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Dareen A. Mohammed

2017-03-01

Full Text Available Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH, high grade prostatic intraepithelial neoplasia (HGPIN and prostatic carcinoma (PCa. Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25, HGPIN (20 and PCa (20. Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Conclusions: Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis.

Drug addiction is not an independent risk factor for oncogenic human papillomavirus infections or high-grade cervical intraepithelial neoplasia: case-control study nested within the Latin American Screening study cohort.

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Syrjänen, K; Naud, P; Derchain, S; Roteli-Martins, C; Longatto-Filho, A; Tatti, S; Branca, M; Erzen, M; Hammes, L S; Matos, J; Gontijo, R; Sarian, L; Bragança, J; Arlindo, F C; Maeda, M Y S; Lörincz, A; Dores, G B; Costa, S; Syrjänen, S

2008-04-01

Drug abuse (addiction) has been listed among the risk factors for human papillomavirus (HPV) infections, but no case-control studies exist to rule out sexual behaviour and other potential confounders. The aim of this study is to evaluate the role of drug addiction as an independent predictor of HR-HPV infections and (cervical intraepithelial neoplasia) CIN2+ in an age-matched case-control (1:4) study nested within the prospective Latin American Screening (LAMS) study cohort. All 109 women in the LAMS cohort (n=12,114) reporting drug abuse/addiction were matched with four controls (n = 436) of non-abusers strictly by age. Conditional logistic regression analysis was used to estimate the co-variates of drug abuse, and the whole series (n=545) was analysed for predictors of HR-HPV and CIN2+ using univariate and multivariate regression models. Oncogenic HPV infections were significantly (P=0.019) more prevalent among abusers (37.7%) than in controls (21.9%), but there was no difference in high-grade squamous intraepithelial lesions (P=0.180) or CIN2+ lesions (P=0.201). In multivariate conditional logistic regression, number of lifetime sexual partners (P=0.0001), ever smokers (P=0.0001), non-use of OCs (P=0.013), ever having sexually transmitted diseases (STD) (P=0.041) and no previous Pap smear (P=0.027) were independent co-variates of drug addiction. Drug abuse was not an independent risk factor of high-risk (HR)-HPV infection, which was significantly predicted by (1) age below 30 years (P=0.045), (2) more than five lifetime sexual partners (P=0.046) and (3) being current smoker (P=0.0001). In multivariate model, only HR-HPV infection was an independent risk factor of CIN2+ (P=0.031), with adjusted OR=11.33 (95% CI 1.25-102.50). These data indicate that drug addiction is not an independent risk factor of either HR-HPV infections or CIN2+, but the increased prevalence of HR-HPV infections is explained by the high-risk sexual behaviour and smoking habits of these women.

Interstitial high-dose rate brachytherapy as boost for anal canal cancer

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Falk, Alexander Tuan; Claren, Audrey; Benezery, Karen; François, Eric; Gautier, Mathieu; Gerard, Jean-Pierre; Hannoun-Levi, Jean-Michel

2014-01-01

To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time

Long-term adherence to follow-up after treatment of cervical intraepithelial neoplasia

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Barken, Sidsel S; Lynge, Elsebeth; Andersen, Erik S.

2013-01-01

OBJECTIVE: To measure adherence to annual follow-up among women treated for cervical intraepithelial neoplasia. DESIGN: Prospective, population-based, register study. SETTING: Denmark, 1996-2007. POPULATION: All women treated for cervical intraepithelial neoplasia with conization. METHODS: Treated...... was poor in Denmark. Our findings suggest that because of this poor adherence, recommendations for long-term annual follow-up after treatment of cervical intraepithelial neoplasia may not be highly effective. Shorter follow-up schedules using highly sensitive tests appear attractive....

Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia

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Svahn, Malene F; Munk, C; Jensen, S M

2016-01-01

OBJECTIVE: Women with a history of cervical intraepithelial neoplasia grade 3 including adenocarcinoma in situ (CIN3/AIS) may be more prone to develop cancers of the ano-genital region and head-and-neck cancers. The current literature is, however, limited. METHODS: We established a nationwide...

TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma—evidence supporting the clonal relationship of the two lesions

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Kuhn, Elisabetta; Kurman, Robert J; Vang, Russell; Sehdev, Ann Smith; Han, Guangming; Soslow, Robert; Wang, Tian-Li; Shih, Ie-Ming

2016-01-01

Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and ‘primary peritoneal’ (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis. Somatic TP53 mutations were detected in all 29 HGSCs analysed and the identical mutations were detected in 27 of 29 pairs of STICs and concurrent HGSCs. Missense mutations were observed in 61% of STICs and frameshift/splicing junction/nonsense mutations in 39%. Interestingly, there were two HGSCs with two distinctly different TP53 mutations each, but only one of the mutations was detected in the concurrent STICs. Missense mutations were associated with intense and diffuse (≥ 60%) p53 nuclear immunoreactivity, while most of the null mutations were associated with complete loss of p53 staining (p STIC and pelvic HGSC and demonstrate the utility of p53 immunostaining as a surrogate for TP53 mutation in the histological diagnosis of STIC. In this regard, it is important to appreciate the significance of different staining patterns. Specifically, strong diffuse staining correlates with a missense mutation, whereas complete absence of staining correlates with null mutations. PMID:21990067

High grade intraepithelial neoplasia of prostate is associated with values of prostate specific antigen related parameters intermediate between prostate cancer and normal levels

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Nermina Obralic

2011-11-01

Full Text Available High grade prostatic intraepithelial neoplasia (HGPIN is widely regarded as the precancerous. The aim of this study was to determine PSA related parameters in patients with initial PSA values 2-10 ng/mL and diagnosis of HGPIN without finding carcinoma at the time of their first needle biopsy. Study groups consisted of 100 men who were diagnosed HGPIN, 84 with cancer and 183 with benign hyperplasia on first biopsy of prostate. Total PSA and free PSA were measured and ratio free/total PSA and PSA density calculated. Mean values of these parameters were compared, and receiver operating characteristic curves were used for comparison of PSA related parameters to discriminate groups of patients. Total PSA, free PSA level and PSA density in patients with HGPIN (6.388 ng/mL did not differ significantly compared to prostate carcinoma (6.976 ng/mL or benign prostatic hyperplasia (6.07 ng/mL patients. Patients with HGPIN had significantly higher ratio free/total PSA than those with prostate carcinoma (0.168 vs 0.133, but significantly lower than patients with benign prostatic hyperplasia (0.168 vs 0.185. Ratio of free/total PSA significantly discriminate HGPIN from prostate carcinoma with sensitivity 84.52 and specify 45.00 at cut-off point of ≤ 0.18. Values of PSA, free PSA and ratio free/total PSA in cases of HGPIN appear to be intermediate between prostate cancer and normal levels. Ratio of free/total PSA may help in decision to repeat biopsies in the presence of HGPIN on biopsy, without concomitant prostate cancer, in patients suitable for curative treatment, with normal digito-rectal examination and trans-rectal sonography.

High-risk human papilloma virus management in pregnancy with cervical intraepithelial neoplasia during pregnancy and postpartum in China.

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He, Yue; Wu, Yu-Mei; Zhao, Qun; Wang, Tong; Song, Fang; Zhu, Li

2014-02-01

To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk human papilloma virus (HR-HPV) during pregnancy and postpartum in China. In this prospective case-control study, 168 pregnant women with CIN and cervicitis were diagnosed by colposcopic cervical biopsy. All the cases underwent hybrid capture assay version II (HCII) to detect HR-HPV DNA load amounts and the tests were completed in 3-6 months after childbirth. During pregnancy: as the CIN grade increased, the HR-HPV infection rates increased (P = 0.002), but HR-HPV DNA load amounts (in logarithms) did not change obviously (P = 0.719). 3-6 months postpartum: as the CIN grade increased, the natural negative rate of HR-HPV decreased (P = 0.000), while the amount of HR-HPV DNA (in logarithms) increased (P = 0.036); especially the amount of HR-HPV DNA in pregnant women with CINIII was significantly higher than that of other grades. During pregnancy and 3-6 months postpartum : the amount of HR-HPV DNA (in logarithms) during pregnancy was higher than that of 3-6 months postpartum with the same grade of CIN. The findings emphasize the importance of undergoing the HCII test 3-6 months postpartum. It should be noted that HR-HPV may turn negative in pregnancy with CINIII 3-6 months after childbirth. Further treatments of pregnancy with CIN should be considered according to the CIN grade diagnosed by cervical biopsy via colposcopy 3-6 months after birth, but not according to the persistence of HR-HPV during pregnancy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Intraepithelial lymphocytes in relation to NIH category IV prostatitis in autopsy prostate.

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Dikov, Dorian; Bachurska, Svitlana; Staikov, Dimitri; Sarafian, Victoria

2015-07-01

Quantitative analysis of the number, normal and pathologic ratios between lymphocytes and epithelial cells (ECs), and the significance of intraepithelial lymphocytes (IELs) in normal prostatic epithelium, benign prostatic hyperplasia (BPH), and high grade prostatic intraepithelial neoplasia (PIN) in relation to NIH category IV prostatitis (histologic prostatitis: HP) was studied in autopsy prostate. IELs were analysed in 59 autopsy prostates, which was routinely embedded in paraffin and immunohistochemically stained for CD3. An average of 300-500 ECs were counted per case. The number of IELs was calculated as the mean/100 ECs. Category IV prostatitis was evaluated using NIH consensus grading system in terms of anatomical localization and grade. In healthy individuals the mean number of IELs/100 ECs was 0.61 ± 0.34% or ≤1 lymphocyte/100 ECs, which is considered as the normal basal level of prostate IELs. In category IV prostatitis, the mean number of IELs/100 ECs was 8.53 ± 3.25% or 5-11 lymphocytes/100 ECs. The number of IELs in both around and inside inflammation areas correlated to the grade and location of HP (P prostatic inflammation (P prostatic IELs in normal prostate and in relation to category IV prostatitis. The detected normal upper limit of CD3+ IELs is 1 lymphocyte/100 ECs in the normal prostate epithelium. This is considered as an organ specific characteristic of the prostate-associated lymphoid tissue (PALT). Values >5 IELs/100 ECs indicate the presence of category IV prostatitis. The severity of inflammation correlates to the number of IELs. There is an intimate link between the quantity of the IELs, the degree of the severity and the localization of category IV prostatitis. HP is a chronic and dynamic inflammatory process affecting the whole prostate gland. The increased number of IELs suggests the immune or autoimmune character of category IV prostatitis, BPH and inflammatory preneoplastic (PIN) lesions in the prostatic tumor

Effect of green tea catechins in patients with high-grade prostatic intraepithelial neoplasia: Results of a short-term double-blind placebo controlled phase II clinical trial

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Salvatore Micali

2017-10-01

Full Text Available Background and study objective: Several studies suggest a protective role of green tea catechins against prostate cancer (PCa. In order to evaluate the efficacy of green tea catechins for chemoprevention of PCa in patients with high-grade prostate intraepithelial neoplasia (HG-PIN we performed a phase II clinical trial. Methods: Sixty volunteers with HG-PIN were enrolled to carry out a double-blind randomized placebo-controlled phase II clinical trial. Treated group took daily 600 mg of green tea catechins (Categ Plus® for 1 year. Patients were screened at 6 and 12 months through prostatic biopsy and measurements of prostate-specific antigen (PSA. Results: Despite the statistically significant reduction of PSA observed in subjects who received green tea catechins for 6 and 12 months, we did not find any statistical difference in PCa incidence between the experimental groups neither after 6 nor after 12 months. However, throughout the one-year follow- up we observed very limited adverse effects induced by green tea catechins and a not significant improvement in lower urinary tract symptoms and quality of life. Conclusions: Although the small number of patients enrolled in our study and the relatively short duration of intervention, our findings seems to deny the efficacy of green tea catechins. However, results of our clinical study, mainly for its low statistical strength, suggest that the effectiveness of green tea catechins should be evaluated in both a larger cohort of men and longer trial.

Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population

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McIntyre James A

2008-07-01

Full Text Available Abstract Background In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN, the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ. Methods Women with high grade squamous intraepithelial lesions or worse (HSIL, less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression Results The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear. Conclusion We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.

Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study

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Sand, Freja Laerke; Frederiksen, Kirsten; Munk, Christian

2018-01-01

Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918......-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative...... risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according...

Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer.

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Chay, Wen Yee; McCluggage, W Glenn; Lee, Cheng-Han; Köbel, Martin; Irving, Julie; Millar, Joanne; Gilks, C Blake; Tinker, Anna V

2016-03-01

The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data. Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation. Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.

Cervical intraepithelial neoplasia grade 2 or worse in Galicia, Spain: HPV 16 prevalence and vaccination impact.

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Pérez-Castro, Sonia; Lorenzo-Mahía, Yolanda; Iñarrea Fernández, Amparo; Lamas-González, María José; Sarán-Díez, María Teresa; Rubio-Alarcón, Joaquín; Reboredo-Reboredo, María Consuelo; Mosteiro-Lobato, Sonia; López-Miragaya, Isabel; Torres-Piñón, Julio; Melón-García, Santiago

2014-10-01

The etiology of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) can influence the efficacy of Public Health preventive strategies. This study aimed to determine the high-risk papillomavirus (HR-HPV) prevalence in CIN2+ cases in unvaccinated women in Galicia (Spain), the expected impact of bivalent vaccination, and the distribution of HPV 16 in squamous lesions. Ninety-four histologically confirmed cases of CIN2+ (2009-2010) were retrospectively studied: 23 CIN2, 58 CIN3- squamous carcinoma in situ (CIN3-CIS), 5 adenocarcinoma in situ (AIS), and 8 invasive squamous cervical cancer (SCC). Linear Array HPV Genotyping Test (Roche Diagnostics, Mannheim, Germany) was performed on the cervical specimens. Bivalent vaccination impact was calculated, based on regional vaccination coverage data, local HR-HPV prevalence, and reported efficacy (direct and cross-protection) of the vaccine. HR-HPV prevalence was 96.8%. The most frequent genotypes were HPV 16 (48.8-58.2%) and HPV 31 (9.3%-12.1%), considering single infections or single-multiple infections, respectively (hierarchical attribution). In squamous lesions, HPV 16 prevalence in women younger than 45 years of age increased in severe lesions (CIN3-CIS/SCC, OR 4.2), and was higher than in older women (OR 5.5). The vaccine could reduce the cumulative incidence of CIN2+ by 50.6% (direct protection), or by 62.7% (direct and cross-protection). HPV vaccination could have a great impact in women younger than 45 years of age due to the high prevalence of HPV 16 in their lesions. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma--evidence supporting the clonal relationship of the two lesions.

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Kuhn, Elisabetta; Kurman, Robert J; Vang, Russell; Sehdev, Ann Smith; Han, Guangming; Soslow, Robert; Wang, Tian-Li; Shih, Ie-Ming

2012-02-01

Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and 'primary peritoneal' (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis. Somatic TP53 mutations were detected in all 29 HGSCs analysed and the identical mutations were detected in 27 of 29 pairs of STICs and concurrent HGSCs. Missense mutations were observed in 61% of STICs and frameshift/splicing junction/nonsense mutations in 39%. Interestingly, there were two HGSCs with two distinctly different TP53 mutations each, but only one of the mutations was detected in the concurrent STICs. Missense mutations were associated with intense and diffuse (≥ 60%) p53 nuclear immunoreactivity, while most of the null mutations were associated with complete loss of p53 staining (p STIC and pelvic HGSC and demonstrate the utility of p53 immunostaining as a surrogate for TP53 mutation in the histological diagnosis of STIC. In this regard, it is important to appreciate the significance of different staining patterns. Specifically, strong diffuse staining correlates with a missense mutation, whereas complete absence of staining correlates with null mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Audit of paired anal cytology and histopathology outcomes in patients referred to a public sexual health clinic.

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Williams, Vincent M; Metcalf, Cecily; French, Martyn A; McCloskey, Jenny C

2010-09-01

The level of agreement between anal cytology and histopathology is not clear with only a few studies evaluating the reliability of anal specimen reporting. Australian data in relation to this are limited. The results of paired anal cytology and histopathology specimens received between 2002 and 2008 from patients who were referred within the sexual health clinic were retrieved from the anatomical pathology database. A total of 248 paired samples from 154 (21 females, 133 males) participants were extracted. Concurrent high risk human papilloma virus (hrHPV) DNA assay and HIV status for the study group were also collected. Data were tabulated according to reported grade of squamous abnormality based on the Bethesda system. Using the biopsy result as the gold standard the specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for cytology were calculated and the association between grade of abnormality, HIV status and hrHPV infection estimated. Concordance between cytology and histology showed that in 204 (85%) paired samples both tests were categorised as abnormal (Kappa statistic 0.73, P = 0.013). The cytology result showed a sensitivity of 96%, specificity 14%, PPV 89% and NPV 31% when compared with histopathology. HrHPV assay was positive in 192 (80%) samples. High-grade squamous abnormalities were reported in biopsy specimens from 60% (n = 42/67) of HIV-positive subjects and 25% (n = 22/87) of HIV-negative subjects. HIV-positive individuals were more likely to be hrHPV positive, odds ratio (OR) 6.21 [95% confidence interval (CI) 2.69 to 14.34], when compared with HIV-negative subjects. Anal cytology is highly sensitive for the detection of abnormal squamous cells. While cytology has low specificity for predicting the grade of abnormality compared with biopsy outcome, its application as a screening method in asymptomatic at risk populations warrants further study.

[Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus].

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Iribarren-Díaz, Mauricio; Ocampo Hermida, Antonio; González-Carreró Fojón, Joaquín; Alonso-Parada, María; Rodríguez-Girondo, Mar

2014-12-01

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group.

Science.gov (United States)

2000-03-01

Human papillomavirus (HPV) infections appear to be central to the development of cervical cancer. This study addresses the question of whether testing women who have low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix for HPV DNA is useful as a triage strategy. Four clinical centers in different areas of the United States participated in a randomized clinical trial of the use of HPV DNA testing in women with cytologic evidence of atypical squamous cells of undetermined significance (ASCUS) or LSIL. The study sample in this article consists only of women who had LSIL at enrollment. Within 6 months of an LSIL diagnosis (based on a Pap smear read by a community-based cytopathologist), women who were 18 years of age or older completed a standardized questionnaire and underwent a pelvic examination that included collection of cervical specimens for HPV DNA testing by Hybrid Capture II (HCII)(R) assay. Among the 642 women referred with LSIL who had analyzable test results, the mean chronologic age and age at first coitus were similar among the four clinical centers, despite the centers' ethnic and geographic diversity. Overall, HPV DNA was detected in cervical samples from 532 (82.9%) of the 642 women (95% confidence interval = 79.7%-85.7%). This high frequency of HPV positivity was confirmed by polymerase chain reaction (PCR) assays in a subset of 210 paired specimens tested by HCII and PCR (81.4% were positive by both methods). Because a very high percentage of women with an LSIL diagnosis from Pap smears are positive for HPV DNA by HCII testing, there is limited potential for this assay to direct decisions about the clinical management of women with LSIL. The role of HPV testing in the management of women with ASCUS is still under study.

Testing for and the role of anal and rectal sensation.

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Rogers, J

1992-03-01

The rectum is insensitive to stimuli capable of causing pain and other sensations when applied to a somatic cutaneous surface. It is, however, sensitive to distension by an experimental balloon introduced through the anus, though it is not known whether it is the stretching or reflex contraction of the gut wall, or the distortion of the mesentery and adjacent structures which induces the sensation. No specific sensory receptors are seen on careful histological examination of the rectum in humans. However, myelinated and non-myelinated nerve fibres are seen adjacent to the rectal mucosa, but no intraepithelial fibres arise from these. The sensation of rectal distension travels with the parasympathetic system to S2, S3 and S4. The two main methods for quantifying rectal sensation are rectal balloon distension and mucosal electrosensitivity. The balloon is progressively distended until particular sensations are perceived by the patient. The volumes at which these sensations are perceived are recorded. Three sensory thresholds are usually defined: constant sensation of fullness, urge to defecate, and maximum tolerated volume. The modalities of anal sensation can be precisely defined. Touch, pain and temperature sensation exist in normal subjects. There is profuse innervation of the anal canal with a variety of specialized sensory nerve endings: Meissner's corpuscles which record touch sensation, Krause end-bulbs which respond to thermal stimuli, Golgi-Mazzoni bodies and pacinian corpuscles which respond to changes in tension and pressure, and genital corpuscles which respond to friction. In addition, there are large diameter free nerve endings within the epithelium. The nerve pathway for anal canal sensation is via the inferior haemorrhoidal branches of the pudendal nerve to the sacral roots of S2, S3 and S4. Anal sensation may be quantitatively measured in response to electrical stimulation. The technique involves the use of a specialized constant current generator

Oral and anal sex practices among high school youth in Addis Ababa, Ethiopia

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Cherie Amsale

2012-01-01

Full Text Available Abstract Background Understanding the full range of sexual behaviors of young people is crucial in developing appropriate interventions to prevent and control sexually transmitted infections including HIV. However, such information is meager in developing countries. The objective of this study was to describe oral and anal sex practices and identify associated factors among high school youth. Methods A cross-sectional study was conducted among high school youth in Addis Ababa, Ethiopia. A multi-stage sampling procedure was followed to select a representative sample of school youth. The total sample size for this study was 3840. Data were collected using a self-administered questionnaire. Data analysis was guided by the ecological framework. Results The overall proportion of people who reported ever having oral sex was 5.4% (190 and that of anal sex was 4.3% (154. Of these 51.6% (98 had oral sex and 57.1% (87 had anal sex in the past 12 months. Multiple partnerships were reported by 61.2% of the respondents who had oral sex and 51.1% of students practicing anal sex. Consistent condom use was reported by 12.2% of those practicing oral sex and 26.1% of anal sex. Reasons for oral and anal sex included prevention of pregnancy, preserving virginity, and reduction of HIV and STIs transmission. Oral sex practice was strongly and significantly associated with perception of best friends engagement in oral sex (AOR = 5.7; 95% CI 3.6-11.2 and having illiterate mothers (AOR = 11.5; 95%CI 6.4-18.5. Similarly, anal sex practice was strongly and significantly associated with favorable attitude towards anal sex (AOR = 6.2; 95%CI 3.8-12.4, and perceived best friends engagement in anal sex (AOR = 9.7; 95%CI 5.4-17.7. Conclusion Considerable proportion of adolescents had engaged in oral and anal sex practices. Multiple sexual partnerships were common while consistent condom use was low. Sexual health education and behavior change communication strategies need to

Evidence supporting see-and-treat management of cervical intraepithelial neoplasia: a systematic review and meta-analysis.

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Ebisch, R M F; Rovers, M M; Bosgraaf, R P; van der Pluijm-Schouten, H W; Melchers, W J G; van den Akker, P A J; Massuger, L F A G; Bekkers, R L M

2016-01-01

Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014. Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%). The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression. © 2015 Royal College of Obstetricians and Gynaecologists.

Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis.

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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.

Immunostaining of p16INK4a/Ki-67 and L1 Capsid Protein on Liquid-based Cytology Specimens Obtained from ASC-H and LSIL-H Cases

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Byun, Seung Won; Lee, Ahwon; Kim, Suyeon; Choi, Yeong Jin; Lee, Youn Soo; Park, Jong Sup

2013-01-01

Background: Atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and low-grade intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) are ambiguous diagnostic entities for the prediction of high-grade cervical lesion. Objective and reproducible tests for predicting high-grade cervical lesions are needed to reduce unnecessary colposcopic referrals or follow-ups. Objective: We aimed to identify an adequate set of adjunctive ...

High grade serous ovarian carcinomas originate in the fallopian tube.

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Labidi-Galy, S Intidhar; Papp, Eniko; Hallberg, Dorothy; Niknafs, Noushin; Adleff, Vilmos; Noe, Michael; Bhattacharya, Rohit; Novak, Marian; Jones, Siân; Phallen, Jillian; Hruban, Carolyn A; Hirsch, Michelle S; Lin, Douglas I; Schwartz, Lauren; Maire, Cecile L; Tille, Jean-Christophe; Bowden, Michaela; Ayhan, Ayse; Wood, Laura D; Scharpf, Robert B; Kurman, Robert; Wang, Tian-Li; Shih, Ie-Ming; Karchin, Rachel; Drapkin, Ronny; Velculescu, Victor E

2017-10-23

High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease.

Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

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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.

Neoplasia intra-epitelial grau III da vulva e da região perianal tratada com vulvectomia superficial: relato de caso High-grade vulvar and perianal intraepithelial neoplasia treated with skinning vulvectomy: a case report

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Walquíria Quida Salles Pereira Primo

2003-05-01

Full Text Available A neoplasia intra-epitelial vulvar grau III (NIV III se manifesta de modo visível, portanto, acessível à biópsia e, por conseguinte, ao diagnóstico histológico. Há duas formas precursoras do câncer vulvar: a NIV associada ao papiloma vírus humano (HPV e a NIV associada ao líquen simples crônico, hiperplasia de células escamosas e líquen escleroso, não tratados. Porém, pode existir sobreposição das duas formas. O termo papulose bowenóide, apesar de ser desencorajado, define uma das formas clínicas da NIV, que se apresenta como lesões pigmentadas, verruciformes, papulares e múltiplas. A NIV III está associada com HPV em mais de 80% dos casos e em 40% das vezes, nota-se envolvimento perianal. O seu tratamento é muito difícil e pode ocorrer recorrência em qualquer tempo e por muitos anos. Embora não exista tratamento padrão definido, os trabalhos apontam para a cirurgia, respeitando margem de segurança, como o mais adequado.High-grade vulvar intraepithelial neoplasia (VIN III is a visible lesion; therefore, it is accessible to biopsy and thus, to a histological diagnosis. There are two forms of vulvar cancer precursors: VIN caused by human papillomavirus (HPV and VIN associated with untreated lichen simplex chronicus, squamous cell hyperplasia, and lichen sclerosus. There may be overlap of the two forms. The term bowenoid papulosis, although discouraged, identifics a clinical form of VIN III. Such lesion appears as pigmented, wart-like growths or papules. VIN III is associated with HPV in more than 80% of the cases, and there is perianal involvement in 40% of the times. Vulvar intraepithelial neoplasia is difficult to cure and relapses can occur at any time for many years. Although there is no defined standard treatment, studies point to surgery, respecting a free margin, as the most adequate one.

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

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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

Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

DEFF Research Database (Denmark)

Haupt, Richard M; Wheeler, Cosette M; Brown, Darron R

2011-01-01

The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were.......9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond...

Resultados do tratamento do carcinoma espinocelular anal e do seu precursor em doentes HIV-positivos Outcome of treatment of anal squamous cell carcinoma and its precursor in HIV-infected patients

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Sidney Roberto Nadal

2007-08-01

and evolution from HAIN to cancer. This is a report of cases treated at the "Instituto de Infectologia Emílio Ribas", Sao Paulo, Brazil. METHODS: We attended 45 HIV-positive patients between July 1996 and June 2006. Most were male (97.7%, with ages ranging from 23 to 55 years (mean: 38.5 years. Thirty patients had high grade anal intra-epithelial neoplasia (HAIN, treated with local resection, and 15 with anal canal invasive squamous cell carcinoma were first submitted to chemo radiation, while biopsies were obtained during follow-up. RESULTS: Patients with HAIN had recurrences in 16.7% of cases and remained cancer free for up to five years. Chemoradiation was not possible in five patients with invasive carcinoma (40% because three had advanced AIDS and two refused treatment. Eight (88.8% out of nine patients had complete response to chemoradiation and remained cancer free for a period from three to six years. Chemoradiation failed in the ninth patient: abdominal perineal resection was performed, and there was no recurrence over a five-year period. CONCLUSION: We concluded that HAIN can recur after local resection in HIV-positive patients but does not evolve to invasive carcinoma. Invasive cancer can be treated in the same way as in HIV seronegative persons, when clinical conditions permit.

Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

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Soroush Rais-Bahrami

2017-01-01

Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

Prevalence of Specific Types of Human Papiloma Virus in Cervical Intraepithelial Lesions and Cervical Cancer in Macedonian Women

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Aleksioska-Papestiev, Irena; Chibisheva, Vesna; Micevska, Megi; Dimitrov, Goran

2018-01-01

,1% females with CIN 3 and 97,5 % in females with CIS. The lowest prevalence was detected in patients with atypical squamous cells of undetermined significance (ASCUS) (23,9%) and CIN 1-25 (6%). Results of HPV typing show that genotypes were found either single or multiple in both single and multiple infections. We have seen that HPV 16, 18 and 31 were the most common types detected among the patients from Macedonia. HPV 16 was present even in 52,1 % of women with CIS and in 41,2% in women with CIN 3. HPV type 31 ranked second in patients wit CIN1, CIN2, CIN3 but HPV 18 ranked second in patients with CIS with (12,8%). Surprisingly, patients with mixed infection had more low grade intraepithelial squamous lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL) then CIS. Conclusion Among Macedonian women, HPV 16, 31 and 18 were HPV types strongly associated with intraepithelial cervical lesions and cervical cancers. The prevalence of high risk HPV was highest in youngest women, but the risk was highest among patients with invasive cervical cancer (ICC). Surprisingly, patients with mixed infection had more LSIL and HSIL then CIS. PMID:29416214

Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type.

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Maria Persson

Full Text Available Diagnoses of atypical squamous cells of undetermined significance (ASCUS and low-grade squamous intraepithelial lesions (LSIL are common, but the corresponding risk of disease varies by human papillomavirus (HPV status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+ among women with ASCUS/LSIL by age, HPV status, and genotype(s.A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+.In total, 89 women (28.3% developed CIN2+. High-risk (HR HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5-53.5 for HPV16/18; 36.2%, 95% CI: 28.3-45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5-7.8 for HR-HPV-negative women; p<0.0001.HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+.

Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type.

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Persson, Maria; Elfström, K Miriam; Olsson, Sven-Erik; Dillner, Joakim; Andersson, Sonia

2015-01-01

Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s). A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+. In total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5-53.5 for HPV16/18; 36.2%, 95% CI: 28.3-45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5-7.8 for HR-HPV-negative women; p<0.0001). HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+.

Differential gene expression in patients with anal fistula reveals high levels of prolactin recepetor

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Song Yi-Huan

2017-01-01

Full Text Available Background/Aim. There are limited data examining variations in the local expression of inflammatory mediators in anal fistulas where it is anticipated that an improved understanding of the inflammatory milieu might lead to the potential therapeutic option of instillation therapy in complicated cases. The aim of the present study was to examine prolactin receptors (PRLR as inflammatory markers and to correlate their expression with both the complexity of anal fistulas and the likelihood of fistula recurrence. Methods. Microarray was used to screen the differentially expressed gene profile of anal fistula using anal mucosa samples with hemorrhoids with ageand sex-matched patients as controls and then a prospective analysis of 65 patients was conducted with anal fistulas. PRLR immunohistochemistry was performed to define expression in simple, complex and recurrent anal fistula cases. The quantitative image comparison was performed combining staining intensity with cellular distribution in order to create high and low score PRLR immunohistochemical groupings. Results. A differential expression profile of 190 genes was found. PRLR expression was 2.91 times lower in anal fistula compared with control. Sixty-five patients were assessed (35 simple, 30 complex cases. Simple fistulas showed significantly higher PRLR expression than complex cases with recurrent fistulae showing overall lower PRLR expression than de novo cases (p = 0.001. These findings were reflected in measurable integrated optical density for complex and recurrent cases (complex cases, 8.31 ± 4.91 x 104 vs simple cases, 12.30 ± 6.91 x 104; p < 0.01; recurrent cases, 7.21 ± 3.51 x 104 vs primarily healing cases, 8.31 ± 4.91 x 104; p < 0.05. In univariate regression analysis, low PRLR expression correlated with fistula complexity; a significant independent effect maintained in multivariate analysis odds ratio [(OR low to high PRLR expression = 9.52; p = 0.001]. Conclusion. PRLR

The indicating FTA elute cartridge a solid sample carrier to detect high-risk HPV and high-grade cervical lesions.

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de Bie, Roosmarie P; Schmeink, Channa E; Bakkers, Judith M J E; Snijders, Peter J F; Quint, Wim G V; Massuger, Leon F A G; Bekkers, Ruud L M; Melchers, Willem J G

2011-07-01

The clinically validated high-risk human papillomavirus (hrHPV) Hybrid Capture 2 (HC2) and GP5+/6+-PCR assays were analyzed on an Indicating FTA Elute cartridge (FTA cartridge). The FTA cartridge is a solid dry carrier that allows safe transport of cervical samples. FTA cartridge samples were compared with liquid-based samples for hrHPV and high-grade cervical intraepithelial neoplasia (CIN) detection. One cervical sample was collected in a liquid-based medium, and one was applied to the FTA cartridge. DNA was eluted directly from the FTA cartridge by a simple elution step. HC2 and GP5+/6+-PCR assays were performed on both the liquid-based and the FTA-eluted DNA of 88 women. Overall agreement between FTA and liquid-based samples for the presence of hrHPV was 90.9% with GP5+/6+-PCR and 77.3% with HC2. The sensitivity for high-grade CIN of hrHPV testing on the FTA cartridges was 84.6% with GP5+/6+-PCR and only 53.8% with HC2. By comparison, these sensitivities on liquid-based samples were 92.3% and 100% for GP5+/6+-PCR and HC2, respectively. Therefore, the FTA cartridge shows reasonably good overall agreement for hrHPV detection with liquid-based media when using GP5+/6+-PCR but not HC2 testing. Even with GP5+/6+-PCR, the FTA cartridge is not yet capable of detecting all high-grade CIN lesions. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

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Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

2017-10-01

The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society. © 2017 American Cancer Society.

A prediction model for spontaneous regression of cervical intraepithelial neoplasia grade 2, based on simple clinical parameters.

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Koeneman, Margot M; van Lint, Freyja H M; van Kuijk, Sander M J; Smits, Luc J M; Kooreman, Loes F S; Kruitwagen, Roy F P M; Kruse, Arnold J

2017-01-01

This study aims to develop a prediction model for spontaneous regression of cervical intraepithelial neoplasia grade 2 (CIN 2) lesions based on simple clinicopathological parameters. The study was conducted at Maastricht University Medical Center, the Netherlands. The prediction model was developed in a retrospective cohort of 129 women with a histologic diagnosis of CIN 2 who were managed by watchful waiting for 6 to 24months. Five potential predictors for spontaneous regression were selected based on the literature and expert opinion and were analyzed in a multivariable logistic regression model, followed by backward stepwise deletion based on the Wald test. The prediction model was internally validated by the bootstrapping method. Discriminative capacity and accuracy were tested by assessing the area under the receiver operating characteristic curve (AUC) and a calibration plot. Disease regression within 24months was seen in 91 (71%) of 129 patients. A prediction model was developed including the following variables: smoking, Papanicolaou test outcome before the CIN 2 diagnosis, concomitant CIN 1 diagnosis in the same biopsy, and more than 1 biopsy containing CIN 2. Not smoking, Papanicolaou class predictive of disease regression. The AUC was 69.2% (95% confidence interval, 58.5%-79.9%), indicating a moderate discriminative ability of the model. The calibration plot indicated good calibration of the predicted probabilities. This prediction model for spontaneous regression of CIN 2 may aid physicians in the personalized management of these lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioral and psychosocial effects of two middle school sexual health education programs at tenth-grade follow-up.

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Markham, Christine M; Peskin, Melissa F; Shegog, Ross; Baumler, Elizabeth R; Addy, Robert C; Thiel, Melanie; Escobar-Chaves, Soledad Liliana; Robin, Leah; Tortolero, Susan R

2014-02-01

An earlier randomized controlled trial found that two middle school sexual education programs-a risk avoidance (RA) program and a risk reduction (RR) program-delayed initiation of sexual intercourse (oral, vaginal, or anal sex) and reduced other sexual risk behaviors in ninth grade. We examined whether these effects extended into 10th grade. Fifteen middle schools were randomly assigned to RA, RR, or control conditions. Follow-up surveys were conducted with participating students in 10th grade (n = 1,187; 29.2% attrition). Participants were 60% female, 50% Hispanic, and 39% black; seventh grade mean age was 12.6 years. In 10th grade, compared with the control condition, both programs significantly delayed anal sex initiation in the total sample (RA: adjusted odds ratio [AOR], .64, 95% confidence interval [CI], .42-.99; RR: AOR, .65, 95% CI, .50-.84) and among Hispanics (RA: AOR, .53, 95% CI, .31-.91; RR: AOR, .82, 95% CI, .74-.93). Risk avoidance students were less likely to report unprotected vaginal sex, either by using a condom or by abstaining from sex (AOR: .61, 95% CI, .45-.85); RR students were less likely to report recent unprotected anal sex (AOR: .34, 95% CI, .20-.56). Both programs sustained positive impact on some psychosocial outcomes. Although both programs delayed anal sex initiation into 10th grade, effects on the delayed initiation of oral and vaginal sex were not sustained. Additional high school sexual education may help to further delay sexual initiation and reduce other sexual risk behaviors in later high school years. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

Residual disease and HPV persistence after cryotherapy for cervical intraepithelial neoplasia grade 2/3 in HIV-positive women in Kenya.

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Hugo De Vuyst

Full Text Available To assess residual cervical intraepithelial neoplasia (CIN 2/3 disease and clearance of high-risk (hr human papillomavirus (HPV infections at 6 months after cryotherapy among HIV-positive women.Follow-up study.79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy and after cryotherapy (cells.At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI: 66.4-85.9. 18 women (22.8% had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2-15.0 among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9-70. The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively.Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity.

Residual Disease and HPV Persistence after Cryotherapy for Cervical Intraepithelial Neoplasia Grade 2/3 in HIV-Positive Women in Kenya

Science.gov (United States)

De Vuyst, Hugo; Mugo, Nelly R.; Franceschi, Silvia; McKenzie, Kevin; Tenet, Vanessa; Njoroge, Julia; Rana, Farzana S.; Sakr, Samah R.; Snijders, Peter J. F.; Chung, Michael H.

2014-01-01

Objective To assess residual cervical intraepithelial neoplasia (CIN) 2/3 disease and clearance of high-risk (hr) human papillomavirus (HPV) infections at 6 months after cryotherapy among HIV-positive women. Design Follow-up study. Methods 79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy) and after cryotherapy (cells). Results At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI): 66.4–85.9). 18 women (22.8%) had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART) were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2–15.0) among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9–70). The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively. Conclusions Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity. PMID:25343563

Parity as a cofactor for high-grade cervical disease among women with persistent human papillomavirus infection

DEFF Research Database (Denmark)

Jensen, K E; Schmiedel, S; Norrild, B

2013-01-01

BACKGROUND:Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent...... human papillomavirus (HPV) infection.METHODS:A population-based cohort of women participated in a personal interview and underwent a gynaecological examination at which cervical specimens were obtained for HPV DNA testing. Follow-up information (~13 years) on cervical lesions was obtained from...

Next Generation Sequencing of Tubal Intraepithelial Carcinomas

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McDaniel, Andrew S.; Stall, Jennifer N.; Hovelson, Daniel H.; Cani, Andi K.; Liu, Chia-Jen; Tomlins, Scott A.; Cho, Kathleen R.

2016-01-01

Importance High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs or more specifically STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking. Observations We performed targeted next generation sequencing (NGS) on formalin-fixed, paraffin- embedded tissue from four women, two with HGSC and two with uterine endometrioid carcinoma (UEC) who were diagnosed with synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal relationship between these lesions. NGS confirmed the presence of a STIC clonally unrelated to one case of UEC. NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC. Conclusions and Relevance We demonstrate that targeted NGS can identify genetic lesions in minute lesions such as TICs, and confirm TP53 mutations as early driving events for HGSC. NGS also demonstrated unexpected relationships between presumed STICs and synchronous carcinomas, suggesting potential diagnostic and translational research applications. PMID:26181193

Next-Generation Sequencing of Tubal Intraepithelial Carcinomas.

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McDaniel, Andrew S; Stall, Jennifer N; Hovelson, Daniel H; Cani, Andi K; Liu, Chia-Jen; Tomlins, Scott A; Cho, Kathleen R

2015-11-01

High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs, or more specifically, STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking. We performed targeted next-generation sequencing (NGS) on formalin-fixed, paraffin-embedded tissue from 4 women, 2 with HGSC and 2 with uterine endometrioid carcinoma (UEC) who were diagnosed as having synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal association between these lesions. Next-generation sequencing confirmed the presence of a STIC clonally unrelated to 1 case of UEC, and NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC. We demonstrate that targeted NGS can identify genetic alterations in minute lesions, such as TICs, and confirm TP53 mutations as early driving events for HGSC. Next-generation sequencing also demonstrated unexpected associations between presumed STICs and synchronous carcinomas, providing evidence that some TICs are actually metastases rather than HGSC precursors.

Radio(chemo)therapy of the anal carcinoma. A retrospective study

International Nuclear Information System (INIS)

Sauer, Thomas Albert

2013-01-01

In a retrospective study the data of a consecutive cohort of 138 patients with a locally advanced squamous cell anal cancer were analysed, who were treated with a radio(chemo)therapy in the period from 1988 to 2011. The 5-year overall survival rate was 82%±4%. T category, UICC clinical stage, histopathologic grading and the ECOG performance status were significantly associated with overall survival. Acute toxicity grade 3/4 and chronic side effects grade 3 were found in 58% and 37% of the patients, respectively.

Changes in the Extracellular Matrix Are Associated With the Development of Serous Tubal Intraepithelial Carcinoma Into High-Grade Serous Carcinoma

NARCIS (Netherlands)

Steen, S.C.H.A. van der; Bulten, J.; Vijver, K.K. Van de; Kuppevelt, T.H. van; Massuger, L.F.

2017-01-01

OBJECTIVE: The identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of

Anal acoustic reflectometry

DEFF Research Database (Denmark)

Mitchell, Peter J; Klarskov, Niels; Telford, Karen J

2011-01-01

Anal acoustic reflectometry is a new technique of assessing anal sphincter function. Five new variables reflecting anal canal function are measured: the opening and closing pressure, the opening and closing elastance, and hysteresis.......Anal acoustic reflectometry is a new technique of assessing anal sphincter function. Five new variables reflecting anal canal function are measured: the opening and closing pressure, the opening and closing elastance, and hysteresis....

Endosonographic and manometric assessment of the anal sphincters after ileal pouch-anal anastomosis

International Nuclear Information System (INIS)

Sudol-Szopinska, I.; Jakubowski, W.; Ciesielski, A.; Bielecki, K.; Baczuk, L.; Tarnowski, W.

2003-01-01

Background. The aim of this study was to compare endosonography and manometry of the anal sphincters in patients after ileal pouch-anal anastomosis (IPAA). Patients and methods. Ten patients aged between 23 and 50 years with IPAA performed for ulcerative colitis were examined with anal endosonography (AES) and manometry. Results. AES visualised abnormal image of the internal anal sphincter (IAS) in 9 patients (90%). Defects of the external anal sphincter (EAS) and puborectalis muscle (PR) were shown in 4 patients (40%). In 5 patients (50%) correlation between endosonographic and manometric assessment for the all analysed muscles: IAS, EAS and PR was found. In 4 cases (40%) both methods correlated with the evaluation of the EAS only and in 1 patient (10%) no correlation was found. Correlation between both methods for the IAS was found in half of the patients (50%) while in the evaluation of the EAS and PR dynamic activity, it was found in 9 cases (90%). Conclusions. Anal endosonography and manometry allow us to assess the morphology as well as the function of the anal sphincters in patients with IPAA. The methods mentioned above show high correlation in the assessment of the EAS function (9 cases; 90%) whereas in the case of IAS, manometry frequently (5 patients; 50%) does not confirm endosonografically detected defects. (author)

Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: Subtle Features Not to Be Missed.

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Schwock, Joerg; Ko, Hyang Mi; Dubé, Valérie; Rouzbahman, Marjan; Cesari, Matthew; Ghorab, Zeina; Geddie, William R

2016-01-01

Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant lesion of the uterine cervix. A detailed examination of preinvasive SMILE cases including a comparison of the cytologic features with usual-type adenocarcinoma in situ (AIS) and human papillomavirus (HPV) genotyping was performed. Excisions and preceding Papanicolaou (Pap) tests were retrieved from the files of 2 tertiary care centers. Histologic review estimated the lesional SMILE proportion. Pap tests were reviewed and assessed for architectural, cellular and background features. Cobas® HPV test was performed. 13 cases were identified. Mean/median patient age was 35/33 years (range 23-51 years). Concurrent high-grade squamous intraepithelial lesion was found in 10/13 (77%) and AIS in 8/13 (62%) cases. In 6 cases, SMILE was dominant (≥50%) and represented in 5/6 corresponding Pap tests. Cytology interpretations differed more often in the SMILE-dominant group (p < 0.05). SMILE and AIS had overlapping features. Feathering and prominent nucleoli were absent in SMILE. HPV DNA was detected in all 12 cases tested. HPV 18 was most common (7/12). Excisions with positive/suspicious margins were reported in 5/6 SMILE-dominant versus 3/7 nondominant cases. SMILE is best considered as an AIS variant for cytologic, etiologic and management purposes. Cytologic features overlap with AIS, but are more subtle and easily missed. HPV testing may play a role in facilitating SMILE detection. © 2016 S. Karger AG, Basel.

Highly differentiated keratinizing squamous cell cancer of the cervix: a rare, locally aggressive tumor not associated with human papillomavirus or squamous intraepithelial lesions.

Science.gov (United States)

Morrison, C; Catania, F; Wakely, P; Nuovo, G J

2001-10-01

The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening.

High Prevalence of Anal Human Papillomavirus-Associated Cancer Precursors in a Contemporary Cohort of Asymptomatic HIV-Infected Women.

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Heard, Isabelle; Etienney, Isabelle; Potard, Valérie; Poizot-Martin, Isabelle; Moore, Catherine; Lesage, Anne-Carole; Ressiot, Emmanuelle; Crenn-Hebert, Catherine; Fléjou, Jean-François; Cubie, Heather; Costagliola, Dominique; Darragh, Teresa M

2015-05-15

Although human immunodeficiency virus (HIV)-infected women are at high risk for anal cancer, few data have been published on prevalence of and risk factors for anal precancer and potential screening strategies in this risk group. A cross-sectional anal screening study was nested in a gynecological cohort of HIV-infected women. Anal swab specimens were collected for cytology and human papillomavirus (HPV) testing. High-resolution anoscopy, with biopsy when indicated, was systematically performed. Among the 171 enrolled women, median age was 47.3 years and 98% were receiving combination antiretroviral therapy. Median CD4(+) count was 655 cells/µL and HIV load was associated with increased risk of HG-AIN+. Abnormal anal cytology and HPV-16 infection performed best as a screening strategy for HG-AIN+ histology, with positive likelihood ratios of 3.4 (95% CI, 2.3-5.1) and 4.7 (95% CI, 2.5-8.7) and negative likelihood ratios of 0.2 (95% CI, .07-.8) and 0.4 (95% CI, .2-.9), respectively. HIV-infected women with a history of HPV-associated cervical disease are at increased risk for HG-AIN+ and should be offered anal cancer screening. Anal cytology and HPV-16 genotyping had the best screening performance. Anal cytology is easy to perform routinely; it may be the best candidate for screening for HG-AIN among HIV-infected women. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Chronic anal fissure: morphometric analysis of the anal canal at 3.0 Tesla MR imaging.

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Erden, Ayşe; Peker, Elif; Gençtürk, Zeynep Bıyıklı

2017-02-01

OBJECTıVE: To compare the morphometric data relating to the muscular structures of the anal canal, in patients with chronic anal fissure and in control group, examined at a 3.0 Tesla MR system. Forty-seven consecutive patients with chronic anal fissure and randomly selected 40 patients who had no claims for perianal disease during their life time were included in the study. T2-weighted sagittal, high-resolution (HR) T2-weighted, and contrast-enhanced fat-suppressed T1-weighted oblique axial and oblique coronal images were retrospectively analyzed by two observers in consensus. Thickness of sphincteric muscles, anal canal length, anorectal angle, thickness of anococcygeal ligament, depth of Minor triangle, width between subcutaneous sphincters, vascularity of posterior commissure, visibility of posterosuperior projection of external sphincter, and angle between the distal anal canal and posterosuperior projection of external sphincter (H angle) in patients and in controls were compared and analyzed using t test, Mann-Whitney U test, and Spearman correlation. The patients with chronic anal fissure had longer anal canal (51.50 mm ± 0.91 vs. 44.11 mm ± 0.71; p = 0.000), thicker internal anal sphincter muscle at mid-anal level (4.18 ± 0.15 vs. 3.39 ± 0.07; p = 0.007), and wider space between subcutaneous external sphincters (11.39 ± 0.50 vs. 6.89 ± 0.22; p = 0.000). In patients, there was a positive correlation between H angle and external sphincter thickness at proximal (r = 0.347; p = 0.021), middle (r = 0427; p = 0.000), and distal (r = 0.518; p = 0.000)) levels of the anal canal. CONCLUSıON: 3.0 Tesla MR imaging provides detailed information about the morphometric changes in the anal sphincter muscles in patients with chronic anal fissure.

A randomized clinical trial comparing cervical dysplasia treatment with cryotherapy vs loop electrosurgical excision procedure in HIV-seropositive women from Johannesburg, South Africa.

Science.gov (United States)

Smith, Jennifer S; Sanusi, Busola; Swarts, Avril; Faesen, Mark; Levin, Simon; Goeieman, Bridgette; Ramotshela, Sibongile; Rakhombe, Ntombiyenkosi; Williamson, Anna L; Michelow, Pam; Omar, Tanvier; Hudgens, Michael G; Firnhaber, Cynthia

2017-08-01

Mortality associated with cervical cancer is a public health concern for women, particularly in HIV-seropositive women in resource-limited countries. HIV-seropositive women are at a higher risk of high-grade cervical precancer, which can eventually progress to invasive carcinoma as compared to HIV-seronegative women. It is imperative to identify effective treatment methods for high-grade cervical precursors among HIV-seropositive women. Randomized controlled trial data are needed comparing cryotherapy vs loop electrosurgical excision procedure treatment efficacy in HIV-seropositive women. Our primary aim was to compare the difference in the efficacy of loop electrosurgical excision procedure vs cryotherapy for the treatment of high-grade cervical intraepithelial neoplasia (grade ≥2) among HIV-seropositive women by conducting a randomized clinical trial. HIV-seropositive women (n = 166) aged 18-65 years with histology-proven cervical intraepithelial neoplasia grade ≥2 were randomized (1:1) to cryotherapy or loop electrosurgical excision procedure treatment at a government hospital in Johannesburg. Treatment efficacy was compared using 6- and 12-month cumulative incidence posttreatment of: (1) cervical intraepithelial neoplasia grade ≥2; (2) secondary endpoints of histologic cervical intraepithelial neoplasia grade ≥3 and grade ≥1; and (3) high-grade and low-grade cervical cytology. The study was registered (ClinicalTrials.govNCT01723956). From January 2010 through August 2014, 166 participants were randomized (86 loop electrosurgical excision procedure; 80 cryotherapy). Cumulative cervical intraepithelial neoplasia grade ≥2 incidence was higher for cryotherapy (24.3%; 95% confidence interval, 16.1-35.8) than loop electrosurgical excision procedure at 6 months (10.8%; 95% confidence interval, 5.7-19.8) (P = .02), although by 12 months, the difference was not significant (27.2%; 95% confidence interval, 18.5-38.9 vs 18.5%; 95% confidence interval, 11

Prevalence and risk factors for cervical intraepithelial neoplasia in HIV-infected women in Salvador, Bahia, Brazil

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Paula Matos Oliveira

Full Text Available CONTEXT AND OBJECTIVE: The human immunodeficiency virus (HIV is frequently associated with high-grade intraepithelial neoplasia. Immunosuppression and high HIV viral load are the main risk factors for cervical intraepithelial neoplasia (CIN. The aim of this study was to determine the prevalence of CIN in HIV-infected women in Salvador, Bahia, Brazil, and to describe the risk factors in comparison with non-infected women. DESIGN AND SETTING: Cross-sectional study at the AIDS Reference Center of Bahia and the Gynecological Outpatient Clinic of Fundação Bahiana para o Desenvolvimento da Ciência, in Salvador, Bahia, Brazil. METHODS: Sixty-four HIV-infected women and 76 uninfected women from Salvador were enrolled between May 2006 and May 2007. Associations between CIN and presence of HIV infection, HIV viral load, proportion of T CD4+ lymphocytes and risk factors were evaluated. The independence of the risk factors was investigated using logistic regression. RESULTS: CIN was more prevalent among HIV-infected women than in the control group (26.6% versus 6.6%; P = 0.01. The odds ratio for CIN among HIV-infected women was 3.7 (95% confidence interval, CI: 1.23-11; P = 0.01, after adjusting for the following variables: age at first sexual intercourse, number of partners, number of deliveries and previous history of sexually transmitted disease. CONCLUSION: The prevalence of CIN among HIV-infected women was significantly higher than among women without HIV infection. HIV infection was the most important risk factor associated with the development of cervical lesions.

Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia.

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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.

Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix

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Gupta Ruchi

2010-01-01

Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC which has not been reported in the Indian population previously. Materials and Methods: Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12. Statistical Analysis: For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe. Results: p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20. There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20% showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001. Conclusions: p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.

High-resolution anoscopy: Unchartered territory for gastroenterologists?

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Albuquerque, Andreia

2015-09-25

High-resolution anoscopy (HRA) is a procedure where patients with an increased risk of anal cancer, like men who have sex with men, human immunodeficiency virus infected individuals, transplant patients and women with a history of lower genital tract neoplasia, with abnormal anal cytology results, are submitted to anal and perianal visualization under magnification. This will allow for a better detection of anal high-grade lesions that can be treated, in an effort to prevent anal cancer. Anal cancer screening follows the same principles that cervical cancer screening. During this procedure, an anoscope is inserted and a colposcope is used to examine systematically the squamocolumnar junction, the transformation zone and the perianal skin. Initially the observation is done with no staining and then with the application of acetic acid and Lugol's iodine solution, allowing for better lesion identification and characterization. Any suspicious lesion seen should be carefully evaluated and biopsied. Without HRA only a small percentage of suspicious lesions are identified. High-grade lesions that are detected can be ablated under HRA. This is a challenging exam to perform, with a long learning curve and the number of clinicians performing it is limited, although the growing number of patients that need to been screened. Specific equipment is required, with these patients ideally been followed by a multidisciplinary team, in a reference centre. HRA remains unfamiliar for many gastroenterologists.

Risk factors of recurrent anal sphincter ruptures

DEFF Research Database (Denmark)

Jangö, Hanna; Langhoff-Roos, J; Rosthøj, Steen

2012-01-01

Please cite this paper as: Jangö H, Langhoff-Roos J, Rosthøj S, Sakse A. Risk factors of recurrent anal sphincter ruptures: a population-based cohort study. BJOG 2012;00:000-000 DOI: 10.1111/j.1471-0528.2012.03486.x. Objective  To determine the incidence and risk factors of recurrent anal sphincter...... were used to determine risk factors of recurrent ASR. Main outcome measures  The incidence of recurrent ASR and odds ratios for possible risk factors of recurrent ASR: age, body mass index, grade of ASR, birthweight, head circumference, gestational age, presentation, induction of labour, oxytocin...... augmentation, epidural, episiotomy, vacuum extraction, forceps, shoulder dystocia, delivery interval and year of second delivery. Results  Out of 159 446 women, 7336 (4.6%) experienced an ASR at first delivery, and 521 (7.1%) had a recurrent ASR (OR 5.91). The risk factors of recurrent ASR in the multivariate...

Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an eastern cooperative oncology group study

International Nuclear Information System (INIS)

Martenson, James A.; Lipsitz, Stuart R.; Wagner, Henry; Kaplan, Edward H.; Otteman, Larry A.; Schuchter, Lynn M.; Mansour, Edward G.; Talamonti, Mark S.; Benson, Al Bowen

1996-01-01

Purpose: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. Methods and Materials: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m 2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m 2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. Results: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. Conclusion: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm

MRI differentiation of low-grade from high-grade appendicular chondrosarcoma

International Nuclear Information System (INIS)

Douis, Hassan; Singh, Leanne; Saifuddin, Asif

2014-01-01

To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. (orig.)

MRI differentiation of low-grade from high-grade appendicular chondrosarcoma

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Douis, Hassan; Singh, Leanne; Saifuddin, Asif [The Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom)

2014-01-15

To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. (orig.)

A Mouse Model for Human Anal Cancer

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Stelzer, Marie K.; Pitot, Henry C.; Liem, Amy; Schweizer, Johannes; Mahoney, Charles; Lambert, Paul F.

2010-01-01

Human anal cancers are associated with high-risk human papillomaviruses (HPVs) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including but not limited to their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors; whereas, none of the like treated non-transgenic mice showed tumors. Histopathological analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. PMID:20947489

Anal fissure - series (image)

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Anal fissures are tears in the skin overlying the anal sphincter, usually due to increased tone of the anal sphincter muscles, and a failure of these muscle to relax. Anal fissures cause pain during defecation and bleeding from the anus.

Evaluation of radiotherapy and chemoradiotherapy for anal canal epidermoid cancer in our center

International Nuclear Information System (INIS)

Obara, Kunihiko; Sahara, Rikisaburo; Yamana, Tetsuro; Okamoto, Kinya; Takahashi, Tomoko; Furukawa, Satomi; Okada, Daisuke; Kaneko, Yasushi; Matsumoto, Atsuo

2008-01-01

The efficacy and safety of radiotherapy (RT) and chemoradiotherapy (CRT) for anal canal epidermoid cancer were evaluated. Twenty-four patients with anal canal epidermoid cancer were treated in our center between 1988 and 2006, consisting of 13 patients treated by RT and 11 by CRT. In these patients, the efficacy and safety of RT and CRT were evaluated in terms of adverse events, 5-year local control rates, 5-year disease-free survival rates, and 5-year survival rates. No grade 3 or higher adverse events were noted in patients receiving RT. In contrast, anorexia, diarrhea, neutropenia, and anemia were observed in 33.3%, 10%, 33.3%, and 10%, respectively, of the patients receiving CRT. The anal preserving rate, 5-year local control rate, 5-year disease-free survival rate, and 5-year survival rate were 66.7%, 73%, 77.5%, and 88.4%, respectively. RT and CRT for anal canal epidermoid cancer should be first-line treatments because of their safety and efficacy. (author)

Anal sphincter electromyography in patients with Anorectal Dysfunctions

International Nuclear Information System (INIS)

Trinchet Soler, Rafael; Hidalgo Marrero, Yanet; Espichicoque Megret, Arianne; Manzano Suarez, Jianeya; Perez Gonzales, Ruth Maite

2009-01-01

The purpose of this work is to evaluate the electromyography value of anal sphincter in patients with anorectal dysfunctions. Anorectal dysfunctions are frequent reason of pediatric consultation in children, especially with anal incontinence. A study of series of cases in patient with anorectal dysfunctions was carried out from January 2002 to January of 2006. 65 patients were studied. Anorectal malformations (ARM) represented the predominant affection with 38 patients (58.5%), prevailing the male sex in 25 patients (65.8%). Encopresis and intestinal agagliosis dicrease was observed. Sphincter was found before surgical treatment through electromyography in patients with anorectal malformations and colostomy; in those with definitive operation and open colostomy, it avoided the operation in a patient that did not have muscular activity of the external sphincter. In children already operated and with closed colostomy several electromyography changes were observed in correspondence with different incontinence grades. In encopresis cases the study was useful to rule out sphincter functional alterations. Electromyography was pathological in all the operated patients of intestinal aganglionosis. This procedure was very useful for anal incontinence study that helped to determine and establish the prognosis. (author)

IMPORTANCE OF THE ANAL MANOMETRY IN THE JUDICIALMEDICAL EXPERTISE OF THE ANAL PENETRATION

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Jelica Miljkovic

2001-11-01

Full Text Available The forceful anal penetration can leave as a consequence a lasting damage ofthe anal sphincter function. The anal manometry is one of the methods that, in anindirect way, by measuring the pressure in the anal channel, may determine theexistence of the anus-closing muscles' function damage. The importance of the analmanometry application as an objective indicator of a possible damage of the analsphincter function is presented in the cases of the judicial-medical expertise of theanal penetration. Three cases of criminal acts of sexual abuse and rape in which thejudicial-medical expertise by the anal manometry method was applied are analyzed.The anal manometry method is reliable in determining the functional stote of theexternal and the internal anal sphincter and it should be accepted as obligatory indiagnostics and verification of the anal penetration.

