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Sample records for intraepithelial neoplasia identification

  1. Anal intraepithelial neoplasia in HIV+ men

    NARCIS (Netherlands)

    Richel, O.

    2014-01-01

    In this thesis we investigated several aspects of anal intraepithelial neoplasia (AIN) in HIV+ men who have sex with men (MSM). This condition has gained clinical interest because of the impressive increase of the anal cancer incidence in HIV+ MSM since the introduction of combination antiretroviral

  2. 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.

  3. 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.

  4. 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.

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

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    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

  6. 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...

  7. 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...

  8. Lobular intraepithelial neoplasia arising within breast fibroadenoma

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    2013-01-01

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

  9. Molecular biological factors in the diagnosis of cervical intraepithelial neoplasias

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    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.

  10. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    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....

  11. Cold-knife and laser conization for cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    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...

  12. 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...

  13. 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.

  14. 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.

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

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

    2014-11-01

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

  16. 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

  17. 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

  18. Fractal dimension and image statistics of anal intraepithelial neoplasia

    International Nuclear Information System (INIS)

    Ahammer, H.; Kroepfl, J.M.; Hackl, Ch.; Sedivy, R.

    2011-01-01

    Research Highlights: → Human papillomaviruses cause anal intraepithelial neoplasia (AIN). → Digital image processing was carried out to classify the grades of AIN quantitatively. → The fractal dimension as well as grey value statistics was calculated. → Higher grades of AIN yielded higher values of the fractal dimension. → An automatic detection system is feasible. - Abstract: It is well known that human papillomaviruses (HPV) induce a variety of tumorous lesions of the skin. HPV-subtypes also cause premalignant lesions which are termed anal intraepithelial neoplasia (AIN). The clinical classification of AIN is of growing interest in clinical practice, due to increasing HPV infection rates throughout human population. The common classification approach is based on subjective inspections of histological slices of anal tissues with all the drawbacks of depending on the status and individual variances of the trained pathologists. Therefore, a nonlinear quantitative classification method including the calculation of the fractal dimension and first order as well as second order image statistical parameters was developed. The absolute values of these quantitative parameters reflected the distinct grades of AIN very well. The quantitative approach has the potential to decrease classification errors significantly and it could be used as a widely applied screening technique.

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

    DEFF Research Database (Denmark)

    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....

  20. Psychological effects of diagnosis and treatment of cervical intraepithelial neoplasia

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    Frederiksen, Maria Eiholm; Njor, Sisse; Lynge, Elsebeth

    2015-01-01

    BACKGROUND: Treatment of cervical intraepithelial neoplasia (CIN) is a common minor surgical procedure to prevent uterine cervical cancer. However, news of an abnormality detected at screening for cancer might cause the woman to worry. OBJECTIVES: To investigate the psychological consequences...... test results, but the impact decreased over time. In several but not all studies, CIN appeared to have similar psychological consequences to abnormal smears. No study showed a difference in psychological outcomes between CIN and cervical cancer diagnosis when these were measured some years after...... psychological outcomes in women with a histological diagnosis or treatment of CIN, and in women having an outcome other than CIN at cervical screening. DATA COLLECTION AND ANALYSIS: We abstracted the data using a pre-specified list of study characteristics and measured outcomes. For studies not reporting...

  1. 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.

  2. Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

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

    2008-05-01

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

  3. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

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    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.

  4. 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.

  5. 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.

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

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    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.

  7. Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

    Science.gov (United States)

    Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

    2013-01-01

    Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

  8. Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

    Science.gov (United States)

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

    1991-01-01

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

  9. DNA-Cytometry of Progressive and Regressive Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Antonius G. J. M. Hanselaar

    1998-01-01

    Full Text Available A retrospective analysis was performed on archival cervical smears from a group of 56 women with cervical intraepithelial neoplasia (CIN, who had received follow‐up by cytology only. Automated image cytometry of Feulgen‐stained DNA was used to determine the differences between progressive and regressive lesions. The first group of 30 smears was from women who had developed cancer after initial smears with dysplastic changes (progressive group. The second group of 26 smears with dysplastic changes had shown regression to normal (regressive group. The goal of the study was to determine if differences in cytometric features existed between the progressive and regressive groups. CIN categories I, II and III were represented in both groups, and measurements were pooled across diagnostic categories. Images of up to 700 intermediate cells were obtained from each slide, and cells were scanned exhaustively for the detection of diagnostic cells. Discriminant function analysis was performed for both intermediate and diagnostic cells. The most significant differences between the groups were found for diagnostic cells, with a cell classification accuracy of 82%. Intermediate cells could be classified with 60% accuracy. Cytometric features which afforded the best discrimination were characteristic of the chromatin organization in diagnostic cells (nuclear texture. Slide classification was performed by thresholding the number of cells which exhibited progression associated changes (PAC in chromatin configuration, with an accuracy of 93 and 73% for diagnostic and intermediate cells, respectively. These results indicate that regardless of the extent of nuclear atypia as reflected in the CIN category, features of chromatin organization can potentially be used to predict the malignant or progressive potential of CIN lesions.

  10. Identificação de tipos de papilomavirus e de outros fatores de risco para neoplasia intra-epitelial cervical Identification of papillomavirus types and other risk factors for cervical intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Terezinha Tenório da Silva

    2006-05-01

    infecção por HPV oncogênico, com os tipos 16, 18, 33, 35, 51, 52, 58 e 83. Dentre as portadoras de lesões de alto grau, houve predomínio de HPV-16 ou variante 16. Nas pacientes com colo morfologicamente normal, também foram identificados os tipos oncogênicos 51, 58 e variante 51.PURPOSE: to identify risk factors for cervical intraepithelial neoplasia (CIN and human papillomavirus (HPV types among women with CIN, and to compare with HPV types among patients with normal cervix. METHODS: a total of 228 patients were studied, of whom 132 with CIN (cases and 96 with normal cervix (controls. In the two groups consisting of women selected among outpatients attended in the same hospital, living near the place of the research, mean ages were similar (34.0±8.3 years and there was a predominance of married women. Possible risk factors for CIN were investigated with the application of a questionnaire surveying age, marital status, level of schooling, age at first coitus, number of pregnancies, number of sexual partners, method of used contraception, reference of previously sexually transmitted diseases (STDs and smoking habits, with a comparison between the studied groups. Samples were collected for oncologic colpocytology and HPV search through polymerase chain reaction (PCR, using MY09/MY11 primers; then colposcopic and histopathological examinations were performed. For statistical analysis of the association between risk factors and CIN, odds ratio with 95% confidence interval and chi2 and Fisher tests were used at a significance level of 0.05. The logistic regression method with the significance expressed by the p value with maximum likelihood was also applied. RESULTS: the following variables remained in the logistic regression model: HPV infection of high oncogenic risk (OR=12.32; CI 95%: 3.79-40.08, reference of previous STDs (OR=8.23; CI 95%: 2.82-24.04, early age at first coitus (OR=4.00; CI 95%: 1.70-9.39 and smoking habit (OR=3.94; CI 95%: 1.73-8.98. PCR was

  11. Increased burden of treatment of cervical intraepithelial neoplasia: Denmark 1991 to 2007

    DEFF Research Database (Denmark)

    Barken, Sidsel Svennekjær; Rebolj, M; Lynge, Elsebeth

    2011-01-01

    Introduction: Since the introduction of cytological screening in Denmark in the late 1960s, the incidence of cervical cancer decreased from 40 to 14 per 100,000 due to treatment of screen-detected cervical intraepithelial neoplasia (CIN). However, some overtreatment is inevitable and its side...... on conisations, destructive therapies, excisions, hysterectomies and cervical treatments NOS from: The Pathology, Hospital Discharge, Health Insurance and Danish Cancer Register, for all female Danish residents aged 15 to 84 between 1991 and 2007. After linking the data using the unique Danish identification...... numbers, we excluded all duplicates and all destructive therapies and hysterectomies for which no cervical diagnosis was found in the period around the treatment. The total number of treatments was age-standardized using the Danish female population in 2007 as the standard population. Results...

  12. 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.

  13. 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

  14. High-Resolution Anoscopy: Clinical Features of Anal Intraepithelial Neoplasia in HIV-positive Men

    NARCIS (Netherlands)

    Richel, Olivier; Hallensleben, Nora D. L.; Kreuter, Alexander; van Noesel, Carel J. M.; Prins, Jan M.; de Vries, Henry J. C.

    2013-01-01

    BACKGROUND: High-resolution anoscopy is increasingly advocated to screen HIV+ men who have sex with men for anal cancer and its precursor lesions, anal intraepithelial neoplasia. A systematic comparison between clinical features and the histopathology of suspect lesions is lacking. OBJECTIVE: This

  15. 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

  16. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Helmerhorst, Theo; Habbema, Dik

    2012-01-01

    To compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear test results with women with a normal primary smear test result....

  17. 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

  18. 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

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

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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

  2. Serous tubal intraepithelial neoplasia: the concept and its application.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    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...

  5. Characterization of a group of patients with cervical intraepithelial neoplasia diagnosed by diathermic loop biopsy

    International Nuclear Information System (INIS)

    Torriente Hernandez, Santa; Valdes Alvarez, Orlando; Villarreal Martinez, Aracelis; Lugo Sanchez, Ana

    2011-01-01

    A retrospective, longitudinal and descriptive study was conducted in 2 696 medical records corresponding to patients diagnosed with cervical intraepithelial neoplasia (CIN) and invasive cancer of cervix uteri (CCU) seen in the mother hospital of Guanabacoa municipality over above mentioned period. The information processing was from the data retrieval from medical records and biopsy control registry entering in a database in Microsoft Excel and the statistic processing using the SPSS package version 15 and EPIDAT

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

    OpenAIRE

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

    2017-01-01

    Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring...

  7. HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Oscar Peralta-Zaragoza

    2013-01-01

    Full Text Available Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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)....