Epidemiology of anal HPV infection in high-risk men attending a sexually transmitted infection clinic in Puerto Rico.

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Vivian Colón-López

Full Text Available Recent studies in Puerto Rico have reported an increasing incidence of anal cancer in Puerto Rican men. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among men attending an STI clinic in Puerto Rico.We conducted a cross-sectional study among 205 men 18 years and older. A comprehensive survey was administered that included a demographic and a behavioral assessment. Separate logistic regression models were performed to determine factors associated with any, high-risk (HR, and multiple anal HPV infection.The mean age of the study sample was 38.0±13.5 years. The most common HR types were 58, 51 and 31. Overall, HR anal HPV infection was found in 53.5% of the participants. Multiple HPV types in the anal canal were found in 47.6% of the sample. A third (29.8% of participants reported being men who had sex with men (MSM. MSM had a significantly higher prevalence of any, HR and multiple HPV infection (p-value<0.05. Separate multivariate logistic regression analyses showed that being MSM was associated with any (OR = 4.5; [95%CI: 1.9-10.7], HR (OR = 3.4; [95%CI: 1.1-10.3 and multiple anal HPV infection (OR = 3.6; [95%CI: 1.5-9.1. HIV was marginally associated with multiple anal HPV infection in multivariate analysis (OR = 3.3; 95%CI = 1.0-11.0.Anal HPV is common among sexually active men attending this STI clinic, with higher likelihood of anal HPV infection among MSM.

Prevalence of anal infection due to high-risk human papillomavirus and analysis of E2 gene integrity among women with cervical abnormalities.

Science.gov (United States)

Gonzalez-Losa, María Del Refugio; Puerto-Solís, Marylin; Ayora-Talavera, Guadalupe; Gómez-Carvallo, Jesús; Euán-López, Alejandra; Cisneros-Cutz, José I; Rosado-López, Ariel; Echeverría Salazar, Jesúa; Conde-Ferráez, Laura

2018-04-01

High-risk human papillomaviruses (HR-HPV) infection has been associated with 90% of anal cancer cases. Women with abnormal cytology are a high-risk group to develop anal neoplasia. The aim of this study is to describe the prevalence and epidemiology of HR-HPV 16, 18, 45, and 58 anal infections in women with cervical abnormalities, as well as to assess E2 gene integrity. A cross-sectional study was performed on 311 cervical and 311 anal samples from patients with abnormal cytology in two colposcopy clinics in Yucatan, Mexico. A specific PCR for oncogenes was performed in order to identify HVP 16, 18, 45 and 58. Real time PCR was used to amplify the whole HPV 16, 18, and 58 E2 gene to verify its integrity in anal samples. High risk HPV 16, 18, 58, and/or 45 were found in 41.47% (129/311) of cervical samples, and in 30.8% (96/331) of anal samples, with 18% (57/311) of the patients being positive in both samples. The same genotypes in both anatomical sites were observed in 11.25% (35/311). The E2 gene was disrupted in 82% of all tested samples. The frequency of genome disruption viral integration in anal samples by genotype was: HPV 58 (97.2%); HPV 16 (72.4%), and HPV 18 (0%). Women with cervical disease have HR-HPV anal infections, and most of them have the E2 gene disrupted, which represents a risk to develop anal cancer. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

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Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Myerson, Robert J. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Goodyear, Michael D. [Department of Medicine, Dalhousie University, Halifax (Canada); Willins, John [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Esthappan, Jacqueline [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Rotman, Marvin [Department of Radiation Oncology, State University of New York—Downstate Medical Center, Brooklyn, New York (United States); Parikh, Parag J. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Safran, Howard [Department of Medicine, Brown University, Providence, Rhode Island (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)

2013-05-01

Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

THE 3-GROUP METAPHASE AS A MORPHOLOGIC INDICATOR OF HIGH-PLOIDY CELLS IN CERVICAL INTRAEPITHELIAL NEOPLASIA

NARCIS (Netherlands)

PIETERS, WJLM; KOUDSTAAL, J; PLOEMZAAYER, JJ; Janssens, J; OOSTERHUIS, JW

There is a need for additional morphologic criteria to improve the value of histologic classification for the prediction of the biologic behavior of cervical intraepithelial neoplasia (CIN). Representative slides from 72 cone specimens containing CIN were examined to study the correlation between

Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico

Science.gov (United States)

López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

2009-01-01

Background In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Results Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. Conclusion We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype. PMID:19216802

Peripheral Leukocytosis Is Inversely Correlated with Intratumoral CD8+ T-Cell Infiltration and Associated with Worse Outcome after Chemoradiotherapy in Anal Cancer

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Daniel Martin

2017-09-01

Full Text Available Peripheral blood leukocytosis has been implicated in promoting tumor progression leading to worse survival, but the mechanisms behind this phenomenon remain unexplored. Here, we examined the prognostic role of pretreatment white blood cell (WBC count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL and myeloperoxidase+ tumor-associated neutrophils (TANs in patients with anal squamous cell carcinoma (ASCC treated with definitive chemoradiotherapy (CRT. After a median follow-up of 26 months, leukocytosis correlated with advanced T-stage (p < 0.001 and N-stage (p < 0.001, and predicted for worse distant-metastasis-free survival (p = 0.006, disease-free-survival (DFS, p = 0.029, and overall survival (p = 0.013. Importantly, leukocytosis was associated with a lower intraepithelial CD8+ TIL density (p = 0.014, whereas low CD8+ TIL expression in the intraepithelial compartment was associated with worse DFS (p = 0.028. Additionally, high TAN expression in the peritumoral compartment was associated with a significantly lower density of CD8+ TIL (p = 0.039, albeit, TAN expression lacked prognostic value. In conclusion, leukocytosis constitutes an important prognostic marker in ASCC patients treated with CRT. In conjunction with intratumoral TIL and TAN, these data provide for the first time important insight on the correlation of peripheral blood leukocytosis with the intratumoral immune contexture and could be relevant for future patient stratification using immunotherapies in ASCC.

Persistence and reappearance of high-risk human papillomavirus after conization

DEFF Research Database (Denmark)

Gosvig, Camilla Flarup; Huusom, Lene Drasbek; Andersen, Klaus Kaae

2013-01-01

Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development...

Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin?

Science.gov (United States)

Gao, Faye F; Bhargava, Rohit; Yang, Huaitao; Li, Zaibo; Zhao, Chengquan

2013-08-01

In the past several decades, the concept of serous ovarian carcinoma has been revised repeatedly. However, the exact pathogenesis remains controversial. The most popular current concept is origin from the epithelium of the fimbriated ends of the fallopian tubes. The objective of our study was to evaluate the characteristic clinical and morphologic features of serous tubal intraepithelial carcinoma (STIC) and associated invasive carcinomas. One hundred sixteen consecutive cases of STIC seen from 2007 to 2011 were included in this study. High-grade serous carcinoma (HGSC) with or without a mixed component was identified in 107 cases (92.2%), non-HGSC in 5 cases, and STICs without invasive carcinoma in 4 cases. Using conventional criteria, HGSCs were classified as fallopian tube in origin in 65 cases (60.7%), as ovarian in 30 (28.0%), as peritoneal in 9 (8.4%), and as endometrial in 3 (2.8%). Among the 107 cases with HGSCs, most STICs (86; 80%) were present unilaterally, whereas invasive tumors more commonly involved the ovaries bilaterally (79%; 84 cases). These findings support the hypothesis that STIC acts as a precursor lesion for most fallopian tube, ovarian, and peritoneal HGSCs, but not for endometrial HGSC. Copyright © 2013 Elsevier Inc. All rights reserved.

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

Science.gov (United States)

Sjøborg, Katrine D.; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G. Cecilie; Jonassen, Christine M.

2012-01-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. PMID:22518869

Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review

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Marcelo Corti

2012-12-01

Full Text Available Squamous anal cell carcinoma is a rare malignancy that represents the 1.5% to 2% of all the lower digestive tract cancers. However, an increased incidence of invasive anal carcinoma is observed in HIV-seropositive population since the widespread of highly active antiretroviral therapy. Human papillomavirus is strongly associated with the pathogenesis of anal cancer. Anal intercourse and a high number of sexual partners appear to be risk factors to develop anal cancer in both sexes. Anal pain, bleeding and a palpable lesion in the anal canal are the most common clinical features. Endo-anal ultrasound is the best diagnosis method to evaluate the tumor size, the tumor extension and the infiltration of the sphincter muscle complex. Chemoradiotherapy plus antiretroviral therapy are the recommended treatments for all stages of localized squamous cell carcinoma of the anal canal in HIV-seropositive patients because of its high rate of cure. Here we present an HIV patient who developed a carcinoma of the anal canal after a long time of HIV infection under highly active antiretroviral therapy with a good virological and immunological response.

Anal intraepitelial neoplasia: a narrative review

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Garazi Elorza

2016-01-01

Full Text Available Anal intraepitelial neoplasia (AIN constitutes a major health problem in certain risk groups, such as patients with immunosuppression of varied origin, males who have sexual relations with other males, and females with a previous history of vaginal or cervical abnormalities in cytology. Its relationship with the human papillomavirus (HPV infection has been well documented; however, many of the factors involved in the progression and regression of the viral infection to dysplasia and anal carcinoma are unknown. AIN can be diagnosed through cytology of the anal canal or biopsy guided by high-resolution anoscopy. However, the need for these techniques in high-risk groups remains controversial. Treatment depends on the risk factors and given the high morbidity and high recurrence rates the utility of the different local treatments is still a subject of debate. Surgical biopsy is justified only in the case of progression suggesting lesions. The role of the vaccination in high-risk patients as primary prevention has been debated by different groups. However, there is no general consensus on its use or on the need for screening this population.

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.

Science.gov (United States)

Ibáñez, Raquel; Moreno-Crespi, Judit; Sardà, Montserrat; Autonell, Josefina; Fibla, Montserrat; Gutiérrez, Cristina; Lloveras, Belen; Alejo, María; Català, Isabel; Alameda, Francesc; Casas, Miquel; Bosch, F Xavier; de Sanjosé, Silvia

2012-01-26

A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US. During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions--HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2

Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era.

Science.gov (United States)

Benard, Vicki B; Castle, Philip E; Jenison, Steven A; Hunt, William C; Kim, Jane J; Cuzick, Jack; Lee, Ji-Hyun; Du, Ruofei; Robertson, Michael; Norville, Scott; Wheeler, Cosette M

2017-06-01

A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P = .02). Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series.

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Morrison, Jane C; Blanco, Luis Z; Vang, Russell; Ronnett, Brigitte M

2015-04-01

A precursor for invasive ovarian/pelvic high-grade serous carcinoma, termed serous tubal intraepithelial carcinoma (STIC), has been identified and characterized through careful analysis of the fallopian tubes in both prophylactic salpingo-oophorectomy specimens obtained from women with either a family history of breast and/or ovarian cancer or germline mutations of BRCA1 and BRCA2 and in cases of pelvic high-grade serous carcinoma. Data on incidental STICs and clinically occult microscopic invasive high-grade serous carcinomas are limited. We analyzed the clinicopathologic features of 22 cases, including 15 pure STICs and 7 STICs associated with microscopic invasive high-grade serous carcinomas, identified incidentally in fallopian tubes removed for nonprophylactic indications. Patient age ranged from 39 to 79 years (mean: 62.7; median: 61), with only 1 patient under the age of 50. No patients were known to carry BRCA1 or BRCA2 mutations. Of the 12 pure STICs for which the location in the fallopian tube could be established, 9 were in the fimbriated portion, 1 was at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. Of the 7 STICs with associated invasive high-grade serous carcinoma, 3 were located in the fimbriated portion, 2 were at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. The invasive components were in the fallopian tube in 6 cases, 4 in subepithelial stroma of tubal mucosa, and 2 as an intramucosal (exophytic) luminal lesion without invasion of underlying subepithelial stroma (size range: 1 to 4 mm). The remaining case had a microscopic focus of high-grade serous carcinoma within the ipsilateral ovary (1.3 mm cortical focus) identified only on deeper sections, without an associated invasive component in the fallopian tube. The preferential finding of atypical epithelium with the cytologic features of high-grade serous carcinoma, namely STIC, in the fallopian tubes rather than the

Frequency of cervical intraepithelial neoplasia treatment in a well-screened population

DEFF Research Database (Denmark)

Barken, Sidsel Svennekjaer; Rebolj, Matejka; Andersen, Erik Søgaard

2012-01-01

Treatment of cervical intraepithelial neoplasia (CIN) detectable at screening has helped reduce the incidence of cervical cancer, but has also led to overtreatment. The estimates of overtreatment have often focused on a particular grade of CIN or age group. The aim of this paper was to provide...... a nationwide population-based estimate of the frequency of CIN treatment per prevented cervical cancer case in a well-screened population. We retrieved the data from the Danish National Population, Patient, Health Insurance, Pathology, and Cancer Registers, and calculated annual age-standardized CIN treatment...... rates. We estimated the frequency of CIN treatment per prevented cervical cancer case by comparing the cumulative life-time risk of CIN treatment from 1996 onward, with the difference in the cumulative life-time risks of cervical cancer in the prescreening and the screening periods. Since 1996, more...

Anal incontinence after two vaginal deliveries without obstetric anal sphincter rupture

DEFF Research Database (Denmark)

Persson, Lisa K G; Sakse, Abelone; Langhoff-Roos, Jens

2017-01-01

PURPOSE: To evaluate prevalence and risk factors for long-term anal incontinence in women with two prior vaginal deliveries without obstetric anal sphincter injury (OASIS) and to assess the impact of anal incontinence-related symptoms on quality of life. METHODS: This is a nation-wide cross......-sectional survey study. One thousand women who had a first vaginal delivery and a subsequent delivery, both without OASIS, between 1997 and 2008 in Denmark were identified in the Danish Medical Birth Registry. Women with more than two deliveries in total till 2012 were excluded at this stage. Of the 1000 women...... affected their quality of life. No maternal or obstetric factors including episiotomy and vacuum extraction were consistently associated with altered risk of anal incontinence in the multivariable analyses. CONCLUSIONS: Anal incontinence and fecal urgency is reported by one fifth of women with two vaginal...

Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

Directory of Open Access Journals (Sweden)

Katy Milne

Full Text Available BACKGROUND: Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC, but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases and myeloperoxidase (negative association in clear cell cases. CONCLUSIONS/SIGNIFICANCE: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.

Anal Cancer—Patient Version

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Anal cancer cases have been increasing over several decades. Infection with human papillomavirus (HPV) is the major risk factor for anal cancer. Start here to find information on anal cancer treatment, causes and prevention, research, and statistics.

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

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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.

Genotyping of the human papilloma virus in a group of Mexican women treated in a highly specialist hospital: Multiple infections and their potential transcendence in the current vaccination programme.

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Romero-Morelos, Pablo; Uribe-Jiménez, Arizbett; Bandala, Cindy; Poot-Vélez, Albros; Ornelas-Corral, Nora; Rodríguez-Esquivel, Miriam; Valdespino-Zavala, Mariana; Taniguchi, Keiko; Marrero-Rodríguez, Daniel; López-Romero, Ricardo; Salcedo, Mauricio

2017-10-11

Human papilloma virus (HPV) is one of the main risk factors associated with the development of cervical cancer and its precursor lesions. It has been reported that HPV16 and 18 types cover approximately 70% of cervical cancer worldwide; however, significant variation in percentages of HPV infections could be related to specific populations. Purified DNA of 67 cervical samples were analyzed by Linear Array® HPV genotyping kit. These analyzed samples correspond to 19 cervical tumors, 15 high-grade squamous intraepithelial lesions, 20 low-grade squamous intraepithelial lesions, and 13 cervical samples without injury were studied, all of them previously diagnosed. In general, 16 different HPV types were found with differences in their frequencies, cervical invasive cancer being the richest in HPV sequences, followed by the low-grade squamous intraepithelial lesions and then high-grade lesions. HPV16 was the most frequently distributed type in neoplastic lesions of the cervix, followed by the HPV52, suggesting viral type variability, probably associated to the geographical region studied. The results could indicate variability in HPV presence in Mexico, underlining the important role for HPV52 among others in the Mexican population. This would also potentially have an impact on the current anti-HPV vaccination schemes. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Anal Cancer—Health Professional Version

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Anal cancer is a rare malignancy and accounts for a small percentage of cancers of the lower alimentary tract. The most common type of anal cancer is squamous cell carcinoma in the anal canal. Find evidence-based information on anal cancer treatment, causes and prevention, research, and statistics.

Clinical, manometric, and ultrasonographic results of pneumatic balloon dilatation vs. lateral internal sphincterotomy for chronic anal fissure: a prospective, randomized, controlled trial.

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Renzi, Adolfo; Izzo, Domenico; Di Sarno, Giandomenico; Talento, Pasquale; Torelli, Francesco; Izzo, Giuseppe; Di Martino, Natale

2008-01-01

This prospective, randomized, controlled trial was designed to compare the clinical, functional, and morphologic results of pneumatic balloon dilatation with lateral internal sphincterotomy for the treatment of chronic anal fissure. All patients with symptomatic chronic anal fissure were randomly assigned to pneumatic balloon dilatation or lateral internal sphincterotomy and invited to complete a standardized questionnaire inquiring about their symptoms. Anal ultrasonography and anal manometry were performed before and six months after surgery. A proctologic examination was performed between the fifth and sixth postoperative weeks. Anal continence, scored by using a validated continence grading scale, was evaluated preoperatively at 1 and 6 weeks and at 12 and 24 months. Fifty-three patients, who satisfied selection criteria, were enrolled in the trial. Four patients (7.5 percent) were lost to follow-up. Twenty-four patients (11 males; mean age, 42 +/- 8.2 years) underwent pneumatic balloon dilatation and 25 patients (10 males; mean age, 44 +/- 7.3 years) underwent lateral internal sphincterotomy. Fissure-healing rates were 83.3 percent in the pneumatic balloon dilatation and 92 percent in the lateral internal sphincterotomy group. Recurrent anal fissure was observed in one patient (4 percent) after lateral internal sphincterotomy. At anal manometry, mean resting pressure decrements obtained after pneumatic balloon dilatation and lateral internal sphincterotomy were 30.5 and 34.3 percent, respectively. After pneumatic balloon dilatation, anal ultrasonography did not show any significant sphincter damage. At 24-month follow-up, the incidence of incontinence, irrespective of severity, was 0 percent in the pneumatic balloon dilatation group and 16 percent in the lateral internal sphincterotomy group (P < 0.0001). As lateral internal sphincterotomy, pneumatic balloon dilatation grants a high anal fissure-healing rate but with a statistically significant reduction in

High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men.

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Glick, Sara Nelson; Feng, Qinghua; Popov, Viorica; Koutsky, Laura A; Golden, Matthew R

2014-02-01

There are few published estimates of anal human papillomavirus (HPV) infection rates among young men who have sex with men (YMSM). We estimated incidence and prevalence of type-specific anal HPV infection using clinician-collected anal swabs for HPV DNA testing obtained during a 1-year prospective study of 94 YMSM (mean age, 21 years) in Seattle. Seventy percent of YMSM had any HPV infection detected during the study, and HPV-16 and/or -18 were detected in 37%. The incidence rate for any new HPV infection was 38.5 per 1000 person-months and 15.3 per 1000 person-months for HPV-16/18; 19% had persistent HPV-16/18 infection. No participant tested positive for all 4 HPV types in the quadrivalent vaccine. The number of lifetime male receptive anal sex partners was significantly associated with HPV infection. The prevalence of HPV-16/18 was 6% among YMSM with a history of 1 receptive anal sex partner and 31% among YMSM with ≥ 2 partners. Although the high prevalence of HPV among YMSM highlights the desirability of vaccinating all boys as a strategy to avert the morbidity of HPV infection, most YMSM appear to remain naive to either HPV-16 or -18 well into their sexual lives and would benefit from HPV immunization.

Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix.

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Aires, G M A; Meireles, J R C; Oliveira, P C; Oliveira, J L; Araújo, E L; Pires, B C; Cruz, E S A; Jesus, N F; Pereira, C A B; Cerqueira, E M M

2011-01-01

We evaluated micronucleus and apoptosis occurrence among women with normal smears and women with different kinds of cervical abnormalities, i.e., inflammatory processes and low- and high-grade squamous intraepithelial lesions (N = 12, N = 10 and N = 27, respectively). The sample included 59 women who were seen at a public medical service for cervical cancer prevention in Feira de Santana, Bahia, Brazil. The diagnosis was established by means of cytological, colposcopic, and histopathological examination. Cytogenetic analysis was performed on 2000 cells from each woman and included assessment of micronuclei and nuclear degenerative abnormalities indicative of apoptosis (karyorrhexis, pyknosis and condensed chromatin). Micronucleus frequency was significantly higher in the women with high-grade squamous intraepithelial lesions than in the women without cervical abnormalities or inflammatory processes (P 0.50), and significantly lower in women without cervical abnormalities and in women showing high-grade squamous intraepithelial lesions than in women showing inflammatory processes or low-grade squamous intraepithelial lesions (P cancer. The assessment of nuclear degenerative abnormalities indicative of apoptosis increased the sensitivity of this test.

High grade glioma: Imaging combined with pathological grade defines management and predicts prognosis

International Nuclear Information System (INIS)

Burnet, Neil G.; Lynch, Andrew G.; Jefferies, Sarah J.; Price, Stephen J.; Jones, Phil H.; Antoun, Nagui M.; Xuereb, John H.; Pohl, Ute

2007-01-01

Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. Patients and methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma

World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer.

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Santesso, Nancy; Mustafa, Reem A; Schünemann, Holger J; Arbyn, Marc; Blumenthal, Paul D; Cain, Joanna; Chirenje, Michael; Denny, Lynette; De Vuyst, Hugo; Eckert, Linda O'Neal; Forhan, Sara E; Franco, Eduardo L; Gage, Julia C; Garcia, Francisco; Herrero, Rolando; Jeronimo, José; Lu, Enriquito R; Luciani, Silvana; Quek, Swee Chong; Sankaranarayanan, Rengaswamy; Tsu, Vivien; Broutet, Nathalie

2016-03-01

It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries. Copyright © 2015. Published by Elsevier Ireland Ltd.

Anal incontinence in women with recurrent obstetric anal sphincter rupture

DEFF Research Database (Denmark)

Bøgeskov, Reneé; Nickelsen, Carsten Nahne Amtoft; Secher, Niels Jørgen

2015-01-01

UNLABELLED: Abstract Objectives: To determine the risk of recurrent anal sphincter rupture (ASR), and compare the risk of anal incontinence (AI) after recurrent ASR, with that seen in women with previous ASR who deliver by caesarean section or vaginally without sustaining a recurrent ASR. METHODS...

[Acute anal pain].

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Pittet, Olivier; Demartines, Nicolas; Hahnloser, Dieter

2013-07-01

Acute anal pain is a common proctological problem. A detailed history together with the clinical examination are crucial for the diagnosis. An acute perianal vein thrombosis can be successfully excised within the first 72 hours. Acute anal fissures are best treated conservatively using stool regulation and topical medications reducing the sphincter spasm. A chronic anal fissure needs surgery. Perianal abscesses can very often be incised and drained in local anesthesia. Proctalgia fugax and the levator ani syndrome are exclusion diagnoses and are treated symptomatically.

Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

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Petrelli, Alessio; Di Napoli, Anteo; Giorgi Rossi, Paolo; Rossi, Alessandra; Luccini, Daniele; Di Marco, Ilaria; Traoré, Amadou Laico; Gillio Tos, Anna; Trevisan, Morena; Mirisola, Concetta; Costanzo, Gianfranco

2016-10-01

In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+ using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US in Catalonia, Spain

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Ibáñez Raquel

2012-01-01

Full Text Available Abstract Background A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US. HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+ in women with a cytological diagnosis of ASC-US. Methods During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Results Among the 611 women diagnosed with ASC-US, 493 (80.7% had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years. hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions -HSIL were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI = 85.5-99.9 and specificity was 68.3% (95%CI

Discrepancies between biopsy-based and excision-based grading of cervical intraepithelial neoplasia: the important role of time between excision and biopsy.

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Zhang, Lu; Li, Qiang; Zhao, Mingyu; Jia, Lin; Zhang, Youzhong

2015-05-01

We sought to evaluate the rate of cervical intraepithelial neoplasia (CIN) ≤ 1 in loop electrosurgical excision procedure (LEEP) specimens after the treatment of biopsy-proven CIN 2-3, and to identify factors that are associated with the rate of CIN ≤ 1, especially focusing on the time interval between biopsy and LEEP. The goal of this research is to reduce the overtreatment of women with CIN 2-3. This was a retrospective study performed on women undergoing LEEP for biopsy-proven CIN 2-3 in Qilu hospital in Shandong, China. Patients were separated according to LEEP pathology (CIN ≤ 1 vs. CIN 2-3), and compared using the χ2 test and Student t test. The main outcome measures were pathologic discrepancy (defined as CIN 2-3 at biopsy, but CIN ≤ 1 at excision). Of the 391 women with biopsy-proven CIN 2-3, 26.9% had LEEP specimens with CIN ≤ 1 histologies. The likelihood of a CIN ≤ 1 LEEP specimen increases for greater biopsy-LEEP intervals (odds ratio, 1.374; 95% confidence interval, 1.089-1.735; P = 0.008). Cases in younger women and biopsy-assessed CIN 2 cases were both more likely to have CIN 1 or negative LEEP specimens. The rate of spontaneous histologic regression (defined as CIN ≤ 1 at resection) was 26.9%. These low-grade lesions were more common in LEEP specimens from young women with CIN 2 at biopsy, and who underwent LEEP later after the initial biopsy.

High-resolution magnetic resonance imaging of the anal sphincter using a dedicated endoanal receiver coil

International Nuclear Information System (INIS)

DeSouza, N.M.; Williams, A.D.; Gilderdale, D.J.

1999-01-01

The use of a surface coil in MR imaging improves signal-to-noise ratio of adjacent tissues of interest. We therefore devised an endoanal receiver coil for imaging the anal sphincter. The probe is solid and re-usable: it comprises a saddle geometry receiver with integral tuning, matching and decoupling. It is placed in the anal canal and immobilised externally. Both in vitro and in vivo normal anatomy is identified. The mucosa is high signal intensity, the submucosa low signal intensity, the internal sphincter uniformly high signal intensity and the external sphincter low signal intensity on T1- and T2-weighted images. In females, the transverse perineal muscle bridges the inferior part of the external sphincter anteriorly. In perianal sepsis, collections and the site of the endoanal opening are identified. In early-onset fecal incontinence following obstetric trauma/surgery, focal sphincter defects are demonstrated; in late-onset fecal incontinence external sphincter atrophy is seen. In fecally incontinent patients with scleroderma, forward deviation of the anterior sphincter musculature with descent of rectal air and feces into the anal canal is noted. The extent of sphincter invasion is assessed in low rectal tumours. In children with congenital anorectal anomalies, abnormalities of the muscle components are defined using smaller-diameter coils. Such information is invaluable in the assessment and surgical planning of patients with a variety of anorectal pathologies. (orig.)

Serous Tubal Intraepithelial Carcinoma or Not? Metastases to Fallopian Tube Mucosa Can Masquerade as In Situ Lesions.

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Singh, Reena; Cho, Kathleen R

2017-10-01

- Nonuterine high-grade serous carcinomas (HGSCs) are believed to arise most often from precursors in the fallopian tube referred to as serous tubal intraepithelial carcinomas (STICs). A designation of tubal origin has been suggested for all cases of nonuterine HGSC if a STIC is identified. - To highlight that many different types of nongynecologic and gynecologic carcinomas, including HGSC, can metastasize to the tubal mucosa and mimic de novo STIC. - A mini-review of several recently published studies that collectively examine STIC-like lesions of the fallopian tube. - The fallopian tube mucosa can be a site of metastasis from carcinomas arising elsewhere, and pathologists should exercise caution in diagnosing STIC without first considering the possibility of metastasis. Routinely used immunohistochemical stains can often be used to determine if a STIC-like lesion is tubal or nongynecologic in origin. In the context of uterine and nonuterine HGSC, STIC may represent a metastasis rather than the site of origin, particularly when widespread disease is present.

Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.

Directory of Open Access Journals (Sweden)

Hanna Johansson

Full Text Available Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic in predicting future development of high-grade cervical intraepithelial neoplasia (CIN among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS or low-grade squamous epithelial lesion (LSIL cytology.Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211 or LSIL, (n = 131 were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.Twenty-nine percent (61/211 of the women in the ASCUS group, and 34.3% (45/131 in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0 among women with ASCUS and 95.4% (95% CI 91.8-99.0 among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02. The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively. The corresponding specificity was low, 12.7% (95% CI 7.9-19.3 and 5.8% (95% CI 2.2-13.6, for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27 as compared to 13.6% (43/315 of the mRNA-positive women (p = 0.03.The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future

Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

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Johansson, Hanna; Bjelkenkrantz, Kaj; Darlin, Lotten; Dilllner, Joakim; Forslund, Ola

2015-01-01

Objective Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology. Methods Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+. Results Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03). Conclusion The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had

Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate

International Nuclear Information System (INIS)

Rodríguez-Berriguete, Gonzalo; Paniagua, Ricardo; Royuela, Mar; Fraile, Benito; Bethencourt, Fermín R de; Prieto-Folgado, Angela; Bartolome, Nahikari; Nuñez, Claudia; Prati, Bruna; Martínez-Onsurbe, Pilar; Olmedilla, Gabriel

2010-01-01

In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation. Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades). In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason). IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2)

Prevalence of Cervical Dysplasia among Women in Kano Municipal ...

African Journals Online (AJOL)

Fifty-seven women had cervical dysplasia giving a prevalence rate of 10.63%. Of the 57 women with cervical dysplasia, 21 (36.8%) had a low grade squamous intraepithelial lesions (LGSIL), while 36(63.2%) had a high grade squamous intraepithelial lesion (HGSIL). The disease was higher in grand multiparous clients ...

Neoplasia intraepitelial vulvar: um problema atual Vulvar intraepithelial neoplasia: a current problem

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José Alberto Fonseca-Moutinho

2008-08-01

Full Text Available A neoplasia intraepitelial da vulva (VIN é uma denominação que foi introduzida incialmente pela International Society for Study of Vulvo-vaginal Diseases (ISSVD e reconhecida posteriormente pela International Society of Gynaecological Pathology (ISGYP e Organização Mundial da Saúde. É uma entidade patológica a que correspondem as VIN de tipo usual (verrucoso, basalióide e misto e as VIN de tipo diferenciado. A incidência das lesões de VIN tem aumentado progressivamente, principalmente em mulheres jovens. A infecção pelo papilomavírus humano (HPV de alto risco, pelo vírus da imunodeficiência humana (HIV, o tabagismo e a neoplasia intraepitelial do colo do útero, da vagina e região anal são factores de risco estabelecidos para as VIN. Não existem sintomas e sinais característicos das VIN, mas a doença se traduz sempre por lesões clinicamente identificáveis. A biópsia com o auxílio do colposcópio permite o diagnóstico. O tratamento da doença está sempre justificado pelo elevado risco de progressão para cancro invasivo. A excisão alargada das lesões ou a sua destruição com laser CO2 têm sido os métodos mais populares de tratamento. Independentemente do método terapêutico utilizado, as taxas de recidiva são elevadas, pelo que está aconselhada a vigilância apertada das doentes após tratamento. A terapêutica tópica com imiquimod se afigura promissora no tratamento das VIN. As vacinas profiláticas contra os tipos de HPV de alto risco prometem se tornar armas poderosas na prevenção primária da doença.Vulvar intraepithelial neoplasia (VIN is a pathological denomination coined by the International Society for Study of Vulvo-vaginal Diseases (ISSVD and adopted by the International Society of Gynaecological Pathology (ISGYP and by the World Health Organization. VIN is a heterogeneous pathological entity with a usual type (warty, basaloid and mixed and a differentiated type. The incidence of the disease is

[Surgical treatment of anal fistula].

Science.gov (United States)

Zeng, Xiandong; Zhang, Yong

2014-12-01

Anal fistula is a common disease. It is also quite difficult to be solved without recurrence or damage to the anal sphincter. Several techniques have been described for the management of anal fistula, but there is no final conclusion of their application in the treatment. This article summarizes the history of anal fistula management, the current techniques available, and describes new technologies. Internet online searches were performed from the CNKI and Wanfang databases to identify articles about anal fistula management including seton, fistulotomy, fistulectomy, LIFT operation, biomaterial treatment and new technology application. Every fistula surgery technique has its own place, so it is reasonable to give comprehensive individualized treatment to different patients, which may lead to reduced recurrence and avoidance of damage to the anal sphincter. New technologies provide promising alternatives to traditional methods of management. Surgeons still need to focus on the invention and improvement of the minimally invasive techniques. Besides, a new therapeutic idea is worth to explore that the focus of surgical treatment should be transferred to prevention of the formation of anal fistula after perianal abscess.

Prevalência de lesões intraepiteliais em atipias de significado indeterminado em um serviço público de referência para neoplasias cervicais Prevalencia de lesiones intraepiteliales en atipias de significado indeterminado en un servicio público de referencia para neoplasias cervicales Prevalence of atypical squamous cell intraepithelial lesions of undetermined significance in a public health referral service for cervical cancer

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Railda Fraga Costa

2011-01-01

óstico colpocitológico de atipias de significado indeterminado (ASCUS fue del 23,7%, el aumento del riesgo fue directamente proporcional al de la edad y hubo mayor prevalencia de lesión intraepitelial de bajo grado, asociada a la infección por el Papilomavirus humano.OBJECTIVE: To determine the prevalence of low and high grade intraepithelial lesions in women with Pap smear diagnosis of atypical squamous cells of undetermined significance, in the city of Maceió, Alagoas. Knowing the influence of age and the etiological agents for sexually transmitted diseases on the risk of developing low and high grade intraepithelial lesions. METHODS: Cross sectional prevalence study at a public referral center for cervical cancer. We studied records of 253 women with atypical diagnoses of undetermined significance, in 2007. RESULTS: The prevalence of intraepithelial lesions was 23.7%; 26.7% were low grade and 73.3% high grade. CONCLUSIONS: The prevalence of high-grade intraepithelial lesions in women with Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS was 23.7%; the increase in risk was directly proportional to the age and higher prevalence of low grade squamous intraepithelial lesion associated with papillomavirus infection.

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

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Panagiotis Bountris

2014-01-01

Full Text Available 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.

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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.

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

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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.

Anal and penile high-risk human papillomavirus prevalence in HIV-negative and HIV-infected MSM

NARCIS (Netherlands)

van Aar, Fleur; Mooij, Sofie H.; van der Sande, Marianne A. B.; Speksnijder, Arjen G. C. L.; Stolte, Ineke G.; Meijer, Chris J. L. M.; Verhagen, Dominique W. M.; King, Audrey J.; de Vries, Henry J. C.; Schim van der Loeff, Maarten F.

2013-01-01

Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in MSM. Analysis of baseline data from a prospective cohort study. MSM aged 18 years or older were

High-resolution magnetic resonance imaging of the anal sphincter using a dedicated endoanal receiver coil

Energy Technology Data Exchange (ETDEWEB)

DeSouza, N.M.; Williams, A.D.; Gilderdale, D.J. [Dept. of Radiology, Imperial College School of Medicine, London (United Kingdom)

1999-04-01

The use of a surface coil in MR imaging improves signal-to-noise ratio of adjacent tissues of interest. We therefore devised an endoanal receiver coil for imaging the anal sphincter. The probe is solid and re-usable: it comprises a saddle geometry receiver with integral tuning, matching and decoupling. It is placed in the anal canal and immobilised externally. Both in vitro and in vivo normal anatomy is identified. The mucosa is high signal intensity, the submucosa low signal intensity, the internal sphincter uniformly high signal intensity and the external sphincter low signal intensity on T1- and T2-weighted images. In females, the transverse perineal muscle bridges the inferior part of the external sphincter anteriorly. In perianal sepsis, collections and the site of the endoanal opening are identified. In early-onset fecal incontinence following obstetric trauma/surgery, focal sphincter defects are demonstrated; in late-onset fecal incontinence external sphincter atrophy is seen. In fecally incontinent patients with scleroderma, forward deviation of the anterior sphincter musculature with descent of rectal air and feces into the anal canal is noted. The extent of sphincter invasion is assessed in low rectal tumours. In children with congenital anorectal anomalies, abnormalities of the muscle components are defined using smaller-diameter coils. Such information is invaluable in the assessment and surgical planning of patients with a variety of anorectal pathologies. (orig.) With 15 figs., 26 refs.

Identification of episomal human papillomavirus and other DNA viruses in cytological anal samples of HIV-uninfected men who have sex with men.

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Maria Gabriella Donà

Full Text Available To date, there have been only few studies that investigated integration of anal Human Papillomavirus (HPV. Most of them were conducted on HIV-infected individuals and mainly analyzed samples from high-grade lesions and invasive cancer. We aimed to investigate HPV physical status in HIV-negative men who have sex with men (MSM with a detectable anal HPV infection, irrespective of the presence of lesions. We also sought to explore the presence of other circular DNA viruses in the anal region. Study participants were attendees of an STI screening program, which were also screened for anal HPV infection and cytological abnormalities. HPV physical status was assessed using multiply-primed RCA. HPV16-positive samples were also analyzed using E2/E6 multiplex PCR, qRT-PCR and APOT assay. RCA and virus-specific PCR were employed to investigate the presence of other DNA viruses. Anal HPV infection was detected in 76.9% of the 230 MSM enrolled. The anal cytological reports were: 129 NILM, 37 ASC-US and 28 L-SIL (36 samples were inadequate for interpretation. HPV physical status was evaluated in the 109 anal specimens that harbored one or two different HPV genotypes. Integration was observed only in one HPV16-positive sample (0.9%, in which integrate-derived viral transcripts of type B were detected. Integration occurred in chromosome 14 q. In 22 of the 53 (41.5% mucosal HPV-negative samples, RCA restriction results would seem to indicate the presence of circular DNA viruses. Indeed, cutaneous HPV (4 samples, MCPyV (5 samples and TTV (4 samples were detected. In conclusion, anal HPV integration was rarely evidenced in HIV-uninfected MSM with no or mild anal cytological abnormalities, although the integration rate may have been underestimated because of the limitations of the employed assays. Other DNA viruses were detected in the anal samples of these individuals, although the significance of this occurrence needs to be assessed.

Treatment results in anal cancer: non-operative treatment versus operative treatment

Energy Technology Data Exchange (ETDEWEB)

Chie, Eui Kyu; Park, Jae Gahb; Bang, Yung Jue; Heo, Dae Seog; Kim, Noe Kyeong [Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung Whan [Medical Reasearch Center, Seoul National University, Seoul (Korea, Republic of)

2002-03-15

This study was undertaken to analyze the efficacy and sphincter preservation rate of platinum based neoadjuvant chemotherapy plus radiotherapy versus abdominoperineal resection and postoperative radiotherapy for anal cancer. Data of forty-two patients with anal cancer were retrospectively analyzed. Among thirty-eight patients with epidermoid histology, four patients received radiotherapy, and nineteen patients received abdominoperineal resection and adjuvant radiotherapy with or without chemotherapy (APR + RT {+-} CT), and fifteen patients received neoadjuvant chemotherapy and radiotherapy (CRT). The CRT regimen was composed of three cycles of 5-fluorouracil (1,000 mg/m{sup 2} bolus on D1 {approx} 5) and cisplatin (60 mg/m{sup 2} bolus on D1) followed by 50.4 Gy to the tumor bed and regional lymphatics over 5.5 weeks. Both inguinal lymphatics were treated with an identical dose schedule. Residual disease was treated with an additional three cycles of identical adjuvant chemotherapy. An identical dose schedule was used for post-operative radiotherapy. Median follow-up period was eighty-five months. Overall five-year survival rates were 80.3%, 88.9% and 79.4% for entire patients, APR + RT {+-} CT group, and the CRT group, respectively. No significant difference was found between the two groups ({rho} = 0.49). Anus preservation rate for the CRT group was 86.7%. Age ({rho} = 0.0164) and performance status ({rho} = 0.0007) were found to be significant prognostic factors by univariate analysis. Age ({rho} = 0.0426), performance status ({rho} = 0.0068), and inguinal lymph node metastasis ({rho} = 0.0093) were statistically significant prognostic factors by multivariate analysis. No case of RTOG grade 3 complication or higher was reported. This and other recent studies have shown that combined chemotherapy plus radiotherapy for anal cancer results in a high rate of anal sphincter preservation as well as local control and survival. Furthermore, neoadjuvant use of

Risk Factors for Cervical Intraepithelial Neoplasia

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Estrella de la Caridad Armenteros Espino

2016-09-01

Full Text Available Background: cervix cancer constitutes the second cause of death worldwide, with new diagnosis each year. Objective: to determine the risk factors of cervical intraepithelial neoplasia in the municipality of Cruces. Methods: it was developed an analytical research with case and control design from November 2013 to November 2014. The group of cases was formed of the 34 women with this diagnosis. There were selected 64 females from the same environment with the same age for the control group. The data obtained by surveys and clinical records reviews were presented in absolute numbers and percentages. It was used Chi-squared test and odd ratio. Results: 52 % of women with neoplasia were less than 25 years old. Significant differences were found which associate neoplasia with early sexual intercourse, sexually transmitted infections by Papilloma virus, Plane genital condyloma, and the use of oral contraceptive pills. Multiple sex partner was a frequent antecedent. Conclusion: risk factors associated to cervical intraepithelial neoplasia in the group of women studied in the Cruces municipality were early sexual intercourse, mainly before 15 years old, multiple sex partner, sexually communicated diseases and the use of oral contraceptive pills for more than 5 years.

Initial prevalence of anal human papilloma virus infection in liver transplant recipients.

Science.gov (United States)

Grąt, Michał; Grąt, Karolina; Hołówko, Wacław; Malejczyk, Magdalena; Walter de Walthoffen, Szymon; Lewandowski, Zbigniew; Kobryń, Konrad; Patkowski, Waldemar; Majewski, Sławomir; Młynarczyk, Grażyna; Krawczyk, Marek

2014-08-01

Although liver transplant recipients are at increased risk of human papilloma virus (HPV)-related anal cancer, limited data are available regarding the initial prevalence of anal HPV infection in this population. Anal swabs collected from 50 liver transplant recipients within the first three postoperative weeks were subjected to real-time polymerase chain reaction for detection of the four HPV genotypes: 6, 11, 16, and 18. Predictors of any, low-risk, and high-risk anal HPV infection were evaluated. Overall, the prevalence of any anal HPV infection was 18.0%, with the corresponding rates for high- and low-risk HPV genotypes being 8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in patients with hepatitis B virus (HBV) infection (P = 0.027), ≥3 sexual partners (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only factor significantly associated with high-risk HPV infection (P = 0.038). Male sex (P = 0.050), age ≥52 years (P = 0.016), ≥30 sexual partners (P = 0.003), age at first intercourse ≤18 years (P = 0.045), and time since first intercourse ≥38 years (P = 0.012) were identified as predictors of low-risk HPV infection. These results indicate that HPV vaccination of liver transplant candidates and screening for anal HPV infection in high-risk groups should be considered. © 2014 Steunstichting ESOT.

High Prevalence and Genotype Diversity of Anal HPV Infection among MSM in Northern Thailand.

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Taweewat Supindham

Full Text Available HPV infection is common and may cause cancer among men who have sex with men (MSM. Anal HPV infection (HPV+ was found in 85% of HIV-positive (HIV+ and 59% of HIV-negative (HIV- MSM in Bangkok, central Thailand. As little is known about HPV in this group in northern Thailand, we studied MSM subgroups comprised of gay men (GM, bisexual men (BM, and transgender women (TGW.From July 2012 through January 2013, 85 (42.5% of 200 GM, 30 (15% BM, and 85 (42.5% TGW who practiced receptive anal intercourse were recruited after informed consent, followed by self-assisted computer interview, HIV testing, and anal swabs for HPV genotyping.Of 197 adequate specimens, the overall prevalence of any HPV was 157 (80%. Prevalence was 89% (76/85 in GM, 48% (14/29 in BM, and 81% (67/83 in TGW. The most common high-risk types were HPV16 (27% of 197, HPV58 (23%, and HPV51 (18%. Prevalence of high-risk types was 74% in 85 GM, 35% in 29 BM, and 71% in 83 TGW. Prevalence of any HPV type, or high-risk type, was 100% and 94%, respectively, among 48 HIV+ MSM, 70% and 54% among 120 HIV- MSM. Of the 197 specimens, 36% (70 had HPV types 16 and/or 18 in the bivalent vaccine, compared to 48% (95 with ≥1 of types 16/18/06/11 in the quadrivalent, 56% (111 for 16/18/31/33/45/52/58 in the 7-valent, and 64% (126 for 16/18/31/33/45/52/58/06/11 in the 9-valent. HIV+, GM, and TGW were independently associated with HPV infection.We found higher rates of both any HPV and high-risk types than previous studies. Among the heretofore unstudied TGW, their equivalent HPV rates were comparable to GM. Current and investigational HPV vaccines could substantially protect GM, BM, and TGW from the serious consequences of HPV infection especially among HIV + MSM.

Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model

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Uddhav P. Kelavkar

2006-06-01

Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study.

Science.gov (United States)

Tai, Yi Jou; Chen, Yun Yuan; Hsu, Huang Cheng; Chiang, Chun Ju; You, San Lin; Chen, Chi An; Cheng, Wen Fang

2018-07-01

To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Cognitive impairments in patients with low grade gliomas and high grade gliomas

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Eliane C. Miotto

2011-08-01

Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

An electron microscopic study of intraepithelial nerves of oral mucosa of rats during aging

International Nuclear Information System (INIS)

Choi, Dai Ho; You, Dong Soo

1984-01-01

Observation made in this study bring home salient features that may contribute towards a better understanding of the relationship between the available physiologic data and anatomical characteristics of those nerve fibers that penetrate into the intraepithelial space in the oral cavity. The present investigation characterized the fine structure of nerve fibers in oral mucosae with respect to the manner in which presumed sensory fibers enter into the intraepithelial space by penetration of the basal lamina. The conclusions were made little discernible qualitative difference exists between young and old animals, concerning the fine structural characteristics of nerve fibers and nerve endings and in old animals, significant reductions exist in the number of neural elements in the intraepithelial space.

Evaluation of a low-cost liquid-based Pap test in rural El Salvador: a split-sample study.

Science.gov (United States)

Guo, Jin; Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Felix, Juan C

2014-04-01

We sought to test the diagnostic efficacy of a low-cost, liquid-based cervical cytology that could be implemented in low-resource settings. A prospective, split-sample Pap study was performed in 595 women attending a cervical cancer screening clinic in rural El Salvador. Collected cervical samples were used to make a conventional Pap (cell sample directly to glass slide), whereas residual material was used to make the liquid-based sample using the ClearPrep method. Selected samples were tested from the residual sample of the liquid-based collection for the presence of high-risk Human papillomaviruses. Of 595 patients, 570 were interpreted with the same diagnosis between the 2 methods (95.8% agreement). There were comparable numbers of unsatisfactory cases; however, ClearPrep significantly increased detection of low-grade squamous intraepithelial lesions and decreased the diagnoses of atypical squamous cells of undetermined significance. ClearPrep identified an equivalent number of high-grade squamous intraepithelial lesion cases as the conventional Pap. High-risk human papillomavirus was identified in all cases of high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and cancer as well as in 78% of low-grade squamous intraepithelial lesions out of the residual fluid of the ClearPrep vials. The low-cost ClearPrep Pap test demonstrated equivalent detection of squamous intraepithelial lesions when compared with the conventional Pap smear and demonstrated the potential for ancillary molecular testing. The test seems a viable option for implementation in low-resource settings.

What drives the number of high-risk human papillomavirus types in the anal canal in HIV-positive men who have sex with men?

NARCIS (Netherlands)

del Amo, Julia; González, Cristina; Geskus, Ronald B.; Torres, Montse; del Romero, Jorge; Viciana, Pompeyo; Masiá, Mar; Blanco, Jose R.; Hernández-Novoa, Beatriz; Ortiz, Marta; Peña, Alejandro; García, Federico; Torres, Montserrat; Ocampo, Antonio; Da Silva, Alfredo Rodríguez; Miralles, Celia; Mauricio Iribarren, Gustavo; Madrid, Nadia; Dronda, Fernando; Benito, Amparo; Sanz, Itziar; Vera, Mar; Rodríguez, Carmen; Martín Alegre, Carmen; Carlos Carrió, Juan; Raposo, Montse; Trastoy, Mónica; Fontillón, Maria; Robledano, Catalina; Gutierrez, Félix; Padilla, Sergio; Andrada, Encarna; Cervero, Miguel; Ramón Blanco, José; Pérez, Laura; Portilla, Joaquín; Portilla, Irene; Angel Vonwichmann, Miguel; Antonio Iribarren, José; Camino, Xabier; Sendagorta, Elena; Herranz, Pedro; Rodríguez, Patricia; Luis Gómez, Juan; Rosado, Dacil; Alejos, Belén; Angeles Rodríguez, Maria

2013-01-01

We estimated the effect of sexual behavior, age, and immunodeficiency on the number of high-risk human papillomavirus (HR-HPV) types in the anal canal among human immunodeficiency virus-positive men who have sex with men (MSM). Anal samples were genotyped with the Linear Array HPV Genotyping Test,

Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

Science.gov (United States)

Yang, Jack; Nolte, Fredrick S; Chajewski, Olga S; Lindsey, Kathryn G; Houser, Patricia M; Pellicier, Jalidsa; Wang, Qun; Ehsani, Laleh

2018-01-01

Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities. © 2017 Wiley Periodicals, Inc.

Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

Science.gov (United States)

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.

Anal Sphincter Augmentation Using Biological Material.

Science.gov (United States)

Alam, Nasra N; Narang, Sunil K; Köckerling, Ferdinand; Daniels, Ian R; Smart, Neil J

2015-01-01

The aim of this review is to provide an overview of the use of biological materials in the augmentation of the anal sphincter either as part of an overlapping sphincter repair (OSR) or anal bulking procedure. A systematic search of PubMed was conducted using the search terms "anal bulking agents," "anal sphincter repair," or "overlapping sphincter repair." Five studies using biological material as part of an overlapping sphincter repair (OSR) or as an anal bulking agent were identified. 122 patients underwent anal bulking with a biological material. Anorectal physiology was conducted in 27 patients and demonstrated deterioration in maximum resting pressure, and no significant change in maximum squeeze increment. Quality of life scores (QoLs) demonstrated improvements at 6 weeks and 6 months, but this had deteriorated at 12 months of follow up. Biological material was used in 23 patients to carry out an anal encirclement procedure. Improvements in QoLs were observed in patients undergoing OSR as well as anal encirclement using biological material. Incontinence episodes decreased to an average of one per week from 8 to 10 preoperatively. Sphincter encirclement with biological material has demonstrated improvements in continence and QoLs in the short term compared to traditional repair alone. Long-term studies are necessary to determine if this effect is sustained. As an anal bulking agent the benefits are short-term.

Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development.

Science.gov (United States)

Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W

2016-06-01

Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.

Prevalence and severity of cervical squamous intraepithelial lesion ...

African Journals Online (AJOL)

Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming reports associating SIL and HIV infection, however in Tanzania such reports are limited. A cross-sectional hospital-based descriptive study was ...

[Caesarean section and anal incontinence].

Science.gov (United States)

Kalis, V; Stipán, J; Chaloupka, P; Karbanová, J; Rokyta, Z

2008-04-01

Summary of the impact of Caesarean section on anal incontinence. Review. Department of Gynaecology and Obstetrics, Charles University and University Hospital Plzen. Review of the current international literature. Currently, Caesarean section is not considered to reduce symptoms of anal incontinence. If there is any reduction of symptoms, that remains only for a short term (40% in 3 months after the delivery in the largest trial). In a long term, virtually in no trial has been observed any difference, and others, non-obstetrical factors (particularly aging) prevail. Current knowledge does not allow to assess sufficiently pros and cons of Caesarean compared to vaginal delivery. High risk groups, that would profit from elective Ceasarean, have not been clearly identified yet.

Complex anal fistulas: plug or flap?

Science.gov (United States)

Muhlmann, Mark D; Hayes, Julian L; Merrie, Arend E H; Parry, Bryan R; Bissett, Ian P

2011-10-01

Rectal mucosal advancement flaps (RMAF) and fistula plugs (FP) are techniques used to manage complex anal fistulas. The purpose of this study was to review and compare the results of these methods of repair. A retrospective review of all complex anal fistulas treated by either a RMAF or a FP at Auckland City Hospital from 2004 to 2008. Comparisons were made in terms of successful healing rates, time to failure and the use of magnetic resonance imaging. Overall, 70 operations were performed on 55 patients (55.7% male). The mean age was 44.9 years. Twenty-one patients (30%) had had at least one previous unsuccessful repair. Indications for repair included 57 high cryptoglandular anal (81%), 4 Crohn's anal (6%), 7 rectovaginal (10%), 1 rectourethral (1%) and 1 pouch-vaginal fistula (1%). All patients were followed up with a mean of 4.5 months. Forty-eight RMAFs (69% of total) were performed with 16 successful repairs (33%). Twenty-two FPs (31% of total) were performed with 7 successful repairs (32%, P = 0.9). In failed repairs, there was no difference in terms of mean time to failure (RMAF 4.8 months versus FP 4.1 months, P = 0.62). Magnetic resonance imaging was performed in 21 patients (37%) before the repair. The success rate in these patients was 20%. The results of treatment of complex anal fistulas are disappointing. The choice of operation of either a RMAF or a FP did not alter the poor healing rates of about one third of patients in each group.

Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests

DEFF Research Database (Denmark)

Rebolj, Matejka; Bonde, Jesper; Njor, Sisse Helle

2011-01-01

To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard = 1 relative light units/cut-off level (rlu/co).......To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard = 1 relative light units/cut-off level (rlu/co)....

Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

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Chang Hun Lee

Full Text Available Little is known about the epidemiology on human papillomavirus (HPV infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea.A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour.A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM and 68 from men who have sex with women (MSW. Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001. High-risk HPV (HR-HPV prevalence was higher among MSM (47.4% than MSW (25.0%; P = 0.002. The HR-HPV types identified most frequently were HPV 16 (11%, HPV 18 (9.9%, and HPV 58 (5% in MSM, and HPV 58(11% and HPV 16 (8.9% in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001. Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001. In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection.Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

The 2001 Bethesda System

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Bergeron Christine

2003-01-01

Full Text Available The Bethesda system is a system of terminology for reporting the results of cervical cytology. It was developed in 1988, and is now widely used in the United States. This system was updated in April 2001. The most important modifications are the following: a elimination of the category "satisfactory but limited by", b the reintegration of benign modifications in the normal category, c "atypical squamous cells of undetermined significance" is now named "atypical squamous cells" and subdivided into "atypical squamous cells of undetermined significance" and "cannot exclude high grade squamous intraepithelial lesion"; and d endocervical adenocarcinoma in situ which is now a separate entity. Low grade squamous intraepithelial lesions and high grade squamous intraepithelial cells remain unchanged. Recommendations have been proposed concerning automated review and ancillary testing.

Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

Science.gov (United States)

d'Assuncao, Jefferson; Irwig, Les; Macaskill, Petra; Chan, Siew F; Richards, Adele; Farnsworth, Annabelle

2007-01-01

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology. Design Prospective study. Setting Pathology laboratory in Sydney, Australia. Participants 55 164 split sample pairs (liquid based sample collected after conventional sample from one collection) from consecutive samples of women choosing both types of cytology and whose specimens were examined between August 2004 and June 2005. Main outcome measures Primary outcome was accuracy of slides for detecting squamous lesions. Secondary outcomes were rate of unsatisfactory slides, distribution of squamous cytological classifications, and accuracy of detecting glandular lesions. Results Fewer unsatisfactory slides were found for imager read cytology than for conventional cytology (1.8% v 3.1%; Pcytology (7.4% v 6.0% overall and 2.8% v 2.2% for cervical intraepithelial neoplasia of grade 1 or higher). Among 550 patients in whom imager read cytology was cervical intraepithelial neoplasia grade 1 or higher and conventional cytology was less severe than grade 1, 133 of 380 biopsy samples taken were high grade histology. Among 294 patients in whom imager read cytology was less severe than cervical intraepithelial neoplasia grade 1 and conventional cytology was grade 1 or higher, 62 of 210 biopsy samples taken were high grade histology. Imager read cytology therefore detected 71 more cases of high grade histology than did conventional cytology, resulting from 170 more biopsies. Similar results were found when one pathologist reread the slides, masked to cytology results. Conclusion The ThinPrep Imager detects 1.29 more cases of histological high grade squamous disease per 1000 women screened than conventional cytology, with cervical intraepithelial neoplasia grade 1 as the threshold for referral to colposcopy. More imager read slides than conventional slides were satisfactory for examination and more contained low grade cytological

Cervical squamous and glandular intraepithelial neoplasia: identification and current management approaches Neoplasia intraepitelial cervical escamosa y glandular: identificación y estrategias de manejo

Directory of Open Access Journals (Sweden)

V Cecil Wright

2003-01-01

Full Text Available Certain types of human papillomaviruses (HPV are associated with squamous intraepithelial lesions and cancer and these are termed high-risk. HPV type 16 is detected in approximately half of the high-grade squamous intraepithelial lesions and cancer. Because of the high rate of spontaneous regression of low-grade squamous lesions, follow-up by cytology, colposcopy and possible biopsy appears preferable. Due to the higher rate of progression to malignancy of the high-grade lesions conservative treatment is recommended. One of the most common reasons for persistence relates to the human immunodeficiency virus. Adenocarcinoma in situ is an uncommon disorder and not well identified by cytologic sampling or colposcopic inspection. The diagnosis is made by cone biopsy, the specimen having negative margins for disease. Hysterectomy is the treatment procedure of choice unless fertility is an issue. Excisional methods (particularly electrosurgical loop can interfere with accurate histological interpretation in some cases of both squamous disease and adenocarcinoma in situ.Ciertos tipos de virus del papiloma humano (VPH, denominados de alto riesgo, están asociados con lesiones escamosas intraepiteliales y cáncer invasor. El VPH tipo 16 es detectado en aproximadamente la mitad de las lesiones escamosas intraepiteliales de alto grado y cáncer. Sin embargo, existe una elevada proporción de regresión espontánea en lesiones escamosas de bajo grado, por lo que para su monitoreo es preferible la utilización de citología, colposcopía y biopsia. Asimismo, debido a la elevada tasa de progresión a malignidad de lesiones de alto grado se recomienda un tratamiento conservador. Una de las razones comunes relacionadas con la persistencia de infección por el VPH es el virus de inmunodeficiencia humana. Por otra parte, el adenocarcinoma in situ es un trastorno raro, no bien identificado en muestras citológicas o de inspección colposcópica; el diagnóstico se

HIV/AIDS, HPV and Anal Cancer

Science.gov (United States)

Wang, Chia-ching J.; Sparano, Joseph; Palefsky, Joel M.