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

    Science.gov (United States)

    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

  11. A trial of radiofrequency ablation for anal intraepithelial neoplasia.

    Science.gov (United States)

    Goldstone, Robert N; Hasan, Shirin R; Drury, Steven; Darragh, Teresa M; van Zante, Annemieke; Goldstone, Stephen E

    2017-03-01

    Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

  12. The Analysis of Genetic Polymorphism. The Relationship between Interleukin – 4 Polymorphisms and Intraepithelial Cervical Neoplasia

    Directory of Open Access Journals (Sweden)

    Florin STAMATIAN

    2010-09-01

    Full Text Available Objectives: Interleukin 4 plays a critical role in T helper 2 responses to HPV infection and angiogenesis. The present study aim to study the association between the IL4 promoter polymorphism – 590 C>T, respectively VNTR intron 2 polymorphism and cervical intraepithelial neoplasia. Material and method: We have realized a prospective case controls study that included 128 cases of intraepithelial neoplasia positive for HPV HR testing and 111 controls negative for intraepithelial lesion and also negative for HPV HR. Clinical examination was performed on each patient; blood and cervical sample were obtained. Cervical probes were analyzed regarding cytology and HPV HR testing. From peripheral blood DNA sample was obtain followed by genotype analysis for IL4 -590 C>T using PCR RFLP, respectively IL4 70 bp VNTR determined by PCR. Results: The absolute frequency of genotypes for IL4 -590 C>T was T/T-5, C/T-42, C/C-81 in the cases group respectively T/T-2, C/T-32, C/C-77 in the control group. The chi-square test had a value of 0.983 (p=0.321 while considering the presence of a minimum one single variant allele as a risk factor for cervical cancer, respectively 0.926 (p=0.336 for homozygous variant genotype. Odds ratio was 0.761 (95%CI [0.443-1.306] while considering C/T+T/T respectively 2R/3R, 2R/2R as a risk factor, and 0.451 (95%CI 95% [0.086-2.374] - TT respectively 2R/2R as a risk factor. Conclusion: No linear statistical significant association has been found between IL4 polymorphism and cervical neoplasia (p = 0.322.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    2018-01-03

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

  15. Neoplasia intra-epitelial cervical: diagnóstico e tratamento Cervical intraepithelial neoplasia: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Sophie Françoise Mauricette Derchain

    2005-07-01

    Full Text Available O câncer do colo uterino é hoje doença passível de prevenção secundária. Os métodos de detecção das lesões precursoras e da infecção pelo papilomavírus humano, tais como a citologia oncológica e biologia molecular, são de uso mundialmente difundido. Entretanto, ainda há muita controvérsia em relação à aplicação destes métodos na prática ginecológica. Qual o melhor exame ou a melhor associação de exames que podem ser utilizados, com que intervalo e em quais mulheres permanecem questões que com freqüência geram ansiedade nos consultórios ou nas unidades de saúde. Por outro lado, uma vez detectada a infecção viral ou a neoplasia intra-epitelial cervical, o tratamento dessas mulheres ainda não é consensual e muitos fatores interferem na definição da conduta ótima. O tipo de infecção, gravidade da neoplasia intra-epitelial, tipo histológico encontrado, todos estes aspectos tendem a dificultar o planejamento terapêutico. Esta revisão tem como objetivo abordar, dentro do conhecimento atual e baseado nos consensos vigentes no país, vários aspectos relacionados ao rastreamento das lesões cervicais e as possíveis condutas terapêuticas vigentes.Cervical cancer is nowadays a disease amenable to secondary prevention. Methods for the detection of its precursor lesions and human papillomavirus infection, such as cervical cytology and molecular biology, achieved widespread use worldwide. However, there is still too much controversy regarding the use of these methods in gynecological practice. Which is the best examination or the best association of examinations, and the most adequate time intervals to proceed with screening, are still pending questions, generating anxiety in patients and doctors. On the other hand, the management of women who have been diagnosed with viral infection and/or cervical intraepithelial neoplasia is not yet consensual, and several factors may affect the clinical decision on how to

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

    NARCIS (Netherlands)

    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

  17. 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).......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)....

  18. Using gene expression in patients with endometrial intraepithelial neoplasia to assess the risk of cancer

    Directory of Open Access Journals (Sweden)

    Koah Vierkoetter

    2018-05-01

    Full Text Available Patients diagnosed with an endometrial cancer precursor lesion on biopsy may be found to have endometrial cancer at the time of subsequent surgery. The current study seeks to identify patients with endometrial intraepithelial neoplasia (EIN on biopsy that may be harboring an occult carcinoma. Immunohistochemical stains for gene loss of expression (LOE for 6 genes, PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2, were performed on 113 biopsy specimens with EIN. For the 95 patients with follow-up histology, 40 patients had cancer, 41 had EIN, and 14 had normal endometrium. PTEN LOE was found frequently in both EIN and endometrial cancer, and therefore had low positive predictive value. All specimens with ARID1A, MSH6, MSH2, MLH1, or PMS2 LOE on biopsy were subsequently found to have cancer. LOE of any gene was associated with modest sensitivity (0.78 in identifying patients with endometrial cancer who had EIN on biopsy. Further investigation is warranted to determine if gene LOE is a useful clinical tool when evaluating patients with EIN on biopsy. Keywords: Endometrial intraepithelial neoplasia, Endometrial cancer, Gene expression, PTEN, ARID1A, Mismatch repair genes

  19. HPV infection, anal intra-epithelial neoplasia (AIN and anal cancer: current issues

    Directory of Open Access Journals (Sweden)

    Stanley Margaret A

    2012-09-01

    Full Text Available Abstract Background Human papillomavirus (HPV is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM and HIV + groups. HIV + MSM in particular, have anal cancer incidences about three times that of the highest worldwide reported cervical cancer incidences. Discussion There has therefore traditionally been a lack of data from studies focused on heterosexual men and non-HIV + women. There is also less evidence reporting on the putative precursor lesion to anal cancer (AIN – anal intraepithelial neoplasia, when compared to cervical cancer and CIN (cervical intraepithelial neoplasia. This review summarises the available biological and epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and anal cancer amongst traditionally non-high risk groups. Summary There is strong evidence to conclude that high-grade AIN is a precursor to anal cancer, and some data on the progression of AIN to invasive cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

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

    2010-01-01

    The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CI...

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

    NARCIS (Netherlands)

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

    2015-01-01

    BACKGROUND: Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. OBJECTIVES: To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of

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

    NARCIS (Netherlands)

    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

  4. 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

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

    DEFF Research Database (Denmark)

    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...

  6. 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

  7. Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: a prospective study

    NARCIS (Netherlands)

    Wensveen, Celesta; Kagie, Marjolein; Veldhuizen, Roel; de Groot, Christianne; Denny, Lynette; Zwinderman, Koos; Trimbos, Baptist

    2003-01-01

    (1) To assess the prevalence of histologically confirmed cervical intraepithelial neoplasia in patients with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance. (2) To evaluate the role of colposcopy and the presence of human papillomavirus in detecting

  8. Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Munk, Christian; Jensen, Signe Marie

    2016-01-01

    Background: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal...

  9. 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

  10. 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

  11. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    José E. Levi

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  12. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Levi José E.

    2002-01-01

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

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

    Science.gov (United States)

    Barten, G

    1987-01-01

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

  14. Loop electrosurgical excision procedure in Greek patients with vaginal intraepithelial neoplasia and history of cervical cancer.

    Science.gov (United States)

    Terzakis, E; Androutsopoulos, G; Zygouris, D; Grigoriadis, C; Arnogiannaki, N

    2011-01-01

    The aim of our study was to evaluate the therapeutic effectiveness of loop electrosurgical excision procedure (LEEP) in Greek patients with vaginal intraepithelial neoplasia (VAIN) and history of cervical cancer. Between January 2002 and January 2009, eight women with histologically confirmed VAIN and history of cervical cancer were included in our study. For the LEEP procedure we used a high frequency Electrosurgery Unit with at least 80 W output. Complete response rate, at 12 months of follow-up, was 75%. Recurrence rate, at 12 months of follow-up, was 25%. Complete response rate, at 24 months of follow up, was 62.5%. Recurrence rate, at 24 months of follow up, was 37.5%. LEEP may constitute a valuable excisional method for the treatment of VAIN in cases with a history of cervical cancer. It provides an interpretable specimen of the whole lesion within a few minutes. It needs a short period of training and has low cost.

  15. Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah

    2016-01-01

    intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women......Laboratories can nowadays choose from >100 Human Papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART and APTIMA, frequently do not detect...... the same HPV infections. Here, we determined the characteristics of the concordant (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30-65 years (n=2859) and in a concurrent referral population from the same...

  16. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: a cross-sectional study.

    Science.gov (United States)

    Sánchez-Lander, Jorge; Cortiñas, Paula; Loureiro, Carmen Luisa; Pujol, Flor Helene; Medina, Francisco; Capote-Negrín, Luis; Bianchi, Gino; García-Barriola, Victoria; Ruiz-Benni, Angela; Avilán-Rovira, José; Acosta, Humberto

    2012-10-01

    This study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela. Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types. HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P=0.0006). this is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. [Treatment results for different categories of vaginal intraepithelial neoplasia with electrocoagulation, 5-fluorouracil and combined treatment].

    Science.gov (United States)

    Veloz-Martínez, María Guadalupe; Quintana-Romero, Verónica; Contreras-Morales, María del Rosario Sandra; Jiménez-Vieyra, Carlos Ramón

    2015-10-01

    Vaginal intraepithelial neoplasia (VAIN) represents a variety of changes that initiate as an intraepithelial squamous lesion with the possibility of resulting in cancer. To compare the results of the treatment for the different categories of VAIN with electrocoagulation, 5-fluorouracil and combined treatment. Observational an analytical study. We stablished groups according to the category of VAIN evaluating and comparing remission, persistence, recurrence, or progression of the disease ac- cording to the received treatment, with a 1-year follow up. The results were compared by chi2 and Kruskal Wallis. The statistics analysis was done with the SPSS program version 20. One hundred thirty seven patients between 20 and 81 years of age (mean age: 52.49 years) were included. Seventy-four percent of the patients had a history of premalignant or malignant cervical lesions. Seventy-four patients had VAIN I, 34 patients had VAIN II, 22 patients had VAIN III and there were seven cases of vaginal carcinoma in situ. Fifty-eight patients were treated with electrocoagulation, 55 patients were treated with 5-FU, 16 patients had combined treatment, and eight patients received expectant management. Sixty three percent of patients had total remission of the lesion, 34% had persistence and 3% showed progression, and there were no cases of recurrence. Results were better in patients with VAIN I treated with 5-FU (bigger percentage of remission P .026), for the remaining categories of VAIN, no treatment showed superior results. The superior response occurs in patients with VAIN I treated with 5-FU. None of the treatments achieves a 100% remission. The VAIN frequency is high, patients with a history of malignant or premalignant cervical pathology should undergo a closer surveillance through cytocolposcopic control with respect to the remaining population.