2016-01-01

SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index. PMID:27889034

High bone sialoprotein (BSP expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

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Tao Xu

Full Text Available OBJECTIVES: To investigate the expression and prognostic value of bone sialoprotein (BSP in glioma patients. METHODS: We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001. Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS and overall survival (OS in both grade III and grade IV glioma patients [hazard ratio (HR = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6-methylguanine (O(6-meG DNA methyltransferase (MGMT methylation and Karnofsky performance score (KPS less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

Pap smears for men: a vision of the future?

LENUS (Irish Health Repository)

Oon, S F

2012-02-01

BACKGROUND: Anal intraepithelial neoplasia (AIN) rarely receives as much publicity as its neighbouring orifice, the cervix. As in the cervix, intraepithelial neoplasias are precursors to cancer in the anal canal. AIN and cervical interstitial neoplasia (CIN) undergo dysplasia as a consequence of human papillomavirus (HPV) infection. Since the advent of screening with the Pap smear in CIN, cervical cancer has plummeted to a fifth of its initial incidence. Anal cancer, however, has been rising, with a predilection for human immunodeficiency virus-infected men. HPV causes a squamous epithelial dysplasia and converts healthy tissue into AINs of increasing severity until anal cancer manifests. CLINICAL CASE: This article describes a clinical case of anogenital HPV infection refractory to medical and surgical therapy. It also describes an effective surgical excision technique associated with a good cosmetic outcome. CONCLUSIONS: The paper concludes by briefly discussing the implications of a national screening programme against AIN in the future.

Interobserver reproducibility of the histological diagnosis of cervical dysplasia, Hospital San Juan de Dios, from January to December 2010

International Nuclear Information System (INIS)

Morales Navarro, Karla Andrea

2013-01-01

The reproducibility of the histological diagnosis of cervix specimens processed by the Pathology Service of the San Juan de Dios Hospital from January to December 2010 was determined. When operational failures were detected, possible improvement processes were proposed, guided by the study's findings. A moderate concordance for the Bethesda System and poor to moderate for the classification of Cervical Intraepithelial Neoplasia, was obtained after analyzing the diagnoses issued by the observers when comparing the pairs of pathologists. The concordance was moderate when comparing each pathologist with the standard for both classifications. The correlation was excellent when comparing the Classification Cervical Intraepithelial Neoplasia versus the Bethesda System. The categories with highest concordance were high-grade intraepithelial lesion and cervical intraepithelial neoplasia 3 and minor agreement were low-grade intraepithelial lesion and cervical intraepithelial neoplasia 2. The results agree and in some cases the results exceed the reproduction noted in the literature world medical [es

Characteristic findings of cervical Papanicolaou tests from transgender patients on androgen therapy: Challenges in detecting dysplasia.

Science.gov (United States)

Adkins, B D; Barlow, A B; Jack, A; Schultenover, S J; Desouki, M M; Coogan, A C; Weiss, V L

2018-02-28

The characteristic features of Papanicolaou (Pap) tests collected from female-to-male (FTM) transgender patients on androgen therapy have not been well defined in the literature. FTM transgender patients require cervical cancer screening with the same recommended frequency as cis-gender females. Dysplasia remains challenging to differentiate from atrophy. Without pertinent history, the atrophic findings in younger transgender patients can be misinterpreted as high-grade dysplasia. A review of all cervical Pap tests of transgender patients receiving androgen therapy (2010-2017) was performed. Bethesda diagnosis, cytomorphological features, HPV testing and cervical biopsy results were reviewed. Eleven transgender patients receiving androgen therapy were identified with 23 cervical Pap tests, 11 HPV tests and five cervical biopsies performed. A review of the Pap tests demonstrated: 57% negative for intraepithelial lesion; 13% unsatisfactory; 13% atypical squamous cells of undetermined significance; 13% atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion; and 4% high-grade squamous intraepithelial lesion. The rates of abnormal tests were higher than our age-matched cis-gender atrophic cohort rates of unsatisfactory (0.5%), atypical squamous cells of undetermined significance (7%), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (0%) and high-grade squamous intraepithelial lesion (0.5%). The cytological findings from liquid-based preparations included dispersed and clustered parabasal-type cells, scattered degenerated cells, smooth evenly dispersed chromatin, and occasional mild nuclear enlargement and irregularity. Dysplastic cells had larger nuclei, hyperchromatic clumped chromatin, and more irregular nuclear contours. The evaluation of dysplasia can be challenging on Pap tests from transgender patients on androgen therapy. The cohort evaluated had higher rates of unsatisfactory and abnormal Pap tests

TMEM45A, SERPINB5 and p16INK4A transcript levels are predictive for development of high-grade cervical lesions

DEFF Research Database (Denmark)

Manawapat-Klopfer, Anna; Thomsen, Louise T; Martus, Peter

2016-01-01

Women persistently infected with human papillomavirus (HPV) type 16 are at high risk for development of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+). We aimed to identify biomarkers for progression to CIN3+ in women with persistent HPV16 infection. In this prospective study......, 11,088 women aged 20-29 years were enrolled during 1991-1993, and re-invited for a second visit two years later. Cervical cytology samples obtained at both visits were tested for HPV DNA by Hybrid Capture 2 (HC2), and HC2-positive samples were genotyped by INNO-LiPA. The cohort was followed for up...... to 19 years via a national pathology register. To identify markers for progression to CIN3+, we performed microarray analysis on RNA extracted from cervical swabs of 30 women with persistent HPV16-infection and 11 HPV-negative women. Six genes were selected and validated by quantitative PCR. Three genes...

Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions

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G Kir

2012-01-01

Conclusion: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed.

ANAL SPHINCTER INJURIES (OASIS AT DELIVERY

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Katja Jakopič

2018-02-01

Full Text Available Background: Anal incontinence severely impairs quality of life. It affects 4 to 19 % of women and is statistically related to number of vaginal deliveries. It is grossly underreported and most patients that do seek help are referred to gastroenterologists or colorectal surgeons. Incidence of recognized sphincter injuries at time of delivery is 1 to 2 %. However studies with anal ultrasound showed incidence of anal sphincter injuries at 28 to 41 %. Depending on the degree of injury symptoms range from partial to complete inability to control passing of winds, liquid or solid stools. About three thirds of patients are asymp- tomatic in puerperium, however half of them are at risk of developing anal incontinence in later life. Hypoestrogenisem, additional perineal trauma during consequent deliveries and sphincter atrophy can unmask anal sphincter damage years later. Timely recognition and treatment are vital for good long term results and quality of life, if possible immediately after delivery. Good knowledge of perineal anatomy, recognition of risk factors, intense search and appropriate treatment and follow-up are essential to management of anal sphincter injuries. All secondary sphincter repair is less effective. Content: Updated overview of current opinion and guidelines on anal sphincter injuries are pre- sented. Anal sphincter is composed of external anal sphincter (EAS and internal anal sphincter (IAS. Striated EAS is divided into three parts – subcutaneous, superficial, deep, and con- nected to puborectalis muscle posteriorly. Smooth-muscled IAS is a continuation of a cir- cular smooth-muscle layer of rectum. In between there is a thin longitudinal muscle layer. IAS constitutes 70 % of resting tone and is under constant contraction. EAS contributes to 30 % of resting tone and almost all pressure during active contraction. EAS injury leads to insufficient contraction after rectal sampling and filling which causes urgency – patient can

High-grade and low-grade gliomas: differentiation by using perfusion MR imaging

International Nuclear Information System (INIS)

Hakyemez, B.; Erdogan, C.; Ercan, I.; Ergin, N.; Uysal, S.; Atahan, S.

2005-01-01

AIM: Relative cerebral blood volume (rCBV) is a commonly used perfusion magnetic resonance imaging (MRI) technique for the evaluation of tumour grade. Relative cerebral blood flow (rCBF) has been less studied. The goal of our study was to determine the usefulness of these parameters in evaluating the histopathological grade of the cerebral gliomas. METHODS: This study involved 33 patients (22 high-grade and 11 low-grade glioma cases). MRI was performed for all tumours by using a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence followed by conventional MRI. The rCBV and rCBF were calculated by deconvolution of an arterial input function. The rCBV and rCBF ratios of the lesions were obtained by dividing the values obtained from the normal white matter of the contralateral hemisphere. For statistical analysis Mann-Whitney testing was carried out. A p value of less than 0.05 indicated a statistically significant difference. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBV and rCBF ratios and grade of gliomas. Their cut-off value permitting discrimination was calculated. The correlation between rCBV and CBF ratios and glioma grade was assessed using Pearson correlation analysis. RESULTS: In high-grade gliomas, rCBV and rCBF ratios were measured as 6.50±4.29 and 3.32±1.87 (mean±SD), respectively. In low-grade gliomas, rCBV and rCBF ratios were 1.69±0.51 and 1.16±0.38, respectively. The rCBV and rCBF ratios for high-grade gliomas were statistically different from those of low-grade gliomas (p 0.05). The cut-off value was taken as 1.98 in the rCBV ratio and 1.25 in the rCBF ratio. There was a strong correlation between the rCBV and CBF ratios (Pearson correlation = 0.830, p<0.05). CONCLUSION: Perfusion MRI is useful in the preoperative assessment of the histopathologicalal grade of gliomas; the rCBF ratio in addition to the rCBV ratio can be incorporated

Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet

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Barbara Zanini

2016-08-01

Full Text Available The gluten-free diet (GFD is the only validated treatment for celiac disease (CD, but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control. Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta T cell and eosinophils significantly decreased at GCED control (Cohort A and at late control (Cohort B, compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696

French multicentre clinical evaluation of helical TomoTherapy® for anal cancer in a cohort of 64 consecutive patients

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Vendrely, V.; Henriques de Figueiredo, B.; Rio, E.; Benech, J.; Belhomme, S.; Lisbona, A.; Frison, E.; Doussau, A.; Nomikossoff, N.; Mahé, M. A.; Kantor, G.; Maire, J. P.

2015-01-01

.3 %), and hematologic (17.2 %) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed. TomoTherapy® for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement

Encopresis and anal masturbation.

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Aruffo, R N; Ibarra, S; Strupp, K R

2000-01-01

Current pediatric and psychiatric studies on encopresis and its treatment are heavily influenced by mechanical, physiological, and behavioral considerations. Although psychodynamic treatment has generally been considered to be of little benefit, and its findings suspect, the authors suggest that a psychodynamic approach adds substantially to the understanding of some cases of encopresis; that the anal sensations and anal erotic feelings reported by a number of encopretic children are intense, and that the encopretic symptom, soiling, in these children is the result of a conscious form of anal masturbation in which the fecal mass is used for stimulation; and that any study of encopresis is incomplete that does not include what encopretic children, engaged in a sound therapeutic relationship, know and say about their soiling. The authors further suggest that physical treatments of those children whose encopresis is psychologically driven may be contraindicated. The presence of a large stool does not in itself substantiate a physical illness. Further research is needed to elucidate the prevalence of anal masturbation in encopretic children.

Cold-knife and laser conization for cervical intraepithelial neoplasia

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Tabor, A; Berget, A

1990-01-01

In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III. Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive. In all other cases, local destruction was the operation of choice...

Analysis of DTI-Derived Tensor Metrics in Differential Diagnosis between Low-grade and High-grade Gliomas.

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Jiang, Liang; Xiao, Chao-Yong; Xu, Quan; Sun, Jun; Chen, Huiyou; Chen, Yu-Chen; Yin, Xindao

2017-01-01

Purpose: It is critical and difficult to accurately discriminate between high- and low-grade gliomas preoperatively. This study aimed to ascertain the role of several scalar measures in distinguishing high-grade from low-grade gliomas, especially the axial diffusivity (AD), radial diffusivity (RD), planar tensor (Cp), spherical tensor (Cs), and linear tensor (Cl) derived from diffusion tensor imaging (DTI). Materials and Methods: Fifty-three patients with pathologically confirmed brain gliomas (21 low-grade and 32 high-grade) were included. Contrast-enhanced T1-weighted images and DTI were performed in all patients. The AD, RD, Cp, Cs, and Cl values in the tumor zone, peritumoral edema zone, white matter (WM) adjacent to edema and contralateral normal-appearing white matter (NAWM) were calculated. The DTI parameters and tumor grades were statistically analyzed, and receiver operating characteristic (ROC) curve analysis was also performed. Results: The DTI metrics in the affected hemisphere showed significant differences from those in the NAWM, except for the AD values in the tumor zone and the RD values in WM adjacent to edema in the low-grade groups, as well as the Cp values in WM adjacent to edema in the high-grade groups. AD in the tumor zone as well as Cs and Cl in WM adjacent to edema revealed significant differences between the low- and high-grade gliomas. The areas under the curve (Az) of all three metrics were greater than 0.5 in distinguishing low-grade from high-grade gliomas by ROC curve analysis, and the best DTI metric was Cs in WM adjacent to edema (Az: 0.692). Conclusion: AD in the tumor zone as well as Cs and Cl in WM adjacent to edema will provide additional information to better classify gliomas and can be used as non-invasive reliable biomarkers in glioma grading.

Impact of hypothyroidism on primary anal malignant melanoma: A rare entity

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Siddharth Singh

2014-01-01

Full Text Available Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

Impact of hypothyroidism on primary anal malignant melanoma: a rare entity.

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Singh, Siddharth; Verma, Satyajeet; Kala, Sanjay

2014-01-01

Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

Internal anal sphincter: Clinical perspective.

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Kumar, Lalit; Emmanuel, Anton

2017-08-01

To summarise current knowledge of Internal anal sphincter. The internal anal sphincter (IAS) is the involuntary ring of smooth muscle in the anal canal and is the major contributor to the resting pressure in the anus. Structural injury or functional weakness of the muscle results in passive incontinence of faeces and flatus. With advent of new assessment and treatment modalities IAS has become an important topic for surgeons. This review was undertaken to summarise our current knowledge of internal anal sphincter and highlight the areas that need further research. The PubMed database was used to identify relevant studies relating to internal anal sphincter. The available evidence has been summarised and advantages and limitations highlighted for the different diagnostic and therapeutic techniques. Our understanding of the physiology and pharmacology of IAS has increased greatly in the last three decades. Additionally, there has been a rise in diagnostic and therapeutic techniques specifically targeting the IAS. Although these are promising, future research is required before these can be incorporated into the management algorithm. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Vaccine-preventable anal human papillomavirus in Australian gay and bisexual men

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I. Mary Poynten

2017-06-01

Full Text Available Objective: HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM. Methods: The Study of the Prevention of Anal Cancer (SPANC is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status. Results: Anal HPV results from 606 (98.2% of 617 participants (median age 49 years, 35.7% HIV-positive showed 525 (86.7% had ≥1 HPV type and 178 (29.4% had HPV16. Over one third of participants (214, 35.3% had no nonavalent vaccine-preventable types detected. Two (0.3% participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p<0.001 and younger participants (p=0.059 were more likely to have more vaccine-preventable HPV types detected. Conclusion: Anal HPV was highly prevalent in this largely community-based GBM cohort. Vaccine-preventable HPV16 was detected in approximately one third of participants. These findings suggest that the potential efficacy of HPV vaccination of older GBM should be explored. Keywords: Human papillomavirus, HPV, Anal, Vaccine, Prevalence, Gay and bisexual men, MSM, HIV

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

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Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Presence of high-grade intraepithelial lesions among women deprived of their liberty: a documental study Presencia de lesiones intraepiteliales de alto grado a las mujeres privadas de libertad: estudio documental Presença de lesões intraepiteliais de alto grau entre mulheres privadas de liberdade: estudo documental

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Paula Renata Amorim Lessa

2012-04-01

Full Text Available The aim of this study was to analyze the results of the Pap smears of women deprived of their liberty. It is a retrospective, documental study, with a quantitative approach, performed in a female prison of Ceará, Brazil, with a sample of 672 patient records. Regarding the microbiological findings, it was verified that the main cervical-vaginal colonization was by bacilli suggestive of Gardnerella/Mobiluncus (21.8%, followed by Trichomonas vaginalis (12%, and Candida sp (5.8%. The frequencies of samples with atypical cells presented rates of 4.1% for Atypical Cells of Undetermined Significance; 3.2% for Low-grade Intraepithelial Lesions; and 2.5% for High-grade Intraepithelial Lesions. The importance of screening for cervical cancer in female prisons was highlighted, as well as the inclusion of the nurse in this environment, ensuring individualized, quality care for women deprived of their liberty.El objetivo fue analizar los resultados de la prueba de Papanicolaou de mujeres privadas de libertad. Tipo de estudio documental, con un enfoque cuantitativo, desarrollado en una cárcel de mujeres en Ceará-Brasil, con muestra de 672 archivos. En cuanto a los resultados microbiológicos se comprobó que el principal colonización de cáncer cervical-vaginal fueron los Bacilos sugestivos de Gardnerella/Mobiluncus con 21,8%, seguido de Trichomonas vaginalis 12% y Cándida sp 5,8%. Las frecuencias de las muestras con atipia celular se registraron tasas de 4,1% para Atipias de significado indeterminado; Lesiones Intraepiteliales de bajo grado 3,2% y Lesiones Intraepiteliales de alto grado 2,5%. La conclusión es la importancia de la detección del cáncer cervical en las cárceles de mujeres, así como la inclusión de los enfermeros en este entorno al tiempo que garantiza una calidad y una atención individualizada a las mujeres presas.Objetivou-se analisar os resultados dos exames citopatológicos de mulheres privadas de liberdade. Estudo documental

Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.

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Ardighieri, Laura; Mori, Luigi; Conzadori, Sara; Bugatti, Mattia; Falchetti, Marcella; Donzelli, Carla Maria; Ravaggi, Antonella; Odicino, Franco E; Facchetti, Fabio

2016-07-01

Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81 %). In 10 patients (63 %), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.

Squamous cell dysplasia in the proximal rectum of three patients treated for ulcerative colitis on immunomodulators.

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Connolly, James G; Goldstone, Stephen E

2017-05-01

Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.

Utilidade da citologia anal no rastreamento dos homens heterossexuais portadores do HPV genital Anal cytology for screening heterosexual men harboring genital HPV infection

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Raphael Marianelli

2010-09-01

Full Text Available Os papilomavírus humanos (HPV de alto risco estão fortemente relacionados à etiologia do carcinoma espinocelular (CEC anogenital e suas lesões precursoras. O HPV-16 é o tipo mais freqüente, estando presente em até 87% dos CEC do canal anal HPV-positivo. Apesar de ser relativamente raro, vem sendo cada vez mais diagnosticado, nas últimas décadas, sobretudo em indivíduos do sexo masculino. A incidência é ainda mais elevada nos grupos considerados de risco, particularmente, os homens e as mulheres HIV-positivo e os homens que fazem sexo com homens (HSH. Grande parte das pesquisas direcionadas à infecção anal pelo HPV e sua relação com neoplasia intraepitelial-anal (NIA e com o carcinoma esteve focada nos grupos de risco. Pouco interesse vem sendo destinado à investigação dos homens heterossexuais. Estudos epidemiológicos da prevalência da infecção pelo HPV em homens, mostraram que os heterossexuais masculinos apresentavam infecção anal pelo HPV em até 12%. As Sociedades médicas e os especialistas recomendam o rastreamento dos portadores de imunodepressão e dos HSH com citologia do raspado do canal anal. Entretanto, até o momento, não há recomendação de rastreamento para homens que fazem sexo com mulheres.The oncogenic human papillomaviruses (HPV are straightly associated with anogenital cancer and dysplasia. The HPV-16 is the most common type, isolated in 87% of the HPV-positive anal squamous cell carcinoma (SCC. Despite being a rare tumor, the incidence of SCC has increased in the last decades, especially in males. Incidence is particularly high amongst men who have sex with men (MSM and among HIV infected men and women. For decades anogenital HPV researches have largely focused risk groups. Poor interest was intended to men who have sex with women (MSW. Prevalence studies of HPV infection in MSW have demonstrated that anal infection was identified in as far as 12%. Medical societies and specialists recommend anal

Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

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Lee, Andrew Y.; Golden, Daniel W. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Bazan, Jose G. [Department of Radiation Oncology, The Ohio State University, Columbus, Ohio (United States); Kopec, Malgorzata; Pelizzari, Charles A. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Aggarwal, Sonya; Chang, Daniel T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

2017-02-01

Purpose: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials: Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Results: Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). Conclusions: Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total “marrow reserve” can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence.

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Castellanos, Mario R; Szerszen, Anita; Gundry, Stephen; Pirog, Edyta C; Maiman, Mitchell; Rajupet, Sritha; Gomez, John Paul; Davidov, Adi; Debata, Priya Ranjan; Banerjee, Probal; Fata, Jimmie E

2015-07-25

Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit grayscale fluorescence images were used for image analysis. We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis.

Anal cancer precursor lesions in HIV-positive and HIV-negative patients seen at a tertiary health institution in Brazil Lesões precursoras do câncer anal em pacientes HIV-positivos e HIV-negativos atendidos numa instituição de saúde terciária no Brasil

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Ivan Tramujas da Costa e Silva

2011-02-01

Full Text Available Purpose: To investigate the prevalence of anal squamous intraepithelial lesions (ASIL or anal cancer in patients attended at the Tropical Medicine Foundation of Amazonas. Methods: 344 patients consecutively attended at the institution, in 2007/2008, were distributed in the following strata according to presence/abscense of at risk conditions for anal cancer: Group 1 _ HIV-positive men-who-have-sex-with-men (101; Group 2 _ HIV-positive females (49; Group 3 _ patients without any at risk condition for anal cancer (53; Group 4 _ HIV-positive heterosexual men (38; Group 5 _ HIV-negative patients, without anoreceptive sexual habits, but with other at risk conditions for anal cancer (45; Group 6 _ HIV-negative men-who-have-sex-with-men (26; and Group 7 _ HIV-negative anoreceptive females (32. The histopathological results of biopsies guided by high-resolution anoscopy were analyzed by frequentist and bayesian statistics in order to calculate the point-prevalence of ASIL/cancer and observe any eventual preponderance of one group over the other. Results: The point-prevalence of ASIL for all the patients studied was 93/344 (27%, the difference between HIV-positive and negative patients being statistically significant (38.3% versus 13.5%; p Objetivo: Investigar a prevalência de lesões intraepiteliais escamosas anais (ASIL ou câncer anal em pacientes atendidos na Fundação de Medicina Tropical do Amazonas. Métodos: 344 pacientes consecutivamente atendidos na instituição, em 2007/2008, foram distribuídos nos seguintes estratos conforme a presença/ausência de fatores de risco para o câncer anal: Grupo 1 _ homens-que-fazem-sexo-com-homens HIV-positivos (101; Grupo 2 _ mulheres HIV-positivas (49; Grupo 3 _ pacientes sem condição de risco para o câncer anal (53; Grupo 4 _ homens heterossexuais HIV-positivos (38; Grupo 5 _ pacientes HIV-negativos, sem hábitos sexuais anorreceptivos, mas com outras condições de risco para o câncer anal (45

A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.

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Sherman-Baust, Cheryl A; Kuhn, Elisabetta; Valle, Blanca L; Shih, Ie-Ming; Kurman, Robert J; Wang, Tian-Li; Amano, Tomokazu; Ko, Minoru S H; Miyoshi, Ichiro; Araki, Yoshihiko; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Morin, Patrice J

2014-07-01

Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histological analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal-appearing p53-positive epithelium that are similar to 'p53 signatures' in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these non-invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and wild-type (WT) C57BL/6. One of these genes, Top2a, which encodes topoisomerase IIα, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse STICs but not in the surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as

Concurrent Chemoradiotherapy With 5-Fluorouracil and Mitomycin C for Invasive Anal Carcinoma in Human Immunodeficiency Virus-Positive Patients Receiving Highly Active Antiretroviral Therapy

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Fraunholz, Ingeborg; Weiss, Christian; Eberlein, Klaus; Haberl, Annette; Roedel, Claus

2010-01-01

Purpose: To report the clinical outcomes of chemoradiotherapy (CRT) for anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. Patients and Methods: Between 1997 and 2008, 21 HIV-positive patients who were receiving highly active antiretroviral therapy were treated with CRT (50.4 Gy at 1.8 Gy/fraction plus a 5.4-10.8-Gy external boost; 5-fluorouracil, 1,000 mg/m 2 , Days 1-4 and 29-32; and mitomycin C, 10 mg/m 2 , Days 1 and 29). A retrospective analysis was performed with respect to the tumor response, local control, cancer-specific and overall survival, and toxicity. The immunologic parameters, including pre- and post-treatment CD4 count, viral load, and acquired immunodeficiency syndrome-specific morbidity was recorded during follow-up (median, 53 months; range, 10-99). Results: CRT could be completed in all 21 patients with a reduction in the chemotherapy dose and/or interruption of radiotherapy in 5 and 5 cases, respectively. Acute Grade 3 toxicity occurred in 8 (38%) of the 21 patients. A complete response was achieved in 17 patients (81%), and tumor persistence or early progression was noted in 4 (19%). Six patients (29%) died, 5 of cancer progression and 1 of treatment-related toxicity. The 5-year local control, cancer-specific, and overall survival rate was 59%, 75%, and 67%, respectively. The median CD4 count significantly decreased from 347.5 cells/μL before CRT to 125 cells/μL 3-7 weeks after CRT completion (p <.001). In 6 (32%) of 19 patients, an increase of the HIV viral load was noted. Both parameters returned to the pretreatment values with additional follow-up. Conclusion: Our data have confirmed that in the highly active antiretroviral therapy era, HIV-related anal cancer can be treated with standard CRT without dose reductions. Close surveillance of the immunologic parameters is necessary.

Comparison of telomerase activity in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic hyperplasia

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Soleiman Mahjoub

2006-11-01

Full Text Available BACKGROUND: Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA on chromosome ends. The enzyme is important for the immortalization of cancer cells because it maintains the telomeres. METHODS: Telomerase activity (TA was measured by fluorescence-based telomeric repeat amplification protocol (FTRAP assay in prostate carcinoma and benign prostatic hyperplasia (BPH. RESULTS: TA was present in 91.4% of 70 prostate cancers, 68.8% of 16 prostatic intraepithelial neoplasia (PIN, 43.3% of 30 BPH*, 21.4% of 14 atrophy and 20% of 15 normal samples adjacent to tumor. There was not any significant correlation between TA, histopathological tumor stage or gleason score. In contrast to high TA in the BPH* tissue from the cancer-bearing gland, only 6.3% of 32 BPH specimens from patients only diagnosed with BPH were telomerase activity-positive. CONCLUSIONS: These results indicate that TA is present in most prostate cancers. The high rate of TA in tissue adjacent to tumor may be attributed either to early molecular alteration of cancer that was histologically unapparent, or to the presence of occult cancer cells. Our findings suggest that the re-expression of telomerase activity could be one step in the transformation of BPH to PIN. KEY WORDS: Telomerase activity, prostate cancer, prostatic intraepithelial neoplasia, benign prostatic hyperplasia.

The importance of ultrasound findings in the study of anal pain Importancia de los hallazgos ecográficos en el dolor anal

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A. M. Vieira

2010-05-01

Full Text Available Objective: endoanal ultrasonography can detect organic causes of anal pain without pathology on physical examination. The aim of this study is to evaluate the importance of endoanal ultrasonography in the diagnosis and therapeutic management of idiopathic and functional anal pain. Material and methods: retrospective study, between 15 March 2005 and 15 June 2008, of all patients with proctalgia and normal examination or with alterations not responsible for anal pain at proctologic exam that have undergone an endoanal ultrasonography. Results: a total of 90 patients were analyzed, with a mean age of 50.5 years, 58% were female. Twenty-three patients had functional anal pain clinic criteria. Endoanal ultrasonography revealed alterations in 49% of patients. The primary findings were changes in sphincters in 14 patients, followed by anal sepsis in 12 patients, anal fissure in 10 patients, perirectal lesions in 6 patients and ulcer of the anal canal in 2 patients. Of the patients with sphincter defects, 5 patients had criteria of chronic anal pain. In this group of patients, no differences were found in manometric and defecographic results between the different ultrasound abnormalities. Conclusions: the endoanal ultrasonography detected occult organic lesions to proctologic examination, in half the patients with anal pain. Ultrasound abnormalities were found in 22% of patients with functional anal pain. However, there was no correlation between ultrasound findings and physiological studies, and therefore could not find etiological or pathogenic factors of functional anal pain.Objetivo: la ecografía endoanal puede detectar causas orgánicas en el dolor anal sin patología en la exploración física. El objetivo de este estudio es evaluar la importancia de la ecografía endoanal en el diagnóstico y en el abordaje terapéutico del dolor anal idiopática y funcional. Material y métodos: estudio retrospectivo realizado entre el 15 de marzo de 2005 y el

Histological outcomes in conventional cervical cytology for invasive carcinoma: not always cancer.