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

    Science.gov (United States)

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

    2010-03-01

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

  5. [Shall all lobular intraepithelial neoplasia diagnosed on image-guided biopsy require a surgical management?].

    Science.gov (United States)

    Fischer-Hunsinger, Maeva; Guinebretière, Jean-Marc; Lasry, Serge; Langer, Adriana; Berment, Hélène; Nekka, Ibtissem; Nodiot, Philippe; Cherel, Pascal

    2016-05-01

    Lobular intraepithelial neoplasia (LIN) diagnosed on image-guided biopsy may be associated with an undiagnosed cancer. This is called under-diagnosis. The consequence is that management of these lesions is often surgical. But many surgeries finally are unnecessary. The aim of our study was to define criteria to avoid unnecessary surgery. This is a single-center, retrospective after a database collected prospectively study. Fourteen thousand biopsies were analyzed, including 456 diagnosed NLI. Under-diagnosis rates were analyzed according to many criteria. The average duration of following was 45 months. For atypical lobular hyperplasia (ALH), we obtained 7.6% under-diagnosis and combining several criteria, we got a low risk of cancer (2%). For LCIS, this rate was 23% and any low-risk group could be identified. ALH with calcifications≤20 mm, without any atypical lesion associated, histologically focal and whose removal is representative may be safely observed. For other LIN, surgery remains indicated. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    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.

  7. The use of cold coagulation for the treatment of cervical intraepithelial neoplasia

    LENUS (Irish Health Repository)

    Wyse, A

    2017-05-01

    In 2015, Cold Coagulation was introduced as a treatment for cervical intraepithelial neoplasia (CIN) at our colposcopy clinic. We reviewed the 6-month follow up data of the first 200 women who underwent Cold Coagulation using cytology and HPV status as tests of cure (TOC). A random sample of 200 patients treated by Large Loop Excision of the Transformation Zone (LLETZ) during the same period was used to compare treatment outcome. Six months following treatment,173 (86.5%) of the women treated by CC and 167 (83.5%) treated by LLETZ had negative cytology. (x2= P>0.05). 148 (74%) treated by Cold Coagulation and 166 (83%) treated by LLETZ were HPV negative (x2= P<0.05). One hundred and thirty-nine (70%) women treated by Cold Coagulation and 152 (76%) treated with LLETZ had normal cytology and were HPV negative. This audit of our initial experience supports the observation that Cold Coagulation is as effective as LLETZ in the management of CIN when cervical cytology is used as a test of cure.

  8. Pure Laparoscopic Left Hemihepatectomy for Hepatic Peribiliary Cysts with Biliary Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Akira Umemura

    2016-01-01

    Full Text Available Introduction. Hepatic peribiliary cysts (HPCs usually originate due to the cystic dilatation of the intrahepatic extramural peribiliary glands. We describe our rare experience of pure laparoscopic left hemihepatectomy (PLLH in a patient with HPCs accompanied by a component of biliary intraepithelial neoplasia (BilIN. Case Presentation. A 65-year-old man was referred for further investigation of mild hepatic dysfunction. Contrast-enhanced computed tomography showed dilatation of the left-sided intrahepatic bile duct, and biliary cytology showed class III cells. The patient was highly suspected of having left side-dominated cholangiocarcinoma and underwent PLLH. Microscopic findings revealed multiple cystic dilatations of the extramural peribiliary glands; hence, this lesion was diagnosed as HPCs. The resected intrahepatic bile duct showed that the normal ductal lumen comprised low columnar epithelia; however, front formation on the BilIN was observed in some parts of the intrahepatic bile duct, indicating that the BilIN coexisted with HPCs. Conclusion. We chose surgical therapy for this patient owing to the presence of some features of biliary malignancy. We employed noble PLLH as a minimally invasive procedure for this patient.

  9. Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

    Directory of Open Access Journals (Sweden)

    Nara Chartuni Pereira Teixeira

    Full Text Available OBJECTIVES: To evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN among HIV-infected women. METHODS: Cross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors. RESULTS: CIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1. Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5-10.1, with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2-3.5, and with age < 34 years old (OR 1.5, 95% CI 1.0-2.4. HIV viral load and antiretroviral use were not independent risk factors for CIN. CONCLUSIONS: Severity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.

  10. Plasma Protein Profiles Differ Between Women Diagnosed with Cervical Intraepithelial Neoplasia (CIN 1 and 3

    Directory of Open Access Journals (Sweden)

    Edward E. Partridge

    2006-01-01

    Full Text Available Early detection of precancerous cells in the cervix and their clinical management is the main purpose of cervical cancer prevention and treatment programs. Cytological findings or testing for high risk (HR-human papillomavirus (HPV are inadequately sensitive for use in triage of women at high risk for cervical cancer. The current study is an exploratory study to identify candidate surface-enhanced laser desorption/ionization (SELDI time of flight (TOF mass spectrometry (MS protein profiles in plasma that may distinguish cervical intraepithelial neoplasia (CIN 3 from CIN 1 among women infected with HR-HPV. We evaluated the SELDI-TOF-MS plasma protein profiles of HR-HPV positive 32 women with CIN 3 (cases and 28 women with CIN1 (controls. Case-control status was kept blinded and triplicates of each sample and quality control plasma samples were randomized and after robotic sample preparations were run on WCX2 chips. After alignment of mass/charge (m-z values, an iterative method was used to develop a classifier on a training data set that had 28 cases and 22 controls. The classifier developed was used to classify the subjects in a test data set that has six cases and six controls. The classifier separated the cases from controls in the test set with 100% sensitivity and 100% specificity suggesting the possibility of using plasma SELDI protein profiles to identify women who are likely to have CIN 3 lesions.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

    Science.gov (United States)

    Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2015-06-01

    The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

  14. Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Laura E Pascal

    Full Text Available ELL-associated factor 2 (EAF2 is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/- mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/- mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/- animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors.

  15. 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.

  16. ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

    Science.gov (United States)

    Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

    2009-06-01

    To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

  17. 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.

  18. AKT1 loss correlates with episomal HPV16 in vulval intraepithelial neoplasia.

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    Arucha L Ekeowa-Anderson

    Full Text Available Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV, particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma-HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma- PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN and vulval squamous cell carcinoma (vSCC. We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy.

  19. Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.

    Science.gov (United States)

    Moriya, Toshiyuki; Kimura, Wataru; Semba, Shuho; Sakurai, Fumiaki; Hirai, Ichiro; Ma, Jinfeng; Fuse, Akira; Maeda, Kunihiko; Yamakawa, Mitsunori

    2005-01-01

    Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.

  20. 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

  1. 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.

  2. Association Between Passive Smoking and the Risk of Cervical Intraepithelial Neoplasia 1 in Korean Women

    Directory of Open Access Journals (Sweden)

    Kyung-Jin Min

    2018-01-01

    Full Text Available Background: The role of passive smoking on cervical carcinogenesis remains controversial. We investigated the association of passive smoking with the risk of cervical intraepithelial neoplasia (CIN and cervical cancer. Methods: The study recruited 1,322 women, aged 18–65 with normal cytology (n = 592, CIN1 (n = 420, CIN2/3 (n = 165, and cervical cancer (n = 145 from 2006 to 2009. This study is a cross-sectional analysis using the baseline data from the Korean human papillomavirus (HPV cohort study. Detailed information on smoking behaviors and lifestyles were collected using questionnaires. Multinomial logistic regression analysis was performed to estimate multivariable-adjusted odds ratios (ORs. Results: Passive smoking was not statistically related to the risk of CINs and cervical cancer. However, passive smoking among non-smokers was associated with higher CIN 1 risk (OR 1.53; 95% confidence interval [CI], 1.07–2.18, compared to not passive smoking, after adjusting for demographic factors, lifestyles, and oncogenic-HPV infection status. CIN 1 risk increased with longer time exposed to passive smoking (P for trend <0.0003. Multivariate odds of <2 hours/day of passive smoking and that of ≥2 hours/day of passive smoking were 2.48 (95% CI, 1.49–4.14 and 2.28 (95% CI, 1.21–4.26 for CIN 1, compared to not passive smoking. Conclusions: This study found that passive smoking among non-smoking women is associated with the risk of CIN 1.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  5. 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...

  6. [Effectiveness of human papillomavirus genotyping for detection of high-grade anal intraepithelial neoplasia compared to anal cytology].

    Science.gov (United States)

    Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Fernández-Sánchez, Fernando; Pereda, Teresa; Rivas-Ruiz, Francisco; Fernández-Morano, Teresa; de la Torre-Lima, Javier; Palma, Fermín; Redondo, Maximino; de Troya-Martín, Magdalena

    2016-01-01

    The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

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

    DEFF Research Database (Denmark)

    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...

  8. Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva

    DEFF Research Database (Denmark)

    Faber, Mette T; Sand, Freja Lærke; Albieri, Vanna

    2017-01-01

    In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were...... used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model...... samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions....

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  11. 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

  12. One lesion, one virus: individual components of high-grade anal intraepithelial neoplasia in HIV-positive men contain a single HPV type

    NARCIS (Netherlands)

    Richel, Olivier; Quint, Koen D.; Lindeman, Jan; van Noesel, Carel J. M.; de Koning, Maurits N. C.; van den Munckhof, Henk A. M.; de Vries, Henry J. C.; Prins, Jan M.; Quint, Wim G. V.

    2014-01-01

    High-grade anal intraepithelial neoplasia (AIN) is present in many human immunodeficiency virus (HIV)-positive men who have sex with men. The major etiologic factor is infection with an oncogenic human papillomavirus (HPV) genotype. We investigated whether individual components of high-grade AIN are

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

    DEFF Research Database (Denmark)

    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...

  14. LOCALIZATION OF HUMAN PAPILLOMAVIRUS TYPE-16 DNA USING THE POLYMERASE CHAIN-REACTION IN THE CERVIX UTERI OF WOMEN WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

    NARCIS (Netherlands)

    Cornelissen, M. T.; van den Tweel, J. G.; Struyk, A. P.; Jebbink, M. F.; Briët, M.; van der Noordaa, J.; ter Schegget, J. T.

    1989-01-01

    The localization of human papillomavirus type 16 (HPV-16) DNA throughout the cervix uteri of women with cervical intraepithelial neoplasia (CIN) was studied by utilizing the polymerase chain reaction technique directly on histologically defined sections of paraffin-embedded cervical tissue obtained

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

    DEFF Research Database (Denmark)

    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...

  16. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

    NARCIS (Netherlands)

    van de Nieuwenhof, Hedwig P.; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G.; Massuger, Leon F. A. G.; van der Zee, Ate G. J.; de Hullu, Joanne A.; van Kempen, Leon C. L. T.

    Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a

  17. 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

    Directory of Open Access Journals (Sweden)

    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.

  18. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer.

    Science.gov (United States)

    Bostwick, D G; Alexander, E E; Singh, R; Shan, A; Qian, J; Santella, R M; Oberley, L W; Yan, T; Zhong, W; Jiang, X; Oberley, T D

    2000-07-01

    Oxidative stress results in damage to cellular structures and has been linked to many diseases, including cancer. The authors sought to determine whether the expression of three major antioxidant enzymes, copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and catalase, was altered in human prostate carcinoma and its likely precursor, high grade prostatic intraepithelial neoplasia (PIN). The level of reactive oxygen species damage was evaluated by measuring the expression of the DNA adduct 8-hydroxydeoxyguanosine. The authors evaluated the tissue expression of the antioxidant enzymes in prostate carcinoma by immunohistochemistry, immunogold electron microscopy, and enzymatic assay. The polymerase chain reaction was used to amplify and screen tissue specimens for the genes of SOD1, SOD2, and extracellular SOD (SOD3). Matched paraffin embedded tissue sections were evaluated by RNA in situ hybridization for expression of SOD1 and immunohistochemically for the DNA adduct 8-hydroxydeoxyguanosine. All prostatic tissues, including cancer, displayed immunoreactivity for the three antioxidant enzymes in epithelial cells, with no staining of the stroma, inflammatory cells, or endothelial cells. The number of immunoreactive cells was greater in benign epithelium than in PIN and cancer for each enzyme. The mean percentage and intensity of immunoreactive cells was greatest for SOD2, intermediate for SOD1, and lower for catalase. Staining in cancer was heterogeneous. Immunogold ultrasound studies revealed strong mitochondrial labeling for SOD2, which was greater in benign epithelium than in cancer; SOD1 labeling was invariably weaker, with nuclear labeling in benign epithelium and cytoplasmic labeling in cancer cells. There was no difference in enzyme activity for the three antioxidant enzymes between benign epithelium and cancer. No mutations were found in the 5 exons of SOD1, 5 exons of SOD2, and 3 exons of SOD3, except for 3 of 20 cases with

  19. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    Science.gov (United States)

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

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

    Science.gov (United States)

    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.

  1. Cervical intraepithelial neoplasia; Residual and recurrent disease after laser surgery. Cervikal intraepitelial neoplasi; Persistens og residiv etter laserbehandling

    Energy Technology Data Exchange (ETDEWEB)

    Forsmo, S.; Oeian, P.; Stalsberg, H. (University and Regional Hospital, Tromsoe (Norway))

    1992-03-01

    Between 1983 and 1988, 402 women with ages ranging from 18 to 73 years were treated for cervical intraepithelial neoplasia using the CO{sub 2}-laser. 89 patients underwent vaporization and 313 conization. Preoperative biopsy examination showed CIN III in 214 patients. Five cases of invasive cancer were diagnosed, either preoperatively after conization or on both occasions. At the first postoperative examination residual disease was found in 21 patients of the vaporization group and in 13 patients of the conization group. Later examinations revealed recurrence in 10 patients in the vaporization group and in 13 patients in the conization group. Median time for recurrence was 11 months. 30 patients were treated twice or more. No case of invasive cancer was diagnosed after treatment. 18 refs., 6 tabs.

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

    DEFF Research Database (Denmark)

    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....

  3. 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...

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

    DEFF Research Database (Denmark)

    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...

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Freqüência de Neoplasia Intra-epitelial Cervical em Portadoras do Vírus da Imunodeficiência Humana Frequency of Cervical Intraepithelial Neoplasia in Human Immunodeficiency Virus-infected Women

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    Antonio Pedro Flores Auge

    2000-10-01

    Full Text Available Objetivo: verificar a freqüência de neoplasia intra-epitelial cervical (NIC em mulheres infectadas pelo vírus da imunodeficiência humana (HIV. Métodos: foram estudadas 99 mulheres HIV-soropositivas; o diagnóstico da infeccão pelo HIV foi realizado por meio de dois testes ELISA, complementados por teste Western blot ou de imunofluorescência indireta. Como grupo controle foram analisadas 104 mulheres que não apresentavam positividade no teste ELISA. Em ambos os grupos o rastreamento de NIC foi realizado por meio da associação de colpocitologia oncológica e colposcopia. Nos casos em que a colposcopia revelou existência de zonas de transformação anormal, o diagnóstico de NIC foi realizado mediante biopsia dirigida, complementada ou não por conização. Resultados: em 15 das 99 pacientes do grupo de estudo (15,2% foi encontrada neoplasia intra-epitelial cervical, sendo dez casos de NIC I, um de NIC II e quatro de NIC III. Entre as 104 mulheres do grupo controle, quatro (3,8% eram portadoras de neoplasia intra-epitelial cervical, encontrando-se um caso de NIC I e três de NIC III. Conclusão: a análise comparativa dos resultados evidenciou que a freqüência de neoplasia intra-epitelial cervical foi significantemente mais elevada entre as pacientes infectadas pelo HIV.Purpose: to verify the frequency of cervical intraepithelial neoplasia in human immunodeficiency virus (HIV ¾ infected women. Methods: ninety-nine HIV-seropositive women were studied. The diagnosis of the HIV infection was established through two ELISA tests complemented by Western blot test or indirect immunofluorescence test. As control group, 104 women whose ELISA test was not positive were analyzed. The investigation of cervical intraepithelial neoplasia was achieved by association of Pap smear and colposcopy in both groups. In the cases where colposcopy revealed existence of abnormal transformation zones, NIC diagnosis was obtained through colposcopy-guided biopsy

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

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    Jastreboff, A; Cymet, T

    2002-01-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially d...

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

    Science.gov (United States)

    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.

  13. 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

  14. 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.

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

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

    2012-07-01

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

  16. Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

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    Gajjar, Ketan; Martin-Hirsch, Pierre P L; Bryant, Andrew; Owens, Gemma L

    2016-07-18

    Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral

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

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    Jastreboff, A M; Cymet, T

    2002-04-01

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

  18. Características de um grupo de adolescentes com suspeita de neoplasia intra-epitelial cervical Characteristics of a group of adolescents with suspected cervical intraepithelial neoplasia

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    Maria Isabel do Nascimento

    2005-10-01

    suspected cervical neoplasia and to compare it with young adult women. METHODS: a cross-sectional, retrospective study that analyzed 366 medical records of females referred to clarify diagnosis of the suspected cervical neoplasia. The patients had been classified into two groups defined by age. The Adolescent group was composed of 129 females between 13 and 19 years and the Adult group was composed of 237 females between 20 and 24 years. Data were analyzed statistically by the prevalence ratio (PR, respective confidence intervals (CI at 95% for each variable, chi2 test, or Fisher exact test used to compare proportion. RESULTS: the first sexual intercourse coitarche occurred on average at 15.0 years in the Adolescent group and 16.6 years in the Adult group. The possibility of diagnosis of cytological alterations in the first Papanicolaou smears (PR=2.61; CI 95%: 2.0-3,4, the condition of non-clarified cervical intraepithelial neoplasia (CIN (PR=1.78; CI 95%: 1.26-2,52, and the colposcopic impressions of low grade (PR=1.42; CI 95%: 1.08-1.86 were statistically significant in the Adolescent group. The histopathologic analysis did not show differences at any grade of CIN. However, two cases of microinvasive carcinoma, one in each group, and three cases of clinical invasive carcinoma in the Adult group were identified. CONCLUSION: our study suggests that cervical cancer is rare among adolescents, but we verified that alterations associated with it occurred even in younger women. The evaluation of cervical intraepithelial neoplasia with the careful application of the same tools used for adult women was appropriate also in adolescence.

  19. 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.

  20. 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.

  1. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2010-01-01

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

  4. Aberrant Methylation of Preproenkephalin and p16 Genes in Pancreatic Intraepithelial Neoplasia and Pancreatic Ductal Adenocarcinoma

    OpenAIRE

    Fukushima, Noriyoshi; Sato, Norihiro; Ueki, Takashi; Rosty, Christophe; Walter, Kimberly M.; Wilentz, Robb E.; Yeo, Charles J.; Hruban, Ralph H.; Goggins, Michael

    2002-01-01

    Pancreatic intraductal neoplasia (PanIN) is thought to be the precursor to infiltrating pancreatic ductal adenocarcinoma. We have previously shown that the preproenkephalin (ppENK) and p16 genes are aberrantly methylated in pancreatic adenocarcinoma. In this study we define the methylation status of the ppENK and p16 genes in various grades of PanINs. One hundred seventy-four samples (28 nonneoplastic pancreatic epithelia, 7 reactive epithelia, 29 PanIN-1A, 48 PanIN-1B, 27 PanIN-2, 14 PanIN-3...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  7. [High-risk human papilloma virus and cervical intraepithelial neoplasia in women at 2 hospitals in Mexico City].