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Peixoto Pereira, Flávia Regina; Soares, Leila Cristina; de Oliveira, Marco Aurélio Pinho

2017-11-01

The value of cytology for the detection of invasive cancer remains unknown. We performed a retrospective cohort study with 884 patients diagnosed of premalignant lesions and invasive carcinoma in cytology. 382 (43.2%) of them had cytological results of high-grade squamous intraepithelial lesions (HSIL), 244 (27.6%) showed low-grade squamous intraepithelial lesions (LSIL), 120 (13.6%) patients had atypical squamous cells of undetermined significance (ASC-US), 67 (7.6%) patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 38 (4.3%) had invasive carcinoma and 33 (3.7%) patients presented with atypical glandular cells (ACG). From 38 patients with cytological results of invasive carcinoma, 24 had confirmatory histological results (63.2%). The other 14 had 4 benign lesions and 10 HSIL. The predictive positive value (PPV) was 63.2%. Cytology results of carcinoma do not confer a definitive diagnosis of invasive lesion, but it is strongly an indication of, at least, a precancerous lesion.

[Categorization of uterine cervix tumors : What's new in the 2014 WHO classification].

Science.gov (United States)

Lax, S F; Horn, L-C; Löning, T

2016-11-01

In the 2014 WHO classification, squamous cell precursor lesions are classified as low-grade and high-grade intraepithelial lesions. LSIL corresponds to CIN1, HSIL includes CIN2 and CIN3. Only adenocarcinoma in situ (AIS) is accepted as precursor of adenocarcinoma and includes the stratified mucin-producing intraepithelial lesion (SMILE). Although relatively rare, adenocarcinoma and squamous cell carcinoma can be mixed with a poorly differentiated neuroendocrine carcinoma. Most cervical adenocarcinomas are low grade and of endocervical type. Mucinous carcinomas show marked intra- and extracellular mucin production. Almost all squamous cell carcinomas, the vast majority of adenocarcinomas, and many rare carcinoma types are HPV related. For low grade endocervical adenocarcinomas, the pattern-based classification according to Silva should be reported. Neuroendocrine tumors are rare and are classified into low-grade and high-grade, whereby the term carcinoid is still used.

Clinical and molecular features of high-grade osteosarcoma

NARCIS (Netherlands)

Anninga, Jakob Klaas

2013-01-01

It can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant chemotherapy should be combined with radical surgery, irrespective the localization. There are only 4 effective

Long-Term Follow-Up of a Phase II Trial of High-Dose Radiation With Concurrent 5-Fluorouracil and Cisplatin in Patients With Anal Cancer (ECOG E4292)

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Chakravarthy, A. Bapsi, E-mail: bapsi.chak@vanderbilt.edu [Vanderbilt University Medical Center, Nashville, TN (United States); Catalano, Paul J. [Dana-Farber Cancer Institute, Boston, MA (United States); Martenson, James A. [Mayo Clinic, Rochester, MN (United States); Mondschein, Joshua K. [Vanderbilt University Medical Center, Nashville, TN (United States); Wagner, Henry [Pennsylvania State Hershey Cancer Institute, Hershey, PA (United States); Mansour, Edward G. [Case Western Reserve University, Cleveland, OH (United States); Talamonti, Mark S. [University of Chicago Pritzker School of Medicine, Evanston, IL (United States); Benson, Al Bowen [Northwestern University, Chicago, IL (United States)

2011-11-15

Purpose: Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. Methods and Materials: Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m{sup 2}/day on Days 1 to 4 and cisplatin 75 mg/m{sup 2} on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. Results: Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. Conclusions: Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.

Anal Itching

Science.gov (United States)

... has many possible causes, such as skin problems, hemorrhoids, and washing too much or not enough. If ... dermatitis. Other medical conditions. These include chronic diarrhea, hemorrhoids, anal tumors and diseases that affect the whole ...

High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

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Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

2015-01-01

Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

Developmental changes in intraepithelial T lymphocytes and NK cells in the small intestine of neonatal rats.

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Pérez-Cano, Francisco J; Castellote, Cristina; González-Castro, Ana M; Pelegrí, Carme; Castell, Margarida; Franch, Angels

2005-11-01

The main objective of this study was to characterize developmental changes in small intestinal intraepithelial lymphocyte (IEL) subpopulations during the suckling period, thus contributing to the understanding of the development of diffuse gut-associated lymphoid tissue (GALT) and to the identification of early mechanisms that protect the neonate from the first contact with diet and gut microbial antigens. The study was performed by double labeling and flow cytometry in IEL isolated from the proximal and distal small intestine of 1- to 21-d-old Lewis rats. During the suckling period, intraepithelial natural killer (NK) cells changed from a typical systemic phenotype, CD8+, to a specific intestinal phenotype, CD8-. Analysis of CD8+ IEL revealed a progressive increase in the relative number of CD8+ IEL co-expressing TCRalphabeta, cells associated with acquired immunity, whereas the percentage of CD8+ cells expressing the NK receptor, i.e. cells committed to innate immunity, decreased. At weaning, IEL maturity was still not achieved, as revealed by a phenotypic pattern that differed from that of adult rats. Thus, late after weaning, the regulatory CD8+CD4+ T IEL population appeared and the NK population declined. In summary, the intestinal intraepithelial compartment undergoes changes in its lymphocyte composition associated with the first ingestion of food. These changes are focused on a relatively high proportion of NK cells during the suckling period, and after weaning, an expansion of the regulatory CD8+CD4+ T cells.

Multiparametric Magnetic Resonance Imaging for Discriminating Low-Grade From High-Grade Prostate Cancer

NARCIS (Netherlands)

Vos, E.K.; Kobus, T.; Litjens, G.J.S.; Hambrock, T.; Hulsbergen-van de Kaa, C.A.; Barentsz, J.O.; Maas, M.C.; Scheenen, T.W.J.

2015-01-01

The aim of this study was to determine and validate the optimal combination of parameters derived from 3-T diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for discriminating low-grade from high-grade prostate cancer (PCa).The study was

Terahertz reflectometry imaging for low and high grade gliomas

Science.gov (United States)

Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

2016-01-01

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

Chemoradiotherapy in patients with anal cancer: Impact of length of unplanned treatment interruption on outcome

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Meyer, Andreas; Meier Zu Eissen, Juergen; Karstens, Johann H.; Bremer, Michael [Medical School Hannover (Germany). Dept. of Radiation Oncology

2006-09-15

The aim of this retrospective analysis was to evaluate feasibility and effectiveness of definitive chemoradiotherapy without split-course technique in anal cancer patients. From 1993 to 2003, 81 patients were treated; 13 were excluded due to various chemotherapeutic regimes, thus 68 patients were analysed. In case of acute grade 3 toxicities, treatment was halted until improvement or resolution independent of dose. Short interruption was defined as completing treatment without exceeding eight cumulative treatment days beyond scheduled plan, other patients were considered to have had prolonged interruption. Median follow-up was 46 months. Median overall treatment time was 53 days corresponding to an interruption of eight cumulative treatment days. Thirty-five patients (51%) had treatment interruption of <8 days. No acute grade 4 toxicities were observed; one fatality occurred during treatment due to ileus-like symptoms according to acute grade 5 toxicity. Comparing patients with short vs. prolonged interruption 5-year actuarial rates for local control were 85% vs. 81% (p{approx}0.605) and for colostomy-free survival 85% vs. 87% (p{approx}0.762), respectively. Chemoradiotherapy with short individualised treatment interruptions seems to be feasible with acceptable acute or late toxicities. Treatment is highly effective in terms of local control and colostomy-free survival.

Early discharge after external anal sphincter repair

DEFF Research Database (Denmark)

Rosenberg, J; Kehlet, H

1999-01-01

PURPOSE: The aim of this study was to describe an accelerated-stay program for repair of the external anal sphincter. METHODS: Twenty consecutive patients undergoing overlapping repair of the external anal sphincter were included in the study. Effect parameters were length of hospitalization....... CONCLUSION: We have described a safe accelerated-stay program (24 to 48 hours) for overlapping repair of external anal sphincter....

Ki-67 labeling index as an adjunct in the diagnosis of serous tubal intraepithelial carcinoma.

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Kuhn, Elisabetta; Kurman, Robert J; Sehdev, Ann Smith; Shih, Ie-Ming

2012-09-01

There is mounting evidence that serous tubal intraepithelial carcinoma (STIC) may be the immediate precursor of ovarian high-grade serous carcinoma (HGSC) but the criteria for its diagnosis are not well established as highlighted in a recent study showing that interobserver reproducibility, even among expert gynecologic pathologists, was moderate at best. Given the clinical significance of a diagnosis of STIC in a patient who has no other evidence of ovarian carcinoma, this is a serious issue that we felt needed to be addressed. Although it is not clear, at this time, whether such a patient should or should not be treated, the importance of an accurate and reproducible diagnosis of precursors of ovarian carcinoma cannot be underestimated. We hypothesized that an elevated Ki-67 labeling index may aid the diagnosis of STIC. Accordingly, we compared the Ki-67 index of STIC and HGSC to normal fallopian tube epithelium (FTE) in the same patients and to a control group of patients without carcinoma, matched for age. A total of 41 STICs were analyzed, of which 35 were associated with a concurrent HGSC. In FTE, immunoreactivity for Ki-67 was restricted to a few scattered cells (mean 2.0%). No statistically significant difference was found between patients with and without HGSC (P>0.05). However, both STICs and HGSC had significantly higher Ki-67 indices than normal FTE (PSTICs uniformly had an elevated Ki-67 labeling index that ranged from 11.7% to 71.1% (average 35.6%). There was no correlation of the Ki-67 labeling index in the STICs and the associated HGSC, as the labeling index was lower in STIC in 18/35 (51.4%) whereas it was higher in 17/35 (48.6%) (P=0.86). In conclusion, the findings in this study indicate that compared with FTE, STICs have a significantly higher Ki-67 index similar to HGSC. Accordingly, the Ki-67 index can aid the diagnosis of intraepithelial tubal proliferations suspicious for STIC. Therefore, we propose that a Ki-67 index of 10% is a useful

Are the uterine serous carcinomas underdiagnosed? Histomorphologic and immunohistochemical correlates and clinical follow up in high-grade endometrial carcinomas initially diagnosed as high-grade endometrioid carcinoma.

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Hu, Shaomin; Hinson, Jeff L; Matnani, Rahul; Cibull, Michael L; Karabakhtsian, Rouzan G

2018-02-01

Histologic subclassification of high-grade endometrial carcinomas can sometimes be a diagnostic challenge when based on histomorphology alone. Here we utilized immunohistochemical markers to determine the immunophenotype in histologically ambiguous high-grade endometrial carcinomas that were initially diagnosed as pure or mixed high-grade endometrioid carcinoma, aiming to determine the utility of selected immunohistochemical panel in accurate classification of these distinct tumor types, while correlating these findings with the clinical outcome. A total of 43 high-grade endometrial carcinoma cases initially classified as pure high-grade endometrioid carcinoma (n=32), mixed high-grade endometrioid carcinoma/serous carcinoma (n=9) and mixed high-grade endometrioid carcinoma/clear cell carcinoma (n=2) were retrospectively stained with a panel of immunostains, including antibodies for p53, p16, estrogen receptor, and mammaglobin. Clinical follow-up data were obtained, and stage-to-stage disease outcomes were compared for different tumor types. Based on aberrant staining for p53 and p16, 17/43 (40%) of the high-grade endometrial carcinoma cases initially diagnosed as high-grade endometrioid carcinoma were re-classified as serous carcinoma. All 17 cases showed negative staining for mammaglobin, while estrogen receptor was positive in only 6 (35%) cases. The remaining 26 cases of high-grade endometrioid carcinoma showed wild-type staining for p53 in 25 (96%) cases, patchy staining for p16 in 20 (77%) cases, and were positive for mammaglobin and estrogen receptor in 8 (31%) and 19 (73%) cases, respectively, thus the initial diagnosis of high-grade endometrioid carcinoma was confirmed in these cases. In addition, the patients with re-classified serous carcinoma had advanced clinical stages at diagnosis and poorer overall survival on clinical follow-up compared to that of the remaining 26 high-grade endometrioid carcinoma cases. These results indicate that selected

Population-based prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark

DEFF Research Database (Denmark)

Kjaer, Susanne K.; Breugelmans, Gabrielle; Munk, Christian

2008-01-01

/11. Prevalence of high-risk HPV types increased from 19.2% in women with normal cytology to 100% in women with cervical intraepithelial neoplasia grade 3 (CIN3)/cervical cancer. HPV 16 was the most prevalent type (6.0% of all women), and was also the most prevalent in women with HSIL (35.1%) and CIN3 (53......-grade squamous intraepithelial lesion and 1.6% had high-grade squamous intraepithelial lesion (HSIL). The HPV prevalence was 26.4% with a peak in women 20-24 years (50.2%) and then decreased without a second peak in older women. Among the youngest women (15-19 years), 14% had HPV 16/18 and 16% had HPV 6.......2%). Other common HPV types in women with CIN3 included HPV 52, 51, 31, 33 and 18. HPV 16/18 alone was present in 23% of CIN3 lesions and 67% of cervical cancers, and HPV 16/18 together with other high-risk HPV types was present in 41% of CIN3 lesions. This suggests that an efficacious HPV 16/18 vaccine...

Mode of delivery after obstetric anal sphincter injury.

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Karmarkar, Roopali; Bhide, Alka; Digesu, Alex; Khullar, Vik; Fernando, Ruwan

2015-11-01

To assess the effect of vaginal delivery and caesarean section on faecal symptoms and structure and function of anal sphincter in women who sustained obstetric anal sphincter injuries (OASIS) in their previous pregnancy and were advised about the mode of delivery based on faecal incontinence symptoms, anal manometry and endoanal ultrasound. It is a descriptive study on a cohort of women who had OASIS from 2006 to 2013. They were assessed after OASIS and during subsequent pregnancy with a questionnaire, endoanal ultrasound and anal manometry. Vaginal delivery was recommended to asymptomatic women with normal investigations. Elective caesarean section was recommended to women with faecal symptoms, anal sphincter defects of more than 30° or low resting or incremental anal pressures. All women were reassessed after subsequent delivery. Fifty women who had pregnancies after OASIS, were seen after OASIS, during subsequent pregnancy and after the second delivery. 15 women had faecal symptoms after OASIS. The external, internal and combined anal sphincter defects were seen in 13, 11 and 9 women respectively. Low resting and incremental pressure were seen in 15 and 11 women respectively. Caesarean section was done in 22 women and 28 women delivered vaginally. Worsening of faecal symptoms and reduction in anal pressures were not observed in planned vaginal delivery or elective caesarean section groups. Faecal symptoms were worse with reduced anal pressures in three women from the planned caesarean section group. One of the women had a vaginal delivery and two women had emergency caesarean section at 7cm and 10cm dilatation. There were no new sphincter defects or recurrent OASIS in any of the women in the study group. Decision about the mode of delivery of pregnancy after OASIS based on symptoms, anal manometry and endoanal ultrasound helps in preserving the anal sphincter function and avoiding unnecessary caesarean sections. Further follow-up of these patients is essential

Incidental Serous Tubal Intraepithelial Carcinoma and Non-Neoplastic Conditions of the Fallopian Tubes in Grossly Normal Adnexa: A Clinicopathologic Study of 388 Completely Embedded Cases.

Science.gov (United States)

Seidman, Jeffrey D; Krishnan, Jayashree; Yemelyanova, Anna; Vang, Russell

2016-09-01

Serous tubal intraepithelial carcinoma (STIC), the putative precursor of the majority of extrauterine high-grade serous carcinomas, has been reported in both high-risk women (those with a germline BRCA mutation, a personal history of breast carcinoma, and/or family history of breast or ovarian carcinoma) and average risk women from the general population. We reviewed grossly normal adnexal specimens from 388 consecutive, unselected women undergoing surgery, including those with germline BRCA mutation (37 patients), personal history of breast cancer or family history of breast/ovarian cancer (74 patients), endometrial cancer (175 patients), and a variety of other conditions (102 patients). Among 111 high-risk cases and 277 non-high-risk cases, 3 STICs were identified (0.8%), all in non-high-risk women (high risk vs. non-high risk: P=not significant). STIC was found in 2 women with nonserous endometrial carcinoma and 1 with complex atypical endometrial hyperplasia. Salpingoliths (mucosal calcifications), found in 9% of high-risk cases, and fimbrial adenofibromas in 9.9% of high-risk cases, were significantly more common in high-risk as compared with non-high-risk women (1.8% and 2.5%, respectively; PSTIC and endometrial hyperplasia and carcinoma, and clarify the frequency of non-neoplastic tubal findings in grossly normal fallopian tubes.

An automated quantitative DNA image cytometry system detects abnormal cells in cervical cytology with high sensitivity.

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Wong, O G; Ho, M W; Tsun, O K; Ng, A K; Tsui, E Y; Chow, J N; Ip, P P; Cheung, A N

2018-03-26

To evaluate the performance of an automated DNA-image-cytometry system as a tool to detect cervical carcinoma. Of 384 liquid-based cervical cytology samples with available biopsy follow-up were analyzed by both the Imager System and a high-risk HPV test (Cobas). The sensitivity and specificity of Imager System for detecting biopsy proven high-grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low-grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high-risk HPV test agreed in 69.43% (268) of all samples. The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2-3+) lesions. © 2018 John Wiley & Sons Ltd.

Analysis and description of disease-specific quality of life in patients with anal fistula.

Science.gov (United States)

Ferrer-Márquez, Manuel; Espínola-Cortés, Natalia; Reina-Duarte, Ángel; Granero-Molina, José; Fernández-Sola, Cayetano; Hernández-Padilla, José Manuel

2018-04-01

In patients diagnosed with anal fistula, knowing the quality of life specifically related to the disease can help coloproctology specialists to choose the most appropriate therapeutic strategy for each case. The aim of our study is to analyzse and describe the factors related to the specific quality of life in a consecutive series of patients diagnosed with anal fistula. Observational, cross-sectional study carried out from March 2015 to February 2017. All patients were assessed in the colorectal surgery unit of a hospital in southeast of Spain. After performing an initial anamnesis and a physical examination, patients diagnosed with anal fistula completed the Quality of Life in Ppatients with Anal Fistula Questionnaire (QoLAF-Q). This questionnaire specifically measures quality of life in people with anal fistula and its score range is the following: zero impact = 14 points, limited impact = 15 to 28 points, moderate impact = 29 to 42 points, high impact = 43 to 56 points, and very high impact = 57 to 70 points. A total of 80 patients were included. The median score obtained in the questionnaire for the sample studied was 34.00 (range=14-68). Statistically significant differences between patients with "primary anal fistula" (n=65) and "recurrent anal fistula" (n=15) were observed (mean rank=42.96 vs. mean rank=29.83, p=0.048). Furthermore, an inverse proportion (P=.016) between "time with clinical symptoms" and "impact on quality of life" was found (5 years: mean rank = 19.00). There were no statistically significant differences (P=.149) between quality of life amongst patients diagnosed with complex (mean rank = 36.13) and simple fistulae (mean rank = 43.59). Anal fistulae exert moderate-high impact on patients' quality of life. "Shorter time experiencing clinical symptoms" and the "presence of primary fistula" are factors that can be associated with worse quality of life. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm improves quality of life in recessive dystrophic epidermolysis bullosa

Directory of Open Access Journals (Sweden)

Cassandra Chaptini, MBBS

2015-12-01

Full Text Available We report a 20-year-old female with generalized, severe, recessive dystrophic epidermolysis bullosa who developed secondary chronic anal fissures. This resulted in anal sphincter spasm and severe, disabling pain. She was treated with five botulinum toxin A injections into the internal anal sphincter over a period of 2 years and gained marked improvement in her symptoms. This case demonstrates the successful use of botulinum toxin A injections to relieve anal sphincter spasm and fissuring, with long-term improvement.

NOVEL EPIGENETIC CHANGES IN CDKN2A ARE ASSOCIATED WITH PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA

Science.gov (United States)

Wijetunga, N. Ari; Belbin, Thomas J.; Burk, Robert D.; Whitney, Kathleen; Abadi, Maria; Greally, John M.; Einstein, Mark H.; Schlecht, Nicolas F.

2016-01-01

Objective To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16INK4A and p14ARF proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. Methods We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. Results In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. Conclusion Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16INK4A/p14ARF expression prior to development of malignant disease. PMID:27401842

Novel epigenetic changes in CDKN2A are associated with progression of cervical intraepithelial neoplasia.

Science.gov (United States)

Wijetunga, N Ari; Belbin, Thomas J; Burk, Robert D; Whitney, Kathleen; Abadi, Maria; Greally, John M; Einstein, Mark H; Schlecht, Nicolas F

2016-09-01

To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16(INK4A)/p14(ARF) expression prior to development of malignant disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of high-grade dysplasia in Barrett's esophagus.

Science.gov (United States)

Palley, S L; Sampliner, R E; Garewal, H S

1989-08-01

When Barrett's esophagus is complicated by adenocarcinoma, surgery is indicated in appropriate patients. Until now, high-grade dysplasia in Barrett's esophagus has been managed in a similar fashion. We explore this approach and review reported cases of high-grade dysplasia to suggest guidelines for collection of data to make future clinical decisions more rational.

Correlates of unprotected anal intercourse: the influence of anal sex position among men who have sex with men in Beijing, china.

Science.gov (United States)

Zhang, Heng; Lu, Hongyan; Pan, Stephen W; Xia, Dongyan; Zhao, Yuejuan; Xiao, Yan; He, Xiong; Yue, Hai; Sun, Zheya; Xu, Yunan; Ruan, Yuhua; Shao, Yiming

2015-02-01

Understanding barriers to consistent condom use among men who have sex with men (MSM) requires consideration of the context in which risk behaviors occur. Anal sex position is one such context. This pooled cross-sectional study used survey data from 1,230 MSM and their 2,618 reported male sexual partnerships. Overall, nearly half of the participants engaged in unprotected anal intercourse (UAI) with at least one of upto three partners in the past 6 months. "Insertive" men engaged in less UAI (39 %) than "receptive" (53 %) or "versatile" (51 %) men. Regardless of sexual position, UAI was associated with cohabiting with a male or female partner and perceiving great or moderate risk of HIV from male contact at the individual level, and steady (vs. casual) partnership at the dyad level. However, early MSM anal sex debut, high number of male partners, alcohol use, receiving and buying condoms, HIV testing, and MSM sex-seeking venues were found to be only statistically significantly correlated with UAI among some but not all sexual positions, implying that interventions to increase condom use should take into account how anal sex position may influence willingness and ability to engage in safer sex. Dyad level data appear to provide additional insight into the influence of sexual positions, and should be used to complement individual data for future intervention designs.

Viral load and genomic integration of HPV 16 in cervical samples from HIV-1-infected and uninfected women in Burkina Faso.

Science.gov (United States)

Rousseau, Marie-Noelle Didelot; Costes, Valérie; Konate, Issouf; Nagot, Nicolas; Foulongne, Vincent; Ouedraogo, Abdoulaye; Van de Perre, Philippe; Mayaud, Philippe; Segondy, Michel

2007-06-01

The relationships between human papillomavirus type 16 (HPV 16) viral load, HPV 16 integration status, human immunodeficiency virus type 1 (HIV-1) status, and cervical cytology were studied among women enrolled in a cohort of female sex workers in Burkina Faso. The study focused on 24 HPV 16-infected women. The HPV 16 viral load in cervical samples was determined by real-time PCR. Integration ratio was estimated as the ratio between E2 and E6 genes DNA copy numbers. Integrated HPV16 viral load was defined as the product of HPV 16 viral load by the integration ratio. High HPV 16 viral load and high integration ratio were more frequent among women with squamous intraepithelial lesions compared with women with normal cytology (33% vs. 11%, and 33% vs. 0%, respectively), and among women with high-grade squamous intraepithelial lesions compared with women without high-grade squamous intraepithelial lesions (50% vs. 17%, and 50% vs. 11%, respectively). High HPV 16 DNA load, but not high integration ratio, was also more frequent among HIV-1-positive women (39% vs. 9%; and 23% vs. 18%, respectively). The absence of statistical significance of these differences might be explained by the small study sample size. High-integrated HPV 16 DNA load was significantly associated with the presence of high-grade squamous intraepithelial lesions (50% vs. 5%, P = 0.03) in univariate and multivariate analysis (adjusted odds-ratio: 19.05; 95% confidence interval (CI), 1.11-328.3, P = 0.03), but not with HIV-1 or other high-risk HPV types (HR-HPV). Integrated HPV 16 DNA load may be considered as a useful marker of high-grade cervical lesions in HPV 16-infected women. (c) 2007 Wiley-Liss, Inc.

Clinical investigation of the safety and efficacy of a cervical intraepithelial neoplasia treatment using a hyperthermia device that uses heat induced by alternating magnetic fields

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Koizumi, Koji; Fujioka, Toru; Yasuoka, Toshiaki; Inoue, Aya; Uchikura, Yuka; Tanaka, Hiroki; Takagi, Katsuko; Mori, Miki; Koizumi, Masae; Hashimoto, Hisashi; Matsumoto, Takashi; Matsubara, Yuko; Matsubara, Keiichi; Nawa, Akihiro

2016-01-01

Multiple techniques have been used for the conservative treatment of high-grade cervical intraepithelial neoplasia (HG-CIN) in women of fertile age. Conization has been associated with stenosis of the cervix and a decrease in cervical mucus secretion, in addition to the increase in the risk of cervical canal shortening and problems during the perinatal period, including premature birth and premature rupture of membranes. Although the laser transpiration technique does not cause shortening of the cervical canal, it is associated with the recurrent risk of deep residual disease. The present study aimed to investigate the therapeutic safety and efficacy of the therapy performed using the transaction magnetic field induction heating device, AMTC400, in fertile patients with HG-CIN (excluding carcinoma in situ). Four premenopausal patients with CIN3 and high-risk human papilloma virus (HPV)-positive were treated using an AMTC400. Chronological colposcopic findings, high-risk HPV, final histological findings with conization and follow-up data were evaluated. All the treatments were successfully performed on the in-patients without anesthesia. Intra- and postoperative complications included minor pain and bleeding in all cases. Two of the cases (50%) were high-risk HPV-negative following the treatments. All cases exhibited a change in the observed color (to white), and subsequent epithelization following treatment. Although cytological analysis at 5 weeks following the treatment confirmed the cases were negative for intraepithelial lesions and malignancies, a definitive histology with conization 6 weeks following the treatment confirmed CIN1 and koilocytosis in all cases. The assessment of treatment effectiveness was determined as a moderate improvement in all cases. In conclusion, thermotherapy applied using AMTC400 represented a safe and effective treatment for HG-CIN in women of fertile age. However, additional improvements associated with the site of puncture needles

Surgical Treatment of Anal Stenosis with Diamond Flap Anoplasty Performed in a Calibrated Fashion.

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Gülen, Merter; Leventoğlu, Sezai; Ege, Bahadir; Menteş, B Bülent

2016-03-01

manner is a highly successful method for the treatment of anal stenosis caused by previous hemorrhoidectomy.

A New Method to Treat High Anal Fistula - Bidirectional Isobaric Drainage

DEFF Research Database (Denmark)

Zheng, Linghua; Wang, Yanmei; Zhao, Jingbo

2016-01-01

-category verbal rating scale, VRS), and the score of anal function (Wexner Incontinence Score) were quantitatively evaluated. Results: Comparison of the efficacy between two groups indicated that the complete cure rate differed significantly between two groups (P... in the Experimental group than in the Control group (PVRS and Wexner scores were significantly smaller in Experimental group than in Control group (P

Endometrial intraepithelial carcinoma: A case report and brief review

Directory of Open Access Journals (Sweden)

Ram Manisha

2008-10-01

Full Text Available This case report describes the precursor lesion of uterine papillary serous carcinoma (UPSC. A 65-year-old post-menopausal female presented with prolapse and vaginal discharge and underwent a hysterectomy revealing an atrophic endometrium, highly atypical endometrial glands, the lining cells of which showed pseudostratification, hobnailing, a high nuclear to cytoplasmic ratio, and prominent nucleoli. A p53 immunoreactivity score of 8 and a MIB-1 index of 80% was obtained leading to a diagnosis of endometrial intraepithelial carcinoma (EIC. Since serous EIC is commonly associated with extra-uterine serous carcinoma, it is a uniquely aggressive precursor lesion. Molecular studies support the hypothesis that EIC is a precursor of both uterine and extra-uterine invasive serous carcinomas. This is why the treatment protocol for EIC cases is total abdominal hysterectomy (TAH, accompanied by a staging procedure. In our patient, EIC was limited to the endometrium; associated with an excellent clinical outcome.

Electrocautery Superior to Topical Treatments for Precancerous Anal Lesions

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... Professional Anal Cancer Treatment Anal Cancer Prevention Research Electrocautery Superior to Topical Treatments for Precancerous Anal Lesions ... randomized clinical trial conducted in Amsterdam suggest that electrocautery is better than topical imiquimod or fluorouracil at ...

Pharmacokinetic MRI of the prostate. Parameters for differentiating low-grade and high-grade prostate cancer

International Nuclear Information System (INIS)

Franiel, T.; Taupitz, M.; Asbach, P.; Beyersdorff, D.; Luedemann, L.; Rost, J.