    Science.gov (United States)

    Hernández-Hernández, Dulce Ma; García-Carrancá, Alejandro; Guido-Jiménez, Miriam C; González-Sánchez, José Luis; Cruz-Talonia, Fernando; Apresa-García, Teresa; Martínez-Elizondo, Olga A; Ornelas-Bernal, Laura; Alvarado-Cabrera, Isabel; Muñoz, Sergio

    2002-01-01

    To determine the high risk HPV (HR-HPV) association with Cervical Intraepithelial Neoplasia (CIN) in women of two Dysplasia Clinics in Mexico City. Prolective case-control study was done. Women with and without security affiliation attended in Instituto Mexicano del Seguro Social (Hospital 1) and Hospital General de México (Hospital 2) were included in the study. Cases were women with histopathologic diagnosis of CIN and controls were women with negative dysplasia in cytologic study (Pap). Information was obtained by direct interview. HR-HPV was determined by Hybrid Capture II assay, in cervical samples. Bivariate and logistic regression analysis was done. One hundred and two cases and 192 controls from Hospital 1 and 89 cases and 66 controls from Hospital 2 were included. 83.3% and 77.3% of women from Hospital 1 and 2 respectively were positive to HR-HPV. The association HR-HPV and CIN in Hospital 1 was ORa = 40.6, C.I. 95% = 17-96.8; while in Hospital 2 there was not association. Age was an effect modifier in the HR-HVP and CIN association, in Hospital 1. It was observed a correlation between viral load and CIN degree. The HR-HPV infection frequency in controls and CIN I was higher than the reported in other studies. Age was a modifier in the HR-HPV association and CIN. In dysplasia clinics without medical referral system of patients is possible to observe similar risk factors to cervical cancer.

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?

    Science.gov (United States)

    Mitra, Anita; MacIntyre, David A; Marchesi, Julian R; Lee, Yun S; Bennett, Phillip R; Kyrgiou, Maria

    2016-11-01

    The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.

  12. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008

    DEFF Research Database (Denmark)

    Nielsen, Ann; Plum, Christian Edinger Munk; Kjaer, Susanne K

    2012-01-01

    The aim of the study was to determine the incidences of anal cancer and high-grade anal intraepithelial neoplasia (AIN2/3) over time in Danish women and men. Describing the burden of anal cancer and AIN may be valuable in future evaluations of the human papillomavirus (HPV) vaccine. We included all...... anal cancers in the Danish Cancer Register in the period 1978-2008 and all cases of AIN2/3 in the Danish Registry of Pathology. Overall and age-, period- and histology-specific incidence rates were estimated. During the 30-year period, 2187 anal cancers were identified, two thirds of which were...... in women. Between 1978-1982 and 2003-2008, the age-standardized incidence rate of anal cancer increased from 0.68 to 1.48 per 100 000 person-years in women and from 0.45 to 0.80 per 100 000 person-years in men. Although there is no systematic screening for AIN in Denmark, we nevertheless identified 608...

  13. An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

    Science.gov (United States)

    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.

  14. Factors associated with colposcopy-histopathology confirmed cervical intraepithelial neoplasia among HIV-infected women from Rio De Janeiro, Brazil.

    Directory of Open Access Journals (Sweden)

    Angela Cristina Vasconcelos de Andrade

    Full Text Available INTRODUCTION: Despite the availability of preventive strategies (screening tests and vaccines, cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV and thus development of cervical squamous intraepithelial neoplasia (CIN. METHODS: Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ. At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. RESULTS: The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28-41 years. The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥ 35 years (aPR  =  3.22 95%CI 1.23-8.39, current tobacco use (aPR  =  3.69 95%CI 1.54-8.78, nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR  =  6.03 95%CI 1.50-24.3 and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR  =  2.68 95%CI 0.99-7.24. DISCUSSION: Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical

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

    Directory of Open Access Journals (Sweden)

    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

  16. Outcomes after management of young women with cervical intraepithelial neoplasia 2 with a 6-month observation protocol.

    Science.gov (United States)

    Bleecker, Elizabeth; Koehler, Elizabeth; Smith, Jennifer; Budwit, Debra; Rahangdale, Lisa

    2014-01-01

    Recommendations regarding treatment of cervical intraepithelial neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2 may be offered observation with Pap smears and colposcopy every 6 months instead of immediate excision or ablation of disease. The purpose of this study was to observe patient follow-up during the initiation of this management protocol for young women with CIN 2. This was a retrospective review of clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and planned follow-up at UNC between July 2009 and August 2010. A chart review for clinical variables, follow-up visits, and progression of disease was conducted. Primary analysis determined the rate of follow-up and pathology at 6 months. Secondary analysis investigated risk factors for incomplete follow-up. Seventy women met inclusion criteria; 46 were managed with observation. Twenty-eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical variables did not reach statistical significance in predicting the likelihood of completion of a follow-up visit, although there was a trend toward greater follow-up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84-34.78). Approximately half (52.4%; 11/21) of women with a completed cervical biopsy demonstrated regression of disease during the study period. On the basis of these data, follow-up in this population was unpredictable based on basic demographic or clinical factors that we often use to judge likelihood of compliance with medical recommendations. The percentage of patients with regression at follow-up was as expected from the natural history of CIN 2.

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

    Science.gov (United States)

    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.

  18. Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck, E-mail: khbaek@skku.edu

    2013-10-11

    Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

  19. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    International Nuclear Information System (INIS)

    García-Espinosa, Benjamín; Moro-Rodríguez, Ernesto; Álvarez-Fernández, Emilio

    2012-01-01

    Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited

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

    Science.gov (United States)

    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.

  1. Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence.

    Science.gov (United States)

    Biankin, Andrew V; Kench, James G; Biankin, Sandra A; Lee, C-Soon; Morey, Adrienne L; Dijkman, Floriaan P; Coleman, Maxwell J; Sutherland, Robert L; Henshall, Susan M

    2004-09-01

    The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.

  2. Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

    International Nuclear Information System (INIS)

    Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck

    2013-01-01

    Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15 INK4b in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras G12D . In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15 Ink4b tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals

  3. Young women, cervical intraepithelial neoplasia and human papillomavirus: risk factors for persistence and recurrence.

    Science.gov (United States)

    Frega, Antonio; Stentella, Patrizia; De Ioris, Andrea; Piazze, Juan Josè; Fambrini, Massimiliano; Marchionni, Mauro; Cosmi, Ermelando Vinicio

    2003-07-10

    Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections (STIs) in young women. They can occur in one or multiple areas of the female genitalia. Usually, the vulva is the initial site of implantation for HPV. The purpose of our study is to evaluate the epidemiological aspects, incidence of single or multiple lesions in the lower genital tract, correlation between sexual behaviour and their localization and behaviour risk factors for persistence and recurrence of HPV lesions and cervical intraepithelial lesion (CIN) in a long-term follow-up among young women. We recruited 268 patients aged 11-21 years who previously had cytology and/or physical examination suspicious for HPV infection. The women were interviewed and asked information about lifestyle, sexual behaviour, work, personal or family history of genital warts and school attendance. We considered individuals to be 'smokers' if they smoked more than five cigarettes/day. No specific data were recorded about oral contraception, nevertheless, no woman had used oral contraceptives (OCs) for more than 2 years. Young women included in the study were between the age of 12 and 21 years who had HVP lesions after entry examinations and had undergone no treatment for HPV lesions prior to entry. Other exclusion criteria relevant to this study included cervical excisional treatment prior to entry or later. Two hundred and thirty-four young women were included in our study group. Our diagnostic schedule for a complete evaluation included exo- and endocervical cytology, colposcopy, directed biopsy and microcolpohysteroscopy. The treatment was performed with a LASER CO2 Coherent 400, model 451, with Zeiss photocolposcopy attachment. The finding that, among 126/234 (53.8%) adolescents using contraceptives, only 85 (36.3%) have used condom, the only barrier form of contraceptive effectively protecting against virus, shows a low awareness of the high risk for contracting HPV infection among

  4. 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

    DEFF Research Database (Denmark)

    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...

  5. Association of TAP Gene Polymorphisms and Risk of Cervical Intraepithelial Neoplasia

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    Camilla Natter

    2013-01-01

    Full Text Available Background. Transporter associated with antigen processing (TAP is responsible for peptide loading onto class I major histocompatibility complex (MHC-I molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and contributes to successful eradication of HPV. TAP polymorphisms could have an important impact on the course of HPV infection. Objective. The aim of this study is to evaluate the association between five TAP gene polymorphisms and the risk of CIN. Methods. This case-control study investigated five common TAP polymorphisms in TAP1 (1341 and 2254 and TAP2 (1135, 1693, and 1993 in 616 women with CIN and 206 controls. Associations between gene polymorphisms and risk of CIN were analysed by univariate and multivariable models. The combined effect of the five TAP gene polymorphisms on the risk for CIN was investigated by haplotype analysis. Results. No significant difference in genotype distribution of the five TAP polymorphisms was observed in women with CIN and controls. Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP polymorphisms t1135-t1341-t1693-t1993-t2254 had a significantly lower risk for CIN, compared to women with the haplotype wt-wt-wt-wt-wt (; OR 0.5 []. Conclusion. Identification of this haplotype combination could be used to identify women, less susceptible for development of CIN following HPV infection.

  6. 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.

  7. Associations between methylation of paternally expressed gene 3 (PEG3, cervical intraepithelial neoplasia and invasive cervical cancer.

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    Monica D Nye

    Full Text Available Cytology-based screening for invasive cervical cancer (ICC lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR and confidence intervals (CI 95% for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1. HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6 and ICC (OR = 29.5, 95% CI 6.3-38.4. Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs methylation (r = 0.34 p<0.0001, while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047. Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC, especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with

  8. 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

  9. 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

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

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    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

  11. 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

  12. Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings.

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    Yamal, Jose-Miguel; Zewdie, Getie A; Cox, Dennis D; Atkinson, E Neely; Cantor, Scott B; MacAulay, Calum; Davies, Kalatu; Adewole, Isaac; Buys, Timon P H; Follen, Michele

    2012-04-01

    Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training.

  13. 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.

    2013-01-01

    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

  14. 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.

  15. Duração da Neoplasia Intra-Epitelial e do Carcinoma Invasor do Colo Uterino: Estudo Epidemiológico Duration of Intraepithelial Neoplasia and Invasive Carcinoma of the Cervix in Relation to Age at Diagnosis

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    Luiz Carlos Zeferino

    1998-12-01

    Full Text Available Objetivo: estimar a duração e o tempo de evolução da neoplasia do colo uterino, a partir da infecção por papilomavírus humano (HPV até as formas invasoras avançadas, tomando como parâmetro a idade média ao diagnóstico. Método: estudo observacional-transversal que incluiu 1.177 mulheres com infecção por HPV, 1.561 com neoplasia intra-epitelial cervical (NIV e 773 com carcinoma invasor. Resultados: não houve diferença estatisticamente significante entre as médias de idade ao diagnóstico da NIC 1 e NIC 2. A duração da NIC 2 foi 2,2 anos e da NIC 3 foi 10,3 anos, sendo 4,1 anos como displasia grave e 6,2 anos como carcinoma in situ (CIS. A duração da lesão intra-epitelial escamosa de alto grau foi 12,5 anos e do carcinoma invasor estádio Ia, Ib e II foram, respectivamente, 3,0, 2,7 e 3,7 anos. Conclusões: de acordo com os resultados deste estudo, as NIC 1 e NIC 2 originam-se diretamente da infecção por HPV e a maioria das NIC 2 seria uma lesão transiente. A lesão de maior duração é o CIS e o tempo médio do período subclínico da neoplasia do colo uterino é de 18,2 anos. Estes resultados são discutidos em função do conhecimento mais atual da história natural do carcinoma do colo uterino e de outros estudos que estimaram a duração desta neoplasia.Purpose: to estimate the duration of cervical neoplasia from human pappilomavirus (HPV infection to advanced invasive carcinoma, using as paremeter the mean age of the women at diagnosis. Methods: this cross-sectional study included 1,177 women with HPV infection, 1,561 with cervical intraepithelial neoplasia (CIN and 773 with invasive carcinoma. Results: the mean ages of CIN 1 and CIN 2 on diagnosis were not statistically different. The mean duration of CIN 2 was 2.2 years. The mean duration of CIN 3 was 10.3 years, with 4.1 years as severe dysplasia and 6.2 years as carcinoma in situ (CIS. The mean duration of high grade squamous intraepithelial lesions was 12

  16. 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.

  17. 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.

  18. Recurrence/persistence of cervical intraepithelial neoplasia after undergoing a LEEP conization at Instituto Nacional de Enfermedades Neoplásicas

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    Gino Venegas-Rodríguez

    2017-01-01

    Full Text Available Objective: To determine the incidence of recurrence/persistence of cervical intraepithelial neoplasia (CIN in patients who underwent a loop electrosurgical excision procedure (LEEP at the Department of Gynecologic Oncology of Instituto Nacional de Enfermedades Neoplásicas (INEN. Materials and methods: A retrospective cohort study in which medical records of patients who underwent a LEEP conization from January 2002 to December 2003 were examined. After the LEEP conization, patients were divided into two groups: one with positive margin and another one with negative margin. Follow-up was performed every 3 months and consisted of a physical examination, Pap test and colposcopy. The outcome was recurrence of CIN. To assess the risk of CIN recurrence among the study groups, relative risk (RR and its respective 95% confidence interval (CI were calculated. Results: A total of 451 patients underwent a LEEP conization during the study period. The mean age was 35.32 years old, the mean number of sexual partners was 2.1 and the mean number of children was 2.7. One hundred and nine (109 patients (25% showed a positive margin and 342 (75% showed a negative one. Out of these subjects, only 94 and 102, respectively, met the eligibility criteria and were followed. The mean follow-up period was 21.74 months. The incidence of recurrence/persistence in patients with positive margin was 5.5%, while the incidence of recurrence/persistence in the group of patients with negative margin was 1.96%. We found no significant differences in the risk of CIN recurrence in the group of patients with positive margin versus patients with negative margin. RR = 2.7, 95% CI (0.41 to 33.8. Conclusion: There was no significant difference in the incidence of cervical intraepithelial neoplasia between patients with positive margin and patients with negative margin.

  19. 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.

  20. 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.

    Science.gov (United States)

    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.

  1. 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.

  2. Quality of life and female sexual function after skinning vulvectomy with split-thickness skin graft in women with vulvar intraepithelial neoplasia or vulvar Paget disease.

    Science.gov (United States)

    Lavoué, V; Lemarrec, A; Bertheuil, N; Henno, S; Mesbah, H; Watier, E; Levêque, J; Morcel, K

    2013-12-01

    Vulvar intraepithelial neoplasia (VIN) and vulvar Paget disease are managed with either vulvectomy, destructive treatments (laser, antimitotic drugs) or immunostimulants. All these options are associated with functional complications. The purpose of this study was to evaluate the surgical technique consisting of skinning vulvectomy with split-thickness skin graft, and its effect on overall quality of life and sexual function. A retrospective study was conducted on thirteen patients who underwent skinning vulvectomy with split-thickness skin graft between 1999 and 2009. Overall quality of life and sexual function were assessed with the Medical Outcome Study Short Form 36 (MOS SF-36) and Female Sexual Function Index (FSFI), respectively. The median age of patients was 54 (range: 33-77) years. Three patients had Paget disease and 10 patients had VIN lesions. The excision margins were clear in 46% of cases. The incidence of occult cancer was 31%. The mean follow-up period was 77 (±35) months. Four patients experienced a relapse of their intraepithelial disease. The mean disease-free survival was 58 (±44) months. There was no significant difference in MOS SF-36 scores between the study population and the general population. The patients assessed with the FSFI regained normal sexual function after the surgical procedure. Skinning vulvectomy with split-thickness skin graft is a feasible technique yielding good results in terms of quality of life and sexual function. It enables occult cancer to be diagnosed in patients with VIN or Paget disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. 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

    Science.gov (United States)

    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

  4. The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

    Science.gov (United States)

    Burgos, J; Curran, A; Landolfi, S; Navarro, J; Tallada, N; Guelar, A; Crespo, M; Ocaña, I; Ribera, E; Falcó, V

    2016-08-01

    Electrocautery is one of the main treatment options for high-grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN. An observational study of HIV-infected men who have sex with men (MSM) who underwent screening for anal dysplasia was carried out. The on-treatment effectiveness of electrocautery was evaluated (according to biopsy findings measured 6-8 weeks after treatment) in patients with HGAIN. A complete response was defined as resolution of anal intraepithelial neoplasia (AIN), a partial response as regression to low-grade AIN and recurrence as biopsy-proven HGAIN during follow-up. From May 2009 to November 2014, 21.9% (126 of 576) of patients screened were found to have HGAIN. Electrocautery effectiveness was evaluated in 83 patients. A complete response was observed in 27 patients [32.5%; 95% confidence interval (CI) 23.4-53.2%], a partial response in 28 patients (33.7%; 95% CI 24.5-44.4%) and persistence in 28 patients (33.7%; 95% CI 24.5-44.4%). The patients with the most successful results (81.8%) required two to four sessions of electrocautery. After a mean follow-up of 12.1 months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9 months (95% CI 22-37.7 months). No patient progressed to invasive cancer during the study or developed serious adverse events after treatment. No factors associated with poor response or recurrences were observed. Although electrocautery is the standard treatment for anal dysplasia, almost 50% of patients with HGAIN in our study did not respond or relapsed. New treatment strategies are necessary to optimize the management of anal dysplasia. © 2015 British HIV Association.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  7. 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

  8. Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Horn, L.C.; Reichert, A.; Oster, A.

    2008-01-01

    The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is...... immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology Udgivelsesdato: 2008/4......The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides......) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch...

  9. Efficacy of human papillomavirus l1 protein vaccines (cervarix and gardasil in reducing the risk of cervical intraepithelial neoplasia: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haghshenas

    2017-01-01

    Full Text Available Human papillomavirus (HPV can induce cervical intraepithelial neoplasia (CIN. Vaccination against HPV can play an important role in CIN prevention. This study aims to estimate the efficacy of L1 protein vaccines (Cervarix and Gardasil in CIN 1, 2, 3 risk reduction using meta-analysis. Relevant articles were identified by two independent researchers searching international databanks. After application of inclusion/exclusion criteria and quality assessment, eligible articles were entered into the final meta-analysis. Inverse variance method and fixed effect model were used to combine the results of the primary studies. The heterogeneity between the results was assessed using Cochrane and I2 indices. Of 11,530 evidence identified during the primary search, three papers were found eligible for meta-analysis, including 7213 participants in the intervention groups and 7170 healthy controls. The efficacy (95% confidence interval of HPV 6, 11, 16, 18 monovalent and quadrivalent vaccines against CIN 1, CIN 2, and CIN 3 were estimated as of 95% (88–98, 97% (85–99, and 95% (78–99, respectively. This study showed that L1 protein vaccines Cervarix and Gardasil are highly protective vaccines playing an effective role in the prevention of HPV 6, 11, 16, 18 which are responsible for CIN 1, CIN 2, and CIN 3.

  10. Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.

    Science.gov (United States)

    Santesso, Nancy; Mustafa, Reem A; Wiercioch, Wojtek; Kehar, Rohan; Gandhi, Shreyas; Chen, Yaolong; Cheung, Adrienne; Hopkins, Jessica; Khatib, Rasha; Ma, Bin; Mustafa, Ahmad A; Lloyd, Nancy; Wu, Darong; Broutet, Nathalie; Schünemann, Holger J

    2016-03-01

    Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated. To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3. Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used. Studies of nonpregnant women 18 years or older not previously treated for CIN were included. Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy. Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

    Directory of Open Access Journals (Sweden)

    Márcia Antoniazi Michelin

    2015-03-01

    Full Text Available Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+ lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN. We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  14. Histomorfometria, apoptose e proliferação celular em neoplasias intraepiteliais do colo uterino Histomorphometry, apoptosis and cell proliferation in cervical intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Rodrigo Tadeu de Puy e Souza

    2011-12-01

    alterations. Accumulation of such mutations and unbalance of genomic homeostasis induce changes in certain genes as well as affect cell proliferation and apoptosis. Immunohistochemical markers of cellular proliferation, apoptosis and cell survival in cervical intraepithelial lesions still require morphometric studies in order to define their role in the development of dysplasias caused by invasive carcinoma. OBJECTIVES: In order to better understand the processes of cellular proliferation, apoptosis and epithelial turn over in such precursory lesions, histomorphometric evaluation for mitosis and apoptosis as well as immunohistochemical reactions for Bax, Bcl-2 and Ki-67 proteins (reactivity, localization and intensity were carried out in cervical biopsies. METHODS: Samples were split into four groups: 1. cervicitis (n = 20; 2. light dysplasia (n = 20; 3. moderate dysplasia (n = 20; 4. severe dysplasia (n = 20. RESULTS: Intense proliferation and apoptosis were observed in lesions with high, extensive, intense, and diffuse Ki-67 and Bax immunolabeling. Proliferation and apoptosis were mild or null in groups 1 and 2. Bcl-2 immunolabeling was more intense in high degree lesions and mild in the other groups. Extensive Ki-67 and Bax immunolabeling suggests an increased cellular turn over, which was also corroborated by histomorphometry. The more severe the dysplasia is the higher Bcl-2 expression. CONCLUSION: These data indicate that the pre-neoplastic process is dynamic and is concomitant with apoptosis and mitosis.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  17. Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Fiji.