2009-01-01

Purpose: to investigate whether pharmacokinetic MRI parameters ''perfusion, blood volume, mean transit time (MTT), interstitial volume, permeability, extraction coefficient, delay, and dispersion'' allow the differentiation of low-grade (Gleason score ≤ 6) and high-grade (Gleason score ≥ 7) prostate cancer. Materials and method: forty-two patients with prostate cancer verified by biopsy (PSA 2.7 to 31.4ng/ml) and scheduled for prostatectomy underwent MRI at 1.5 Tesla using the dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence (temporal resolution, 1.65 s) and a combined endorectal body phased array coil. Parametric maps were computed using a sequential 3-compartment model and the corresponding post-processing algorithms. A total of 41 areas of prostate cancer (15 low-grade, 26 high-grade cancers) in 32 patients were able to be correlated with the prostatectomy specimens and were included in the analysis. Results: low-grade prostate cancers had a higher mean blood volume (1.76% vs. 1.64%, p = 0.039), longer MTT (6.39 s vs. 3.25 s, p -1 vs. 3.86 min -1 , p = 0.011) than high-grade cancers. No statistically significant difference was found for perfusion (p = 0.069), interstitial volume (p = 0.849), extraction coefficient (p = 0.615), delay (p = 0.489), and dispersion (p = 0.306). (orig.)

ATYPICAL MITOTIC FIGURES AND THE MITOTIC INDEX IN CERVICAL INTRAEPITHELIAL NEOPLASIA

NARCIS (Netherlands)

VANLEEUWEN, AM; PIETERS, WJLM; HOLLEMA, H; BURGER, MPM

1995-01-01

We surveyed cervical intraepithelial neoplasia (CIN) to quantify the proliferation rate and the presence of normal and atypical mitotic figures. In the cervical tissue specimens of 127 women with CIN, the area with the highest cell proliferation was identified and, at that site, the proliferation

Effectiveness of systematic alphanumeric coded endoscopy for diagnosis of gastric intraepithelial neoplasia in a low socioeconomic population.

Science.gov (United States)

Machaca Quea, Nancy Roxana; Emura, Fabian; Barreda Bolaños, Fernando; Salvador Arias, Yuliana; Arévalo Suárez, Fernando Antonio; Piscoya Rivera, Alejandro

2016-10-01

Background and study aims: In the Western world, gastric cancer (GC) usually presents at an advanced stage, carrying a high mortality rate. Studies have reported that 14 % to 26 % of GCs are missed at endoscopy up to 3 years before diagnosis. Systematic Alphanumeric Coded Endoscopy (SACE) has been proposed to improve quality of esophagogastroduodenoscopy (EGD) by facilitating a complete examination of the upper gastrointestinal tract. This prospective cross-sectional study was designed to determine the frequency of gastric intraepithelial neoplasia (GIN) by using the SACE approach in cohort of patients from low socioeconomic level. It also used non-targeted biopsies to evaluate the frequency of premalignant conditions. Patients and methods: A total of 601 consecutive asymptomatic or dyspeptic patients were enrolled between January 2013 and November 2014 at the Huacho regional hospital in Peru. The SACE method proposed by Emura et al, which divides the stomach into 5 regions and 21 areas, was routinely used for diagnosis. Biopsy samples were obtained from any endoscopically detected focal lesion. To evaluate gastric premalignant conditions, 4 non-targeted biopsies were taken. Results: A total of 573 patients were analyzed. The mean age was 57 years, and the female:male ratio was 1.9 : 1. In all cases, complete photo-documentation of the 21 gastric areas was achieved. The overall rate of detection of GIN was 2.8 %. Low-grade displasia, high-grade dysplasia, and adenocarcinoma were found in 13 (2.3 %), 2 (0.3 %), and 1 (0.2 %) of the patients, respectively. The prevalence of at least 1 premalignant condition was 31 %, and helicobacter pylori infection was found in 57 % of patients. Conclusions: Using the SACE approach and with proper training, we have reported herein a high frequency of GIN in patients from a low socioeconomic status. Gastric cancer detection can be improved in a Western endoscopy setting when SACE, as a screening method, is

Anal carcinoma and HIV infection: is it time for screening?

Science.gov (United States)

Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M

2014-03-01

A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented? Copyright © 2013 Elsevier España, S.L. All rights reserved.

Neuronal hyperplasia in the anal canal

DEFF Research Database (Denmark)

Fenger, C; Schrøder, H D

1990-01-01

In a consecutive series of minor surgical specimens from the anal canal, neuronal hyperplasia was found in nine of 56 haemorrhoidectomy specimens and in four of 23 fibrous polyps. In an additional series of 14 resections of the anal canal, neuronal hyperplasia was present in six cases, of which f...

Anal Cancer Treatment (PDQ®)—Patient Version

Science.gov (United States)

Anal cancer is uncommon, but often curable with treatment. Treatments include radiation therapy, chemotherapy, and surgery. Get detailed information about anal cancer including risk factors, symptoms, diagnosis, prognosis, and treatment in this expert-reviewed summary.

Ultraviolet B irradiation induces expansion of intraepithelial tumor cells in a tissue model of early cancer progression.

Science.gov (United States)

Mudgil, Adarsh V; Segal, Nadav; Andriani, Frank; Wang, Youai; Fusenig, Norbert E; Garlick, Jonathan A

2003-07-01

Ultraviolet B irradiation is thought to enable skin cancer progression as clones of genetically damaged keratinocytes escape apoptosis and expand at the expense of adjacent normal cells. Mechanisms through which potentially malignant cells in human skin undergo clonal expansion, however, are not well understood. The goal of this study was to characterize the role of ultraviolet B irradiation on the intraepithelial expansion of early stage human tumor cells in organotypic skin cultures. To accomplish this, we have studied the effect of ultraviolet B irradiation on organotypic cultures that were fabricated by mixing normal human keratinocytes with beta-galactosidase-marked, intraepithelial tumor cells (HaCaT-ras, clone II-4), which bear mutations in both p53 alleles and harbor an activated H-ras oncogene. We found that when organotypic mixtures were exposed to an ultraviolet B dose of 50 mJ per cm2, intraepithelial tumor cells underwent a significant degree of proliferative expansion compared to nonirradiated cultures. To understand this response, organotypic cultures of nor-mal keratinocytes were exposed to ultraviolet B and showed a dose-dependent increase in numbers of sunburn cells and TUNEL-positive cells although their proliferation was suppressed. In contrast, neither the apoptotic nor the proliferative response of II-4 cells was altered by ultraviolet B in organotypic cultures. The differential response of these cell types suggested that II-4 cells were resistant to ultraviolet-B-induced alterations, which allowed these intraepithelial tumor cells to gain a selective growth and survival advantage relative to neighboring normal cells. These findings demonstrate that ultraviolet B exposure can induce the intraepithelial expansion of apoptosis-resistant, p53-mutant, and ras-activated keratinocytes, suggesting that this agent can act to promote the early stages of epithelial carcinogenesis.

Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal carcinoma: Are there differences between HIV-positive and HIV-negative patients in the era of highly active antiretroviral therapy?

International Nuclear Information System (INIS)

Fraunholz, Ingeborg; Rabeneck, Daniela; Gerstein, Johanna; Jaeck, Katharina; Haberl, Annette; Weiss, Christian; Roedel, Claus

2011-01-01

Purpose: To report treatment compliance, toxicity and clinical outcome of chemoradiotherapy (CRT) for anal carcinoma in HIV-negative vs. HIV-positive patients treated with highly active antiretroviral therapy. Material and methods: Between 1997 and 2008, 25 HIV-positive and 45 HIV-negative patients received CRT (50.4 Gy at 1.8 Gy/fraction plus 5.4-10.8 Gy boost; 5-fluorouracil, 1000 mg/m 2 , Days 1-4 and 29-32, mitomycin C, 10 mg/m 2 , Days 1 and 29). Median follow-up was 51 (range, 3-235) months. Results: HIV-positive patients were significantly younger (mean age, 47 vs. 57 years, p < 0.001) and predominantly male (92% vs. 29%, p < 0.001). CRT could be completed in all patients with a reduction of chemotherapy and/or RT-interruption in 28% and 8%, respectively, in HIV-positive patients, and in 9% and 11%, respectively, in HIV-negative patients. Acute Grade 3/4-toxicity occurred in 44% vs. 49% (p = 0.79). Initial complete response (84% vs. 93%, p = 0.41), 5-year rates of local control (65% vs. 78%, p = 0.44), cancer-specific (78% vs. 90%, p = 0.17) and overall survival (71% vs. 77%, p = 0.76) were not significantly different. Conclusion: HIV-positive patients with anal cancer can be treated with standard CRT, with the same tolerability and toxicity as HIV-negative patients. Long-term local control and survival rates are not significantly different between these groups.

[High-grade pressure sores in frail older high-risk persons. A retrospective postmortem case-control-study].

Science.gov (United States)

Von Renteln-Kruse, W; Krause, T; Anders, J; Kühl, M; Heinemann, A; Püschel, K

2004-04-01

Some old persons at risk do develop, but others, at comparable risk, do not develop high-grade pressure sores. To evaluate potentially different risk factors, we performed a post mortem case-control study in old persons who developed high-grade pressure sores within six months until 14 days before death. Consecutive cases with pressure sores grade >/=3 and potential controls at comparably high risk for pressure sores were examined before cremation. After written informed consent had been obtained by the next relatives, all available nursing and medical records of the deceased were thoroughly evaluated. Cases and controls were matched according to age, gender, immobility, and cachexia.A total of 100 cases with 71 pressure sores grade 3 and 29 pressure sores grade 4 were compared to 100 controls with 27 pressure sores grade pressure sores in frail older high-risk persons. Sedative drug effects and impaired patient compliance with preventive and therapeutic measures may also be associated with the development of high-grade pressure sores in old persons at high risk.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

Science.gov (United States)

Molloy, M; Comer, R; Rogers, P; Dowling, M; Meskell, P; Asbury, K; O'Leary, M

2016-11-01

To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

Environmental exposure to cooking oil fumes and cervical intraepithelial neoplasm

International Nuclear Information System (INIS)

Wu, M.-T.; Lee, L.-H.; Ho, C.-K.; Wu, S.-C.; Lin, L.-Y.; Cheng, B.-H.; Liu, C.-L.; Yang, C.-Y.; Tsai, H.-T.; Wu, T.-N.

2004-01-01

The fumes from cooking oil, similar to cigarette smoke, contain numerous carcinogens such as polycyclic aromatic hydrocarbons, aromatic amines, nitro-polycyclic aromatic hydrocarbons, etc. In this study, we examined the association between exposure to cooking oil fumes and the risk of cervical intraepithelial neoplasm. The study population in this nested case-control study consisted of women above the age of 19 years living in Chia-Yi County, located in the southwestern Taiwan, who had received pap smear screening between October, 1999, and December, 2000 (n=32,466). The potential cases were women having lesions greater than cervical intraepithelium neoplasm II (≥CIN2) reconfirmed by cervical biopsy (n=116). The potential controls (case: control=1:2) were age-matched (±2 years) and residence-matched women who had normal pap smears within 6 months of the cases. In total, 100 cases and 197 controls were completely interviewed by public health nurses about cooking methods, ventilation, and other potential risk factors. Women who cooked at home in a kitchen (n=269) without the presence of a fume extractor at least once a week between the ages of 20 and 40 had a 2.29 times higher risk [95% confidence interval (CI)=1.08-4.87] of developing cervical intraepithelial neoplasm than those who did not cook once a week in such a kitchen during the same age span, after adjusting for other potential confounders. This finding was further strengthened by the finding that women who did not use the fume extractors had a 2.47 times higher risk (95% CI=1.15-5.32) of developing cervical intraepithelial neoplasm than women who cooked in kitchens with fume extractors that were always switched on while cooking. We also found a joint protective effect of fume extractor use among women older than 40 years (n=202) if they used the extractors during both age spans of their lives, ages 20-40 and >40 years. Comparing our findings on women more than 40 years old who used fume extractors during

HIV-positive MSM's knowledge of HPV and anal cancer self-sampling: A scoping review.

Science.gov (United States)

Poon, M K L; Wong, J P H; Li, A T W; Manuba, M; Bisignano, A; Owino, M; Vahabi, M

2018-02-01

Human papillomavirus (hpv) infection is the cause of anal squamous cell cancer (ascc) in 80% of cases. Available research has also shown high prevalence of anal hpv infection among men who have sex with men (msm). However, hpv vaccination is low among msm in Canada. In light of this information, we conducted a scoping review with the aim of exploring (1) the knowledge of hpv and anal cancer among hiv-positive msm and (2) the acceptability of hpv and anal cancer self-sampling in this population. In conducting the review, we searched five electronic databases for peer-reviewed articles and abstracts published in English, between 2007 and 2017. A total of 803 articles were retrieved; after accounting for duplicates ( n= 40) and unmet criteria ( n= 754), a total of 794 articles were excluded. A final total of nine articles were used in this review. Results of this review show that hiv-positive msm have limited knowledge regarding the risks of anal cancer associated with hiv and hpv coinfection. Furthermore, there is limited research on hpv and anal cancer self-sampling in this population. However, the review of available studies suggested that hiv-positive msm were open to anal cancer self-sampling. It also identified potential barriers to self-sampling. In conclusion, we provide suggestions and future directions for policy-makers and educators to develop inclusive and accessible strategies to reach hiv-positive msm regarding anal cancer education and self-screening.

Grade Crossing Protection in High-Speed, High-Density, Passenger-Service Rail Corridors

Science.gov (United States)

1973-01-01

The report is a preliminary examination of special aspects of grade crossing protection for operation of high-speed passenger trains in rail corridors for which complete grade separation is not possible. Overall system needs and constraints are indic...

Classifying low-grade and high-grade bladder cancer using label-free serum surface-enhanced Raman spectroscopy and support vector machine

Science.gov (United States)

Zhang, Yanjiao; Lai, Xiaoping; Zeng, Qiuyao; Li, Linfang; Lin, Lin; Li, Shaoxin; Liu, Zhiming; Su, Chengkang; Qi, Minni; Guo, Zhouyi

2018-03-01

This study aims to classify low-grade and high-grade bladder cancer (BC) patients using serum surface-enhanced Raman scattering (SERS) spectra and support vector machine (SVM) algorithms. Serum SERS spectra are acquired from 88 serum samples with silver nanoparticles as the SERS-active substrate. Diagnostic accuracies of 96.4% and 95.4% are obtained when differentiating the serum SERS spectra of all BC patients versus normal subjects and low-grade versus high-grade BC patients, respectively, with optimal SVM classifier models. This study demonstrates that the serum SERS technique combined with SVM has great potential to noninvasively detect and classify high-grade and low-grade BC patients.

Histopathologic observations of anorectal abnormalities in anal atresia.

Science.gov (United States)

Meier-Ruge, W A; Holschneider, A M

2000-01-01

Over the years from 1992 to 1997, 41 anorectal malformations (ARM) with histopathologic alterations were investigated to determine which morphologic abnormalities of the distal rectum accompany ARMs. Three other cases showed normal neuromuscular morphology; 9 further cases could not be evaluated owing to scanty biopsies. All resected specimens were caudocranially coiled and cryostat cut at -20 degrees C into serial sections, which were stained with a lactic dehydrogenase, succinic dehydrogenase, nitroxide synthase, and acetylcholinesterase reaction as well as hemalum and sirius red. Ten low, 15 intermediate, and 10 high forms of anal atresia (AA) were studied. In addition, six cloacal abnormalities were investigated. In 7 cases (17%) (5 intermediate, 2 low AAs), the characteristics of Hirschsprung's disease were observed. Oligoneuronal hypoganglionosis of the myenteric plexus proximal to the anal floor was diagnosed in 7 AAs (12%). In 10 children with high-type AA and resection of 1-5 cm distal rectum and in all cloacal anomalies (n = 6) defects of the muscularis propria were seen in the rectal-atresia sac. These defects were characterized by hypoplasia of the circular-muscle layer and/or the internal anal sphincter (IAS). Intestinal neuronal dysplasia of the submucous plexus was most frequently observed (12%) in high-type AA. A correlation between innervation anomalies or anomalies of the muscularis propria and the type of fistula could not be seen. In conclusion, all cases with high-type AA and cloacal anomalies were characterized by anomalies of the muscularis propria and/or IAS but this was not the case in intermediate and low-type AAs. Anomalies of the enteric nervous system were diagnosed in 60% of AAs.

Ettevõtte konkurentsieelis inimeste analüüsi abil / Mait Raava

Index Scriptorium Estoniae

Raava, Mait

2015-01-01

Ettevõtte töötajate analüüsimisest, analüütika tulemuste rakendamisest juhtivates ettevõttes. Viiest sambast, millel põhineb inimeste analüüsi edukas rakendamine, analüütika rakendamise etapid

The diagnostic and biological implications of laminin expression in serous tubal intraepithelial carcinoma.

Science.gov (United States)

Kuhn, Elisabetta; Kurman, Robert J; Soslow, Robert A; Han, Guangming; Sehdev, Ann Smith; Morin, Patrick J; Wang, Tian-Li; Shih, Ie-Ming

2012-12-01

There is compelling evidence to suggest that serous tubal intraepithelial carcinoma (STIC) is the likely primary site for the development of many pelvic high-grade serous carcinomas (HGSCs). Identifying molecules that are upregulated in STIC is important not only to provide biomarkers to assist in the diagnosis of STIC but also to elucidate our understanding of the pathogenesis of HGSC. In this study, we performed RNA sequencing to compare transcriptomes between HGSC and normal fallopian tube epithelium (FTE), and we identified LAMC1 encoding laminin γ1 as one of the preferentially upregulated genes associated with HGSC. Reverse transcription polymerase chain reaction further validated LAMC1 upregulation in HGSC as compared with normal FTE. Immunohistochemical analysis was performed on 32 cases of concurrent HGSC and STIC. The latter was diagnosed on the basis of morphology, TP53 mutations, and p53 and Ki-67 immunohistochemical patterns. Laminin γ1 immunostaining intensity was found to be significantly higher in STIC and HGSC compared with adjacent FTE in all cases (PSTIC and HGSC cells, laminin γ1 staining was diffuse and intense throughout the cytoplasm. More importantly, strong laminin γ1 staining was detected in all 13 STICs, which lacked p53 immunoreactivity because of null mutations. These findings suggest that the overexpression of laminin γ1 immunoreactivity and alteration of its staining pattern in STICs can serve as a useful tissue biomarker, especially for those STICs that are negative for p53 and have a low Ki-67 labeling index.

[Experience of diagnosis and treatment of exogenous high-grade fever].

Science.gov (United States)

Xiong, Xing-jiang; Wang, Jie

2011-06-01

There is a regular pattern in the diagnosis and treatment of exogenous high-grade fever, of which the key point is formula syndrome identification. Syndrome differentiation of the six channels is appropriate for not only exogenous cold but also various other conditions. The diagnosis and treatment of high-grade fever can also follow the law of syndrome differentiation of the six channels. The theory of epidemic febrile diseases stems from and elaborates on an understanding of exogenous febrile conditions, so many effective formulas used to treat epidemic febrile diseases also have great value in the treatment of high-grade fever. Deteriorated syndrome, which is central to this condition, is very commonly seen in cases of high-grade fever, the key therapeutic principle of which is established according to syndromes. Allowing analysis that does not rigidly adhere to either established modern diagnosis or traditional Chinese syndromes, prominent achievements could be made in treating high-grade fever by summarizing the regular presenting patterns in terms of the constitution and symptoms.

Anal HPV infection in HIV-positive men who have sex with men from China.

Directory of Open Access Journals (Sweden)

Lei Gao

Full Text Available BACKGROUND: Anal HPV infection, which contributes to the development of anal warts and anal cancer, is well known to be common among men who have sex with men (MSM, especially among those HIV positives. However, HIV and anal HPV co-infection among MSM has not been addressed in China. METHODS: A cross-sectional study was conducted in Beijing and Tianjin, China. Study participants were recruited using multiple methods with the collaboration of local volunteer organizations. Blood and anal swabs were collected for HIV-1 serological test and HPV genotyping. RESULTS: A total of 602 MSM were recruited and laboratory data were available for 578 of them (96.0%. HIV and anal HPV prevalence were 8.5% and 62.1%, respectively. And 48 MSM (8.3% were found to be co-infected. The HPV genotypes identified most frequently were HPV06 (19.6%, HPV16 (13.0%, HPV52 (8.5% and HPV11 (7.6%. Different modes of HPV genotypes distribution were observed with respect to HIV status. A strong dose-response relationship was found between HIV seropositivity and multiplicity of HPV genotypes (p<0.001, which is consistent with the observation that anal HPV infection was an independent predictor for HIV infection. CONCLUSIONS: A high prevalence of HIV and anal HPV co-infection was observed in the MSM community in Beijing and Tianjin, China. Anal HPV infection was found to be independently associated with increased HIV seropositivity, which suggests the application of HPV vaccine might be a potential strategy to reduce the acquisition of HIV infection though controlling the prevalence of HPV.

3-GROUP METAPHASE AS A MORPHOLOGIC CRITERION OF PROGRESSIVE CERVICAL INTRAEPITHELIAL NEOPLASIA

NARCIS (Netherlands)

MOURITS, MJE; PIETERS, WJLM; HOLLEMA, H; BURGER, MPM

OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were

Three-group metaphase as a morphologic criterion of progressive cervical intraepithelial neoplasia

NARCIS (Netherlands)

Mourits, M. J.; Pieters, W. J.; Hollema, H.; Burger, M. P.

1992-01-01

OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were

Unusual and unique distribution of anal high-risk human papillomavirus (HR-HPV among men who have sex with men living in the Central African Republic.

Directory of Open Access Journals (Sweden)

Ralph-Sydney Mboumba Bouassa

Full Text Available High-risk (HR human papillomavirus (HPV infection remains a great concern in relation to African men who have sex with men (MSM, especially those infected with HIV. The prevalence of HR-HPV and associated risk factors was estimated in a cross-sectional observational study covering MSM living in Bangui, Central African Republic.MSM receiving care at the Centre National de Référence des Infections Sexuellement Transmissibles et de la Thérapie Antirétrovirale, Bangui, were included. HIV serostatus and socio-demographic and behavioral characteristics were collected. HPV DNA was detected and genotyped on anal swabs using Anyplex™ II HPV28 test (Seegene, South Korea, and HSV DNA by in-house real-time PCR. Logistic regression analyses were used to determine risk factors associated with HPV outcomes.42 MSM (mean age, 23.2 years; range, 14-39 including 69.1% HIV-1-positive and 30.9% HIV-negative were prospectively enrolled. The prevalence of anal HPV was 69.1%, including 82.7% of HR-HPV which were multiple in 52.0%. The most prevalent genotypes were HPV-35, HPV-58, HPV-59 and HPV-31. While, HPV-16 and HPV-18 were present in a minority of samples. Multiple HR-HPV infection was more frequent in HIV-positive MSM (41.4% with 2.7 genotypes per anal samples than in HIV-negative (7.7% with 1.5 genotypes per anal samples. HPV types included in the prophylactic Gardasil-9® vaccine were detected in 68.9% of specimens and HPV-58 was the most frequently detected. MSM infected by HPV-16 and HPV-18 were all infected by HIV-1. Few anal swabs (11.9% contained HSV-2 DNA without relationship with HPV detection. Condomless receptive anal intercourse was the main risk factor to being infected with any type of HPV and condomless insertive anal intercourse was significantly less associated with HPV contamination than receptive anal intercourse (Odd ratio = 0.02.MSM in Bangui are at-risk of HIV and HR-HPV anal infections. The unusual distribution of HPV-35 as

Sonographic appearance of anal cushions of hemorrhoids.

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Aimaiti, Adilijiang; A Ba Bai Ke Re, Ma Mu Ti Jiang; Ibrahim, Irshat; Chen, Hui; Tuerdi, Maimaitituerxun; Mayinuer

2017-05-28

venous dilatation were obvious in the anal cushion of hemorhoidal tissues. After pathological results with arteriovenous fistulas were taken as the standard reference, we evaluated the compatibility between the two methods according to the Cohen's kappa co-efficiency calculation. The compatibility (Cohein kappa co-efficiency value) between "mosaic pattern" in the TPUS and arteriovenous fistula in pathology was very good (ĸ = 0.8939). When compared between different groups, TRUS presented the advantage that the mosaic pattern could be confirmed in more patients, especially for group A. There was a statistical difference when comparing group A with group B or C ( P hemorrhoids present with a pathologically abnormal cushion which usually appears as a "mosaic pattern" in sonography, which is in accord with an arteriovenous fistula in pathology. There are clearly different hemorrhoid structures shown by sonography. "Mosaic pattern" may be a parameter for surgical indication of grades III and IV hemorrhoids.

Avaliação da conduta conservadora na lesão intraepitelial cervical de alto grau Evaluación de la conducta conservadora en la lesión intraepitelial cervical de alto grado Evaluation of conservative management of high-grade cervical squamous intraepithelial lesion

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Nelson Shozo Uchimura

2012-06-01

transversal y retrospectivo realizado con 509 mujeres (15-76 años atendidas en el período de 1996 a 2006, con colpocitología oncótica alterada, en un servicio público de referencia en Maringá, Sur de Brasil. Los datos fueron colectados de los prontuarios médicos y se estudiaron las variables diagnóstico definitivo, tipos de tratamiento, ocurrencia de la lesión y reincidencias y se analizaron por medio de pruebas de asociación de chi-cuadrado de Pearson y exacto de Fisher. RESULTADOS: La lesión intraepitelial cervical de alto grado ocurrió en 168 casos; de estos, 31 mujeres se sometieron a la amputación cónica, 104 a cirugías de alta frecuencia, nueve a histerectomías y 24 recibieron conducta conservadora. Entre las mujeres con lesión de alto grado y tratadas de forma conservadora, ocho (33,3% reincidieron, mientras que de las sometidas a la conducta no conservadora, diez (6,9% reincidieron, siendo esta diferencia estadísticamente significativa (p=0,0009, RP=4,8 (IC95% 2,11;10,93. En aquellas que hicieron seguimiento clínico-citológico, tres (30,0% y, entre las cauterizadas, cinco (35,7% reincidieron en el plazo de tres años, sin diferencia significativa (p=0,5611. La reincidencia por debajo y por encima de los 30 años ocurrió, respectivamente, en siete (13,8% y 11 (12,2% mujeres (p=0,9955. CONCLUSIONES: La edad de la mujer no influencia el pronóstico de la reincidencia. El tratamiento conservador debe ser indicado como conducta de excepción, dada la alta tasa de reincidencia, y el seguimiento debe ser riguroso, con acompañamiento citológico y colposcópico por inclusive tres años, período en el que ocurre la mayoría de las reincidencias.OBJECTIVE: To assess the association between conservative management of high-grade cervical squamous intraepithelial lesions and recurrence rates and age groups. METHODS: Cross-sectional, retrospective, analytical observational study of 509 women (aged 15 to 76 with abnormal Pap smears attending a public reference

Nocturnal faecal soiling and anal masturbation.

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Clark, A F; Tayler, P J; Bhate, S R

1990-01-01

Two cases of late onset faecal soiling as a result of anal masturbation in children who were neither mentally handicapped nor psychotic were studied. The role of soiling in aiding the young person and his family to avoid separating and maturing is highlighted. We suggest that the association of anal masturbation and resistant nocturnal soiling may be unrecognised. PMID:2270946

Studies on high grade cerebral gliomas

International Nuclear Information System (INIS)

Bleehen, N.M.

1990-01-01

A brief review of attempts in the United Kingdom to improve the results of treatment of high grade (grade 3, 4) supra-tentorial astrocytomas is presented. The radiosensitizer misonidazole failed to improve the results of post-surgical radiotherapy, however, multivariate analysis of data from these patients has provided a prognostic index of use in defining good and poor prognosis patients. An overview study of adjuvant nitrosourea therapy trials has shown a small significant advantage for the chemotherapy. A study of chemosensitization by benznidazole of CCNU treatment of patients in relapse failed to demonstrate any effect. 13 references

High-grade surface osteosarcoma of the hand

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Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe [Nagasaki University Hospital, Department of Pathology, Nagasaki (Japan); Kumagai, Kenji; Shindo, Hiroyuki [Nagasaki University Graduate School of Biomedical Sciences, Department of Orthopedic Surgery, Nagasaki (Japan); Uetani, Masataka [Nagasaki University Graduate School of Biomedical Sciences, Department of Radiology and Radiation Biology, Nagasaki (Japan); Ishida, Tsuyoshi [National Center of Neurology and Psychiatry, Department of Pathology and Laboratory Medicine, Kohnodai Hospital, Chiba (Japan); Tokyo Medical and Dental University, Department of Molecular Bone and Cartilage Pathology, Hard Tissue Genome Research Center, Tokyo (Japan)

2007-09-15

A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis. (orig.)

High-grade surface osteosarcoma of the hand

International Nuclear Information System (INIS)

Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe; Kumagai, Kenji; Shindo, Hiroyuki; Uetani, Masataka; Ishida, Tsuyoshi

2007-01-01

A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis. (orig.)

Vascularized anal autotransplantation model in rats: preliminary report.

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Araki, J; Mihara, M; Narushima, M; Iida, T; Sato, T; Koshima, I

2011-11-01

Ostomy has served as an effective surgery for various anorectal disfunctions. However, it must also be noted that those patients suffered greatly from stresses caused by their stoma. Many alternative therapies have been developed, but none have solved this critical issue. Meanwhile, due to the improvements in operative methods and immunosuppressive therapy, allotranplantation has gained great popularity in recent years. Therefore, we began development of an anal transplantation model. The operation was performed in six adult Wistar rats that were divided into two groups. Group 1 underwent vascular anastomoses, while group 2 did not Group 1 grafts survived, fully recovering anal function. However, many of the group 2 grafts did not survive; those that did survive showed major defects in their anus, never recovering anal function. We succeeded in establishing the rat anal transplantation model utilizing super-microsurgery. While research in anal transplantation was behind compared to that in other fields, we hope that this model will bring significant possibilities for the future. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular biological factors in the diagnosis of cervical intraepithelial neoplasias

Directory of Open Access Journals (Sweden)

Yu. N. Ponomareva

2010-01-01

Full Text Available The authors have made a complex analysis of the molecular biological factors associated with cervical intraepithelial neoplasia. They have revealed that infection by oncogenic human papillomavirus types is associated with suppressed apoptosis and enhanced cellular proliferative activity, which can be effectively used in the diagnosis and prediction of cervical neoplasias to optimize management tac- tics and to improve the results of treatment.

High-grade renal injuries are often isolated in sports-related trauma

OpenAIRE

Patel, Darshan P.; Redshaw, Jeffrey D.; Breyer, Benjamin N.; Smith, Thomas G.; Erickson, Bradley A.; Majercik, Sarah D.; Gaither, Thomas W.; Craig, James R.; Gardner, Scott; Presson, Angela P.; Zhang, Chong; Hotaling, James M.; Brant, William O.; Myers, Jeremy B.

2015-01-01

© 2015 Elsevier Ltd. All rights reserved. Introduction: Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods: We identified patients with AAST grades III...

Complications of nonoperative management of high-grade blunt hepatic injuries.

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Kozar, Rosemary A; Moore, John B; Niles, Sarah E; Holcomb, John B; Moore, Ernest E; Cothren, C Clay; Hartwell, Elizabeth; Moore, Frederick A

2005-11-01

Nonoperative management of blunt hepatic injuries is highly successful. Complications associated with high-grade injuries, however, have not been well characterized. The purpose of the present study was therefore to define hepatic-related complications and associated treatment modalities in patients undergoing nonoperative management of high-grade blunt hepatic injuries. Three hundred thirty-seven patients from two regional Level I trauma centers with grade 3 to 5 blunt hepatic injuries during a 40-month period were reviewed. Complications and treatment of hepatic-related complications in patients not requiring laparotomy in the first 24 hours were identified. Of 337 patients with a grade 3 to 5 injury, 230 (68%) were managed nonoperatively. There were 37 hepatic-related complications in 25 patients (11%); 63% (5 of 8) of patients with grade 5 injuries developed complications, 21% (19 of 92) of patients with grade 4 injuries, but only 1% (1 of 130) of patients with grade 3 injuries. Complications included bleeding in 13 patients managed by angioembolization (n = 12) and laparotomy (n = 1), liver abscesses in 2 patients managed with computed tomography-guided drainage (n = 2) and subsequent laparotomy (n = 1). In one patient with bleeding, hepatic necrosis followed surgical ligation of the right hepatic artery and required delayed hepatic lobectomy. Sixteen biliary complications were managed with endoscopic retrograde cholangiopancreatography and stenting (n = 7), drainage (n = 5), and laparoscopy (n = 4). Three patients had suspected abdominal sepsis and underwent a negative laparotomy, whereas an additional three patients underwent laparotomy for abdominal compartment syndrome. Nonoperative management of high-grade liver injuries can be safely accomplished. Mortality is low; however, complications in grade 4 and 5 injuries should be anticipated and may require a combination of operative and nonoperative management strategies.

Experience in cervix intraepithelial neoplasia and the in situ carcinoma with radiosurgery

International Nuclear Information System (INIS)

Fajardo Tornes, Yarine; Lau Serrano, Dalgis; Perez Ramirez Fernando

2010-01-01

To expose the results from a longitudinal, prospective and descriptive study conducted in 1 437 patients diagnosed with cervical intraepithelial neoplasm (CIN) and in situ carcinoma (ISC) treated by radiosurgery in the neck pathology consultation of the 'Carlos Manuel de Cespedes' University Provincial Hospital during 2004-2009

Prevalência das lesões intra-epiteliais de alto grau em pacientes com citologia com diagnóstico persistente de ASCUS Prevalence of high-grade squamous intraepithelial lesions in patients with persistent cytological diagnosis of ASCUS

Directory of Open Access Journals (Sweden)

Fernanda Rangel da Veiga

2006-02-01

ASCUS é de cerca de 12%. Não foi possível evidenciar maior probabilidade de LIAG/câncer em qualquer das faixas etárias analisadas, porém este resultado pode ter sido limitado pelo pequeno tamanho amostral.PURPOSE: to determine the prevalence of high-grade squamous intraepithelial lesions (HSIL and cancer in women with cytological diagnosis of persistent ASCUS (atypical squamous cells of undetermined significance for 6 months in the last 7 years. We also assessed if age could be a predictive factor for presence of HSIL/cancer in this group. METHODS: we included 215 cases of non-pregnant and HIV-seronegative women with cytological diagnosis of persistent ASCUS (unespecific with at least 6 months of interval between smears. This cytological diagnosis was compared to histological diagnosis obtained by biopsy (large loop excision of the transformation zone or cone biopsies, and considered negative when colposcopy was satisfactory without lesions or, when unsatisfactory, no lesion was detected after at least one cytological and colposcopic follow-up. RESULTS: among the 215 cases, 49.3% had negative results (CI 95%: 42.6-55.9. The prevalence of histological confirmed low-grade squamous intraepithelial lesion was 38.6% (CI 95%: 32.1- 45.1 and HSIL was 10.7% (CI 95%: 6.5-14.8. Cases of cancer were found in 1.4% of patients (CI 95%: 0-2.9. We could not find a significant difference between the prevalence of HSIL/cancer according to age group using the cutoff point of 35 years. CONCLUSION: HSIL/cancer prevalence observed in this study has shown the risk of finding this kind of lesions in about 12% of women assisted in our public health system with two cytological diagnosis of ASCUS. A higher probability of HSIL/cancer in the different age groups was not found but this result was limited by our small sample size.

Retrospective study of the influence of HPV persistence on outcomes among women with high-risk HPV infections and negative cytology.

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Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Martinelli, Fabio; Signorelli, Mauro; Leone Roberti Maggiore, Umberto; Chiappa, Valentina; Scaffa, Cono; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

2017-07-01

To evaluate the outcomes of women diagnosed with high-risk HPV without cytology evidence of cervical dysplasia. The present retrospective observational study enrolled consecutive women aged at least 18 years diagnosed with high-risk HPV types with negative cytology results at the National Cancer Institute, Milan, Italy, between January 1, 2005, and December 31, 2015. The development of cervical intraepithelial neoplasia (CIN) was assessed. There were 212 patients with high-risk HPV infections with negative cytology included in the analysis. After a mean ± SD follow-up period of 48 ± 33 months, 65 (30.7%) and 26 (12.3%) patients had developed cytologic or histologic cervical dysplasia (low-grade squamous intraepithelial lesion [LSIL]/CIN1+) and high-grade cervical dysplasia (CIN2+), respectively. No patients had invasive cancer. No correlations were observed between type-specific HPV infections and LSIL/CIN1+ and CIN2+. HPV persistence correlated with both LSIL/CIN1+ (P<0.001) and CIN2+ (P<0.001) in univariate analyses; a 6-month increase in HPV persistence was associated with increased risk of developing LSIL/CIN1+ (P=0.010) and CIN2+ (P=0.012) in multivariate analyses. Regardless of cytology findings, patients diagnosed with high-risk HPV types should receive strict colposcopy follow-up, particularly with persistent HPV infections. Further prospective studies are needed to defined optimal surveillance strategies for these patients. © 2017 International Federation of Gynecology and Obstetrics.

Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube.

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Yang, Junzheng; Zhou, Yilan; Ng, Shu-Kay; Huang, Kuan-Chun; Ni, Xiaoyan; Choi, Pui-Wah; Hasselblatt, Kathleen; Muto, Michael G; Welch, William R; Berkowitz, Ross S; Ng, Shu-Wing

2017-06-17

Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors. RNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors. Ovarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection. The activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade

Early effect of external beam radiation therapy on the anal sphincter: A study using anal manometry and transrectal ultrasound

International Nuclear Information System (INIS)

Birnbaum, E.H.; Dreznik, Z.; Myerson, R.J.; Lacey, D.L.; Fry, R.D.; Kodner, I.J.; Fleshman, J.W.

1992-01-01

The early of pelvic irradiation on the anal sphincter has not been previously investigated. This study prospectively evaluated the acute effect of preoperative radiation on anal function. Twenty patients with rectal carcinoma received 4,500 cGy of preoperative external beam radiation. The field of radiation included the sphincter in 10 patients and was delivered above the anorectal ring in 10 patients. Anal manometry and transrectal ultrasound were performed before and four weeks after radiotherapy. No significant difference in mean maximal squeeze or resting pressure was found after radiation therapy. An increase in mean minimal sensory threshold was significant. Histologic examination revealed minimal radiation changes at the distal margin in 8 of 10 patients who underwent low anterior resection and in 1 of 3 patients who underwent abdominoperineal resection. The authors conclude that preoperative radiation therapy has minimal immediate effect on the anal sphincter and is not a major contributing factor to postoperative incontinence in patients after sphincter-saving operations for rectal cancer

De chirurgische betekenis van de inwendige kringspier van het anale kanaal : een klinisch en manometrisch onderzoek

NARCIS (Netherlands)

W.R. Schouten (Ruud)

1990-01-01

textabstractThe high pressure zone within the anal canal is largely due to the activity of the internal anal sphincter and provides an effective barrier against rectal pressure. The continuous contraction of the internal sphincter also has a congesting effect on the vascular cushions, thereby

Diagnostic imaging features of normal anal sacs in dogs and cats.

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Jung, Yechan; Jeong, Eunseok; Park, Sangjun; Jeong, Jimo; Choi, Ul Soo; Kim, Min-Su; Kim, Namsoo; Lee, Kichang

2016-09-30

This study was conducted to provide normal reference features for canine and feline anal sacs using ultrasound, low-field magnetic resonance imaging (MRI) and radiograph contrast as diagnostic imaging tools. A total of ten clinically normal beagle dogs and eight clinically normally cats were included. General radiography with contrast, ultrasonography and low-field MRI scans were performed. The visualization of anal sacs, which are located at distinct sites in dogs and cats, is possible with a contrast study on radiography. Most surfaces of the anal sacs tissue, occasionally appearing as a hyperechoic thin line, were surrounded by the hypoechoic external sphincter muscle on ultrasonography. The normal anal sac contents of dogs and cats had variable echogenicity. Signals of anal sac contents on low-field MRI varied in cats and dogs, and contrast medium using T1-weighted images enhanced the anal sac walls more obviously than that on ultrasonography. In conclusion, this study provides the normal features of anal sacs from dogs and cats on diagnostic imaging. Further studies including anal sac evaluation are expected to investigate disease conditions.

Anal metastasis originating from colorectal cancer: Report of two cases

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Min; Lim, Joon Seok; Choi, Jin Young; Park, Mi Suk; Kim, Myeong Jin [Dept. of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Taek; Kim, Ho Guen [Dept. of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2016-12-15

Anal metastasis from colorectal cancer rarely occurs, but it severely impairs the patient's quality of life, often requiring wide resection including the anal sphincter with permanent colostomy. This lesion can be misdiagnosed as a perianal fistula or an abscess, and it can be overlooked at the time of surgery because it is not included in the routine surgical extent of low anterior resection. We report two rare cases of anal metastasis from colorectal cancer. In both cases, perianal nodules with an internal solid portion were detected on preoperative rectal magnetic resonance imaging and additional local excisions of the anal lesions were performed during the process of treatment. Anal metastasis was pathologically confirmed by histology and immunohistochemical staining.

Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal

International Nuclear Information System (INIS)

Peddada, Anuj V.; Smith, Damon E.; Rao, Aroor R.; Frost, Daniel B.; Kagan, A. Robert

1997-01-01

Purpose: To determine the efficacy and tolerance of a standardized protocol of chemotherapy and low-dose radiotherapy in the treatment of anal cancer in human immunodeficiency virus (HIV)-infected patients. Methods and Materials: Between 1987 and 1995, eight HIV-positive patients with squamous cell carcinoma of the anal canal, four of whom had acquired immunodeficiency syndrome (AIDS), received therapy at the Kaiser Permanente Medical Center. All patients were treated using a combined modality approach consisting of lowdose radiotherapy (30 Gy in 15 fractions delivered 5 days/week), and chemotherapy [1000 mg/m 2 of 5-fluorouracil (5-FU) delivered on days 1-4 and 29-32 as a continuous infusion over 96 h, and 10 mg/m 2 of mitomycin C delivered as a bolus injection on day 1]. Patients have been followed from 4 to 81 months (mean 41, median 38). Results: All eight patients completed the therapy with minor variations to the protocol, and all have attained a clinical complete response. Four patients are alive and free of disease, and four died as a result of complications of AIDS, but remained free of anal carcinoma. There were no mortalities from the protocol and the morbidity was acceptable. Only one patient each was noted to have Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 4 hematologic and gastrointestinal acute toxicity, and no Grade 4 skin toxicity was noted. Conclusion: This combined therapy is effective for HIV-infected patients and appears to be tolerable with acceptable toxicities. It is best applied to patients who are HIV positive, or who have AIDS without concurrent major opportunistic infections. This approach is reasonable and affords patients a reasonably good chance at sphincter preservation by avoiding abdominoperineal resection. The optimal therapy for HIV-positive patients with advanced AIDS remains less well defined

Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

International Nuclear Information System (INIS)

Olsen, Jeffrey R.; Moughan, Jennifer; Myerson, Robert; Abitbol, Andre; Doncals, Desiree E.; Johnson, Douglas; Schefter, Tracey E.; Chen, Yuhchyau; Fisher, Barbara; Michalski, Jeff; Narayan, Samir; Chang, Albert; Crane, Christopher H.; Kachnic, Lisa

2017-01-01

Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P 4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.

Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India.

Science.gov (United States)

Hernandez, Alexandra L; Karthik, Rajiv; Sivasubramanian, Murugesan; Raghavendran, Anantharam; Gnanamony, Manu; Lensing, Shelly; Lee, Jeannette Y; Kannangai, Rajesh; Abraham, Priya; Mathai, Dilip; Palefsky, Joel M

2016-04-01

India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)]. Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions.

Avaliação manométrica anal de crianças com encoprese Anal manometric evaluation of children with encopresis

Directory of Open Access Journals (Sweden)

Maria Auxiliadora Prolungatti Cesar

2010-12-01

Full Text Available INTRODUÇÃO: A constipação crônica é doença comum na infância, ocorrendo em 5 a 10% dos pacientes pediátricos, considerada a segunda maior causa de procura nos consultórios de pediatria, sendo a encoprese decorrente de constipação grave associada à impactação fecal no reto. Dentre os exames diagnósticos, a manometria anal é utilizada para a avaliação de pacientes com distúrbios funcionais, como a constipação intestinal e a incontinência fecal, em alguns serviços para a avaliação de pacientes com encoprese, pois pode trazer informações sobre o mecanismo evacuatório e possíveis lesões esfincterianas anais. OBJETIVO: Verificar alterações manométricas em pacientes com encoprese. MÉTODOS: Foi realizado estudo de 40 manometrias anais de crianças constipadas com encoprese (G1 e 12 crianças constipados sem encoprese (G2. Foram obtidos os seguintes dados: pressões de repouso, contração e evacuação do canal anal e ampola retal, ponto de maior pressão, reflexo inibitório anal e sensibilidade retal. As manometrias foram realizadas com o aparelho Alacer de perfusão com 8 canais. RESULTADOS: Não foram encontradas diferenças nas pressões de repouso, contração e evacuação do canal anal entre os grupos. Chamou-nos a atenção a ausência de necessidade de maior volume retal para desencadear o reflexo inibitório anal. Não houve diferença da incidência de anismus entre os dois grupos, demonstrando que não se trata de fator importante na manutenção da encoprese, mas sim da constipação. CONCLUSÃO: Não houve necessidade de maior volume para desencadear o reflexo inibitório anal. O anismus não foi diferente entre os dois grupos, não sendo importante na manutenção da encoprese.INTRODUCTION: Chronic constipation is a common childhood disorder that affects 5 to 10% of pediatric patients, being the second most common cause for seeking medical help, with the encopresis arising out of severe constipation

Underground Milling of High-Grade Uranium Ore

Energy Technology Data Exchange (ETDEWEB)

Edwards, C., E-mail: chuck.edwards@amec.com [AMEC Americas Limited, Saskatoon, Saskatchewan (Canada)

2014-05-15

There are many safety and technical issues involved in the mining and progressing of high grade uranium ores such as those exploited in Northern Canada at present. With more of this type of mine due to commence production in the near future, operators have been looking at ways to better manage the situation. The paper describes underground milling of high-grade uranium ore as a means of optimising production costs and managing safety issues. In addition the paper presents some examples of possible process flowsheets and plant layouts that could be applicable to such operations. Finally an assessment of potential benefits from underground milling from a variety of viewpoints is provided. (author)

Uptake and Predictors of Anal Cancer Screening in Men Who Have Sex With Men

Science.gov (United States)

D'Souza, Gypsyamber; Rajan, Shirani D.; Bhatia, Rohini; Cranston, Ross D.; Plankey, Michael W.; Silvestre, Anthony; Ostrow, David G.; Wiley, Dorothy; Shah, Nisha; Brewer, Noel T.

2013-01-01

Objectives. We investigated attitudes about and acceptance of anal Papanicolaou (Pap) screening among men who have sex with men (MSM). Methods. Free anal Pap screening (cytology) was offered to 1742 MSM in the Multicenter AIDS Cohort Study, who reported history of, attitudes about, and experience with screening. We explored predictors of declining screening with multivariate logistic regression. Results. A history of anal Pap screening was uncommon among non–HIV-infected MSM, but more common among HIV-infected MSM (10% vs 39%; P < .001). Most participants expressed moderate or strong interest in screening (86%), no anxiety about screening (66%), and a strong belief in the utility of screening (65%). Acceptance of screening during this study was high (85%) across all 4 US sites. Among those screened, most reported it was “not a big deal” or “not as bad as expected,” and 3% reported that it was “scary.” Declining to have screening was associated with Black race, anxiety about screening, and low interest, but not age or HIV status. Conclusions. This study demonstrated high acceptance of anal Pap screening among both HIV-infected and non–HIV-infected MSM across 4 US sites. PMID:23865658

Treatment of cervical intraepithelial neoplasia in Denmark 1991 to 2007

DEFF Research Database (Denmark)

Barken, Sidsel Svennekjær

2010-01-01

Abstract: Objectives: The number of invasive cervical cancers peaked in Denmark in 1966 with 963 cases. Cervical cancer is prevented by treatment of screen-detected cervical intraepithelial neoplasia (CIN). We assessed the trend in CIN treatments in Denmark. Material and Methods: From highly...... the data using the unique Danish identification numbers, and excluded all duplicate registrations. We excluded all destructive therapies and hysterectomies for which no CIN or cervical cancer diagnosis was found in the period from 3 months before to 1 month after the treatment date. We age......-standardized the number of cervical treatments using Danish women in 2007 as standard population. Results: The preliminary analysis shows that the number of treatments increased from about 6,000 in 1991 to about 8,200 in 2007, most noticeably due to an increase of about 2,600 in the number of conisations (Figure 1...

Variantes de lesões intra-epiteliais escamosas: relato de quatro casos Variants of intraepithelial squamous lesions: report of four cases

Directory of Open Access Journals (Sweden)

Álvaro P. Pinto

2005-04-01

Full Text Available Entre a rotina de biópsias e produtos cirúrgicos provenientes do colo uterino, um número significativo de lesões intra-epiteliais escamosas (LIE pode causar dificuldade quanto a caracterização e graduação histológica. Tais lesões têm sido identificadas e descritas isoladamente por artigos científicos como variantes histológicas de LIE cervicais. São elas a metaplasia papilar imatura atípica (MPIA e as variantes de neoplasia intra-epitelial cervical graus II/III: queratinizante, com padrão metaplásico imaturo de crescimento e escamomucinosa. Neste artigo são exemplificados quatro casos representativos das entidades citadas acima, provenientes das rotinas do Programa de Prevenção do Câncer Ginecológico do Estado do Paraná e de um laboratório privado especializado em patologia ginecológica de Curitiba, o Laboratório de Citopatologia e Anatomia Patológica Annalab. Os principais critérios diagnósticos são descritos, assim como a correlação citológica e molecular relacionada à presença e à localização do ácido nucleico viral (papilomavírus humano [HPV] nas lesões.In routine basis, among biopsies and surgical specimens derived from uterine cervix, a significant number of squamous intraepithelial lesions (SIL may be difficult to diagnose and grade. Some of these lesions were identified, isolated and reported in scientific articles as histological variants of SIL. They are: metaplastic papillary immature atypia (MPIA and the following grade II/III cervical intraepithelial neoplasia variants: keratinized, immature metaplastic-like proliferation and mucin-producing. In this article four cases representative of these variants are described. They were retrieved from the routines of a large scale gynecological cancer screening program and a private laboratory specialized on gynecological pathology, both from Paraná State, Brazil. The main histological criteria for diagnosis are described, as well cytological and

Prevalence of intraepithelial lesion in cervical screening cytology in a First-level Care Unit

Science.gov (United States)

Solís, José Gabriel; Briones-Torres, Tomás Iván

2018-01-01

Cervical cancer represents the second leading cause of malignant neoplasm mortality in women globally. Cervical cytology is the most important screening study. It is therefore of interest to know the prevalence of cytological alterations in the Mexican population. In this study the objective was to calculate the prevalence of intraepithelial lesion in cervical screening cytology. An observational, descriptive and cross-sectional study was developed; the sample was 379 patients from 21 to 64 years of age; we included patients who underwent cervical screening cytology registered in the Detección Oportuna de Cáncer Cervicouterino (DOC-CACU) program database. A descriptive analysis of the data was performed. A prevalence of intraepithelial lesion of 4.49% was found. The 3.17% corresponded to LIEBG and 1.32% to LIEAG. No reports of invasive carcinoma were found. Of these patients, 64.71% corresponded to the age group from 41 to 60 years. 52.94% had had their last cytology in the previous 3 years or more and 35.29% were in postmenopause. A prevalence consistent with what was described in the literature was found. More than half of the affected patients had their last cytology in the previous 3 or more years and corresponded to the age group from 41 to 60 years. A high proportion of patients were in postmenopause.

High grade magnesium from waste bittern

International Nuclear Information System (INIS)

El-Yamani, I.S.; Farah, M.Y.; Isaac, S.L.

1979-01-01

The production of high grade magnesia for nuclear purposes from sea water by use of both aqueous and gaseous ammonia has been described. The effect of precipitating conditions on the settling rate and magnesium recovery, was thoroughly examined. Ammonia gas approach was recommended and justified

Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

Directory of Open Access Journals (Sweden)

Devic Ana

2015-12-01

Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.

Sotsiaalvõrgustike analüüs / Innar Liiv

Index Scriptorium Estoniae

Liiv, Innar, 1982-

2005-01-01

Sotsiaalvõrgustike analüüs (social network analys - SNA) on tehnikate, meetodite ning vahendite kogum, mis aitab avastada mustreid sotsiaalsetes struktuurides. Analüüsi kasutamisest energeetikaettevõtte Enron ja kohalike ettevõtete võrgustike näitel. Skeemid

Anal Cancer Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Anal cancer is often curable with treatment. Major prognostic factors are site, size, and nodal status. Treatments include radiation therapy, chemotherapy, and surgery. Get detailed information for anal cancer risk factors, classification, staging, prognosis, and treatment in this summary for clinicians.

KRAS and BRAF mutations in anal carcinoma

DEFF Research Database (Denmark)

Serup-Hansen, Eva; Linnemann, Dorte; Høgdall, Estrid

2015-01-01

the frequency and the prognostic value of KRAS and BRAF mutations in a large cohort of patients with anal cancer. One hundred and ninety-three patients with T1-4N0-3M0-1 anal carcinoma were included in the study. Patients were treated with curative (92%) or palliative intent (8%) between January 2000...

Recent Advances in the Pharmacotherapy of Chronic Anal Fissure: An Update

Directory of Open Access Journals (Sweden)

Bikash Medhi

2008-07-01

Full Text Available Surgical sphincterotomy reduces anal tone and sphincter spasm and promotes ulcer healing. Because the surgery is associated with the side effect of faecal incontinence, pharmacological agents to treat chronic anal fissure have been explored recently. Glyceryl trinitrate (GTN ointment (0.2% has an efficacy of up to 68% in healing chronic anal fissure, but it is associated with headache as the major and most common side effect. Though botulinum toxin injected into the anal sphincter healed over 80% of chronic anal fis-sures, it is more invasive and expensive than GTN therapy. Diltiazem ointment achieved healing of chronic anal fissure comparable to 0.2% GTN ointment but was associated with fewer side effects. Other drugs that have been tried are lidocaine, the alpha-adrenergic antagonist indoramin, and the potassium channel opener minoxidil.

Mining the high grade McArthur River uranium deposit

International Nuclear Information System (INIS)

Jamieson, B.W.

2002-01-01

The McArthur River deposit, discovered in 1988, is recognized as the world's largest, highest grade uranium deposit, with current mineable reserves containing 255 million lb U 3 O 8 at an average grade of 17.33% U 3 O 8 . In addition the project has resources of 228 million pounds U 3 O 8 averaging 12.02% U 3 O 8 . Mining this high-grade ore body presents serious challenges in controlling radiation and in dealing with high water pressures. Experience from the underground exploration programme has provided the information needed to plan the safe mining of the massive Pelite ore zone, which represents the most significant source of ore discovered during the underground drilling programme, with 220 million pounds of U 3 O 8 at an average grade in excess of 17%. Non-entry mining will be used in the high-grade ore zones. Raise boring will be the primary method to safely extract the ore, with all underground development in waste rock to provide radiation shielding. Water will be controlled by grouting and perimeter freezing. The ore cuttings from the raise boring will be ground underground and pumped to surface as slurry, at an average daily production of 150 tonnes. The slurry will be transported to the Key Lake mill and diluted to 4% before processing. The annual production is projected to be 18 million lb U 3 O 8 . The paper focuses on the activities undertaken since discovery, including the initiation of the raise bore mining method utilized to safely mine this high grade ore body. Radiation protection, environmental protection and worker health and safety are discussed in terms of both design and practical implementation. (author)

Clinical Application of F-18 FDG PET (PET/CT) in Colo-rectal and Anal Cancer

International Nuclear Information System (INIS)

Kim, Byung Il

2008-01-01

In the management of colo-retal and anal cancer, accurate staging, treatment evaluation, early detection of recurrence are main clinical problems. F-18 FDG PET (PET/CT) has been reported as useful in the management of colo-rectal and anal cancer because that PET has high diagnostic performance comparing to conventional studies. In case of liver metastases, for confirmation of no extrahepatic metastases, in case of high risk of metastasis, for avoiding unnecessary operation, PET (PET/CT) is expected more useful. In anal cancer, PET is expected useful in lymph node staging. For the early prediction of chemotherapy or radiation therapy effect PET has been reported as useful, also. In early detection of recurrence by PET, cost-benefit advantages has been suggested, also. PET/CT is expected to have higher diagnostic performance than PET alone

Symptom outcomes important to women with anal incontinence: a conceptual framework.

Science.gov (United States)

Sung, Vivian W; Rogers, Rebecca G; Bann, Carla M; Arya, Lily; Barber, Matthew D; Lowder, Jerry; Lukacz, Emily S; Markland, Alayne; Siddiqui, Nazema; Wilmot, Amanda; Meikle, Susan F

2014-05-01

To develop a framework that describes the most important symptom outcomes for anal incontinence treatment from the patient perspective. A conceptual framework was developed by the Pelvic Floor Disorders Network based on four semistructured focus groups and confirmed in two sets of 10 cognitive interviews including women with anal incontinence. We explored: 1) patient-preferred terminology for describing anal incontinence symptoms; 2) patient definitions of treatment "success"; 3) importance of symptoms and outcomes in the framework; and 4) conceptual gaps (defined as outcomes not previously identified as important). Sessions were conducted according to grounded theory transcribed, coded, and qualitatively and quantitatively analyzed to identify relevant themes. Content and face validity of the framework were further assessed using cognitive interviews. Thirty-four women participated in focus groups and 20 in cognitive interviews. Overall, 29 (54%) were aged 60 years or older, 42 (78%) were white, and 10 (19%) had a high school degree or less. Two overarching outcome themes were identified: "primary bowel leakage symptoms" and "ancillary bowel symptoms." Subdomains important in primary bowel leakage symptoms included leakage characteristics (symptom frequency, amount of leakage, symptom bother) and conditions when bowel leakage occurs (predictability, awareness, urgency). Subdomains important under ancillary bowel symptoms included emptying disorders (constipation, obstructed defecation, and wiping issues) and discomfort (pain, burning). New outcomes identified included predictability, awareness, wiping issues, and discomfort. Women with anal incontinence desire a wide range of symptom outcomes after treatment. These are captured in our conceptual framework, which can aid clinicians and researchers in assessing anal incontinence. LEVEL OF EVIEDENCE: II.

Using of thermoradiotherapy on treatment of cancerous growths of anal canal

International Nuclear Information System (INIS)

Timofeev, Yu.M.; Zikiryakhodjaev, D.Z.

1997-01-01

In this chapter of book authors investigated using of thermoradiotherapy on treatment of cancerous growths of anal canal, methods of using of thermoradiotherapy at morbid with anal cancer, methods of irradiation, the characteristic of clinical observations, using of thermoradiotherapy at treatment of epidermoid cancer of anal zone, using of thermoradiotherapy at treatment of non epithelial cancer of anal zone and using thermoradiotherapy at others types of cancerous growths

The impact of anaemia on treatment outcome in patients with squamous cell carcinoma of anal canal and anal margin

Directory of Open Access Journals (Sweden)

Oblak Irena

2016-03-01

Full Text Available Radiochemotherapy is the main treatment for patients with squamous cell carcinoma of the anal canal. Anaemia is reported to have adverse effect on survival in cancer patients. The aim of the study was to evaluate the influence of anaemia on radiochemotherapy treatment outcome in patients with squamous cell carcinoma of the anal canal.

Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α