    Science.gov (United States)

    Tabrizi, Sepehr N; Law, Irwin; Buadromo, Eka; Stevens, Matthew P; Fong, James; Samuela, Josaia; Patel, Mahomed; Mulholland, E Kim; Russell, Fiona M; Garland, Suzanne M

    2011-09-01

    There is currently limited information about human papillomavirus (HPV) genotype distribution in women in the South Pacific region. This study's objective was to determine HPV genotypes present in cervical cancer (CC) and precancers (cervical intraepithelial lesion (CIN) 3) in Fiji. Cross-sectional analysis evaluated archival CC and CIN3 biopsy samples from 296 women of Melanesian Fijian ethnicity (n=182, 61.5%) and Indo-Fijian ethnicity (n=114, 38.5%). HPV genotypes were evaluated using the INNO-LiPA assay in archival samples from CC (n=174) and CIN3 (n=122) among women in Fiji over a 5-year period from 2003 to 2007. Overall, 99% of the specimens tested were HPV DNA-positive for high-risk genotypes, with detection rates of 100%, 97.4% and 100% in CIN3, squamous cell carcinoma (SCC) and adenosquamous carcinoma biopsies, respectively. Genotypes 16 and 18 were the most common (77%), followed by HPV 31 (4.3%). Genotype HPV 16 was the most common identified (59%) in CIN3 specimens, followed by HPV 31 (9%) and HPV 52 (6.6%). Multiple genotypes were detected in 12.5-33.3% of specimens, depending on the pathology. These results indicated that the two most prevalent CC-associated HPV genotypes in Fiji parallel those described in other regions worldwide, with genotype variations thereafter. These data suggest that the currently available bivalent and quadrivalent HPV vaccines could potentially reduce cervical cancers in Fiji by over 80% and reduce precancers by at least 60%.

  18. Quantitative attenuation analysis for identification of early Barrett's neoplasia in volumetric laser endomicroscopy

    Science.gov (United States)

    Swager, Anne-Fre; Faber, Dirk J.; de Bruin, Daniel M.; Weusten, Bas L.; Meijer, Sybren L.; Bergman, Jacques J.; Curvers, Wouter L.; van Leeuwen, Ton G.

    2017-08-01

    Early neoplasia in Barrett's esophagus (BE) is difficult to detect. Volumetric laser endomicroscopy (VLE) incorporates optical coherence tomography, providing a circumferential scan of the esophageal wall layers. The attenuation coefficient (μVLE) quantifies decay of detected backscattered light versus depth, and could potentially improve BE neoplasia detection. The aim is to investigate feasibility of μVLE for identification of early BE neoplasia. In vivo and ex vivo VLE scans with histological correlation from BE patients ± neoplasia were used. Quantification by μVLE was performed manually on areas of interest (AoIs) to differentiate neoplasia from nondysplastic (ND)BE. From ex vivo VLE scans from 16 patients (13 with neoplasia), 68 AoIs were analyzed. Median μVLE values (mm-1) were 3.7 [2.1 to 4.4 interquartile range (IQR)] for NDBE and 4.0 (2.5 to 4.9 IQR) for neoplasia, not statistically different (p=0.82). Fourteen in vivo scans were used: nine from neoplastic and five from NDBE patients. Median μVLE values were 1.8 (1.5 to 2.6 IQR) for NDBE and 2.1 (1.9 to 2.6 IQR) for neoplasia, with no statistically significant difference (p=0.37). In conclusion, there was no significant difference in μVLE values in VLE scans from early neoplasia versus NDBE. Future studies with a larger sample size should explore other quantitative methods for detection of neoplasia during BE surveillance.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

    Science.gov (United States)

    Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

    2018-01-01

    The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

  1. 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)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  4. Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia: a nationwide population-based cohort study in Denmark.

    Science.gov (United States)

    Svahn, M F; Munk, C; Jensen, S M; von Buchwald, C; Frederiksen, K; Kjaer, S K

    2016-07-01

    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. We established a nationwide cohort of approximately 2,500,000 Danish women born in 1918-1990. By linking the cohort to population-based health registries, we obtained information on CIN3/AIS, cancer, migration, death, education, and smoking. Cox proportional hazards models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the association between CIN3/AIS and risk of head-and-neck squamous cell carcinoma (HNSCC). HRs were presented for any HNSCC and for four subgroups categorized by their anticipated degree of association with human papillomavirus (HPV). A history of CIN3/AIS was significantly associated with an increased overall relative risk of HNSCC after adjustment for year of birth, attained age, and length of education. The risk was especially high for sites anticipated to be strongly associated with HPV (e.g. base of tongue, tonsils) (HR, 2.49; 95% CI, 1.84-3.36). Lower risks were found for sites anticipated to be not or weakly associated with HPV (e.g. nasal cavity, middle ear, sinuses) (HR, 1.29; 95% CI, 0.61-2.76). Women with a history of CIN3/AIS have a significantly higher risk of HNSCC than women without such a history. The increased relative risk persisted for at least 20years after the CIN3/AIS diagnosis. Women with CIN3/AIS may be more susceptible to the consequences of HPV and/or may have higher risk behavior, such as smoking. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Cervical cancer screening and treatment of cervical intraepithelial neoplasia in female sex workers using “screen and treat” approach

    Directory of Open Access Journals (Sweden)

    Joshi S

    2015-05-01

    Full Text Available Smita Joshi,1 Vinay Kulkarni,2 Trupti Darak,2 Uma Mahajan,1 Yogesh Srivastava,3 Sanjay Gupta,3 Sumitra Krishnan,1 Mahesh Mandolkar,2 Alok Chandra Bharti31Hirabai Cowasji Jehangir Medical Research Institute (HCJMRI, Jehangir Hospital Premises, Pune, Maharashtra, India; 2Prayas Health Group, Amrita Clinic, Pune, India; 3Institute for Cytology and Preventive Oncology, Indian Council of Medical Research, New Delhi, IndiaObjective: Female sex workers (FSWs are at an increased risk of human immunodeficiency virus (HIV as well as human papillomavirus (HPV infections and thus have an increased risk of cervical intraepithelial neoplasia (CIN and cervical cancer. We evaluated the feasibility of “screen and treat approach” for cervical cancer prevention and the performance of different screening tests among FSWs.Methods: Women were screened using cytology, VIA (visual inspection with acetic acid, and VILI (visual inspection with Lugol’s iodine and underwent colposcopy, biopsy, and immediate treatment using cold coagulation, if indicated, at the same visit.Results: We screened 300 FSWs of whom 200 (66.67% were HIV uninfected and 100 (33.34% were HIV infected. The overall prevalence of CIN 2–3 lesions was 4.7%. But all women with CIN 2–3 lesions were HIV infected, and thus the prevalence of CIN 2–3 lesions in HIV-infected FSWs was 14/100 (14%, 95% confidence interval: 7.2–20.8. All of them screened positive by all three screening tests. Cold coagulation was well tolerated, with no appreciable side effects.Conclusion: Cervical cancer prevention by “screen and treat” approach using VIA, followed by ablative treatment, in this high-risk group of women is feasible and can be implemented through various targeted intervention programs. Keywords: cytology, VIA, VILI, CIN, cold coagulation, cervical cancer, HPV, FSWs

  6. EVALUATION OF P16INK4A PROTEIN AS A BIOMARKER FOR CERVICAL INTRAEPITHELIAL NEOPLASIA AND SQUAMOUS CELL CARCINOMA OF THE UTERINE CERVIX

    Directory of Open Access Journals (Sweden)

    Biljana Đorđević

    2011-06-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well known. Interaction of HPV proteins with cellular regulatory proteins leads to up regulation of p16INK4A. The aim of this study was to evaluate p16INK4A protein as a biomarker for CIN lesions and squamous cell carcinoma on biopsy specimens of patients who underwent biopsy of the uterine cervix due to abnormal cytological finding.The authors analyzed biopsies from 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix. Expression of p16INK4A in CIN and invasive squamous cell carcinoma was immunohistochemically analyzed by using monoclonal anti-p16INK4A antibody.A total of 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix (mean age 40.2±11.5 years, range 20-74 years were analyzed. CIN I lesions were found in 27 (54%, CIN II/CIN III lesions in 9 (18%, and invasive squamous cell carcinoma in 14 (28% patients. Differences in the expression of p16INK4A between CIN I, CIN II/CIN III and squamous cell carcinoma were statistically significant (p<0.0001. Expression of p16INK4A showed low sensitivity (7%, specificity (8%, positive predictive value (8%, and negative predictive value (7% for CIN I. Sensitivity, specificity, positive predictive value, and negative predictive value of p16INK4A were 78%, 61%, 30%, and 93% for CIN II/CIN III, and 100%, 75%, 61%, and 100% for squamous cell carcinoma, respectively.Results of this study suggest that p16INK4A protein may be a sensitive biomarker for CIN II/CIN III lesions and invasive squamous cell carcinoma of the uterine cervix.

  7. 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.

  8. Inhibition of Pancreatic Intraepithelial Neoplasia Progression to Carcinoma by Nitric Oxide-Releasing Aspirin in p48Cre/+-LSL-KrasG12D/+ Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2012-09-01

    Full Text Available Nitric oxide-releasing aspirin (NO-aspirin represents a novel class of promising chemopreventive agents. Unlike conventional nonsteroidal anti-inflammatory drugs, NO-aspirin seems to be free of adverse effects while retaining the beneficial activities of its parent compound. The effect of NO-aspirin on pancreatic carcinogenesis was investigated by assessing the development of precursor pancreatic lesions and adenocarcinomas in KrasG12D/+ transgenic mice that recapitulate human pancreatic cancer progression. Six-week-old male p48Cre/+-LSL-KrasG12D/+ transgenic mice (20 per group were fed diets containing 0, 1000, or 2000 ppm NO-aspirin. The development of pancreatic tumors was monitored by positron emission tomography imaging. All mice were killed at the age of 41 weeks and assessed for pancreatic intraepithelial neoplasia (PanIN and pancreatic ductal adenocarcinoma (PDAC and for molecular changes in the tumors. Our results reveal that NO-aspirin at 1000 and 2000 ppm significantly suppressed pancreatic tumor weights, PDAC incidence, and carcinoma in situ (PanIN-3 lesions. The degree of inhibition of PanIN-3 and carcinoma was more pronounced with NO-aspirin at 1000 ppm (58.8% and 48%, respectively than with 2000 ppm (47% and 20%, respectively. NO-aspirin at 1000 ppm significantly inhibited the spread of carcinoma in the pancreas (∼97%; P < .0001. Decreased expression of cyclooxygenase (COX; with ∼42% inhibition of total COX activity, inducible nitric oxide synthase, proliferating cell nuclear antigen, Bcl-2, cyclin D1, and β-catenin was observed, with induction of p21, p38, and p53 in the pancreas of NO-aspirin-treated mice. These results suggest that low-dose NO-aspirin possesses inhibitory activity against pancreatic carcinogenesis by modulating multiple molecular targets.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  11. Estimates of the timing of reductions in genital warts and high grade cervical intraepithelial neoplasia after onset of human papillomavirus (HPV) vaccination in the United States.

    Science.gov (United States)

    Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

    2013-08-20

    The objective of this study was to estimate the number of years after onset of a quadrivalent HPV vaccination program before notable reductions in genital warts and cervical intraepithelial neoplasia (CIN) will occur in teenagers and young adults in the United States. We applied a previously published model of HPV vaccination in the United States and focused on the timing of reductions in genital warts among both sexes and reductions in CIN 2/3 among females. Using different coverage scenarios, the lowest being consistent with current 3-dose coverage in the United States, we estimated the number of years before reductions of 10%, 25%, and 50% would be observed after onset of an HPV vaccination program for ages 12-26 years. The model suggested female-only HPV vaccination in the intermediate coverage scenario will result in a 10% reduction in genital warts within 2-4 years for females aged 15-19 years and a 10% reduction in CIN 2/3 among females aged 20-29 years within 7-11 years. Coverage had a major impact on when reductions would be observed. For example, in the higher coverage scenario a 25% reduction in CIN2/3 would be observed with 8 years compared with 15 years in the lower coverage scenario. Our model provides estimates of the potential timing and magnitude of the impact of HPV vaccination on genital warts and CIN 2/3 at the population level in the United States. Notable, population-level impacts of HPV vaccination on genital warts and CIN 2/3 can occur within a few years after onset of vaccination, particularly among younger age groups. Our results are generally consistent with early reports of declines in genital warts among youth. Published by Elsevier Ltd.

  12. 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...

  13. 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

    Directory of Open Access Journals (Sweden)

    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

  14. Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Gandra S

    2015-01-01

    Full Text Available Sumanth Gandra, Aline Azar, Mireya WessolosskyDivision of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA, USABackground: Although anal high-risk human papillomavirus (HR-HPV infection and anal cytological abnormalities are highly prevalent among human immunodeficiency virus (HIV-infected men who have sex with men (MSM, there are insufficient data on these abnormalities among HIV-infected heterosexual men (HSM and women. In this study, we evaluated the prevalence of anal HR-HPV, cytological abnormalities, and performance of these screening tests in detecting high-grade anal intraepithelial neoplasia (AIN2+ among our cohort of HIV-infected MSM and non-MSM (HSM and women.Methods: A single-center, retrospective cohort study was conducted with HIV-infected individuals who underwent anal cancer screening with anal cytology and HR-HPV testing from January 2011 to January 31, 2013.Results: Screening of 221 HIV-infected individuals for both HR-HPV and anal cytology showed the presence of HR-HPV in 54% (abnormal anal cytology 48% of MSM, 28% (abnormal anal cytology 28% of HSM, and 27% (abnormal anal cytology 34% of women. Among 117 (53% individuals with abnormal results (HR-HPV-positive and/or cytology was atypical squamous cells of undetermined significance or above, 67 underwent high resolution anoscopy. Of these 67 individuals, 22 individuals had AIN2+ (17 MSM, four women, and one HSM. HR-HPV correlated better with AIN2+ than with anal cytology on biopsy in both MSM (r=0.29 versus r=0.10; P=0.05 versus P=0.49 and non-MSM (r=0.36 versus r=-0.34; P=0.08 versus P=0.09.Conclusion: Given the presence of AIN2+ in screened HIV-infected HSM and women, routine anal cancer screening in all HIV-infected individuals should be considered. HR-HPV merits further evaluation for anal cancer screening among non-MSM.Keywords: human immunodeficiency virus, anal human papillomavirus, heterosexual men, women, anal cancer

  15. The detection of hTERC amplification using fluorescence in situ hybridization in the diagnosis and prognosis of cervical intraepithelial neoplasia: a case control study

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    Yin Geping

    2012-08-01

    Full Text Available Abstract Background Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN and cervical cancer are Thinprep cytology test (TCT and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients’ prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC in the diagnosis and prognosis of CIN. Methods The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11 or radical surgery (n = 14. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH, and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. Results The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% ± 4.6% and 44.4% (12/27 respectively in patients with CIN I; 16.0% ± 14.4% and 85.1% (46/54 in patients with CIN II/III; 19.7% ± 13.3% and 88.3% (15 /17 in patients with carcinoma in situ; 47.0% ± 25.2% and 100% (28/28in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P Conclusion The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Immunohistochemical characteristic of expression levels of Kі-67, p16INK4a, HPV16 in cervical intraepithelial neoplasia and cervical cancer

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    V. A. Tumanskiy

    2017-08-01

    Full Text Available Squamous cervical cancer (SCC is a common tumor in women, which is preceded by the series of pathological processes, among which the key role is played by cervical intraepithelial neoplasia (CIN. Aim. To study the characteristics of immunohistochemical (IHC expression of Ki-67, p16INK4a, HPV16 in squamous cervical epithelium (SCE with dysplastic changes of varying degree (CIN I–III and also in the tumor cells of SCC. Materials and methods. Pathohistological and IHC studies of uterine cervix biopsies from 53 patients (the age ranged from 18 to 45 years were performed. Results. It was found that SCE with CIN I is characterized by the low Ki-67 expression level (Me = 17.87 % (13.76, 22.44 and the extremely low p16INK4a expression level (Me = 0.00 CUOD (0.00; 29.64. The proportion of HPV16-positive patients with CIN I is 27.27 %. CIN II is characterized by the average proliferation level in SCE (Me = 44.96 % (34.91, 55.41 and the moderate p16INK4a expression level (Me = 75.71 CUOD (51.24, 82, 41. The proportion of HPV16-positive patients with CIN II is 71.43 %. CIN III is characterized by the high proliferation level (Me = 74.62 % (68.50, 84.67 and by the high p16INK4a expression level of in SCE (Me = 117.47 CUOD (95.38, 123, 93; the proportion of HPV16-positive patients with CIN III is 77.78%. In all the patients with SСС, nuclear and cytoplasmic expression of HPV16 was detected in the tumor cells. High expression levels of Ki-67 and p16INK4a were detected in the tumor cells. There are direct correlations between the expression levels of Ki-67, p16INK4a, HPV16 and CIN degree. Conclusions. These data indicate that the expression levels of Ki-67, p16INK4a and HPV16 increase with the increasing of CIN grade. The absence of statistically significant differences between the expression levels of Ki-67, p16INK4a and HPV16 in CIN III and the same levels in the tumor cells of SCC indicates that these markers cannot be used for differential diagnosis

  18. A Non–Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing

    Science.gov (United States)

    Cremer, Miriam; Paul, Proma; Bergman, Katie; Haas, Michael; Maza, Mauricio; Zevallos, Albert; Ossandon, Miguel; Garai, Jillian D; Winkler, Jennifer L

    2017-01-01

    ABSTRACT Background: Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low- and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs. Methods: A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy. Results: Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the

  19. 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

  20. A Non-Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing.

    Science.gov (United States)

    Cremer, Miriam; Paul, Proma; Bergman, Katie; Haas, Michael; Maza, Mauricio; Zevallos, Albert; Ossandon, Miguel; Garai, Jillian D; Winkler, Jennifer L

    2017-03-24

    Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low- and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs. A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy. Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the adapted CryoPen achieved the target depth

  1. Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands.

    Science.gov (United States)

    Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Cahh Daemen, Toos; Postma, Maarten J

    2016-12-07

    In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer.

    Science.gov (United States)

    Tenjimbayashi, Yuri; Onuki, Mamiko; Hirose, Yusuke; Mori, Seiichiro; Ishii, Yoshiyuki; Takeuchi, Takamasa; Tasaka, Nobutaka; Satoh, Toyomi; Morisada, Tohru; Iwata, Takashi; Miyamoto, Shingo; Matsumoto, Koji; Sekizawa, Akihiko; Kukimoto, Iwao

    2017-01-01

    Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences. The entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins. Among 52 isolates of HPV52 (CIN1, n  = 20; CIN2/3, n  = 21; ICC, n  = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n  = 21; CIN2/3, n  = 19; ICC, n  = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed

  3. Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia.

    Science.gov (United States)

    Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Paiva, Carlos Eduardo; Barroso, Eliane Marçon; Camargos, Mayara Goulart de; Tsunoda, Audrey Tieko; Longatto-Filho, Adhemar; Paiva, Bianca Sakamoto Ribeiro

    2017-01-01

    To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to the Portuguese language. A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term "pelvic area". The question CD5, "I worry about spreading the infection", was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia. Traduzir e adaptar o instrumento Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD), para a língua portuguesa. Estudo descritivo, transversal, com metodologia de tradução e adaptação cultural de instrumento de avaliação, realizado por meio de diretrizes internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do Brasil

  4. Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

    Science.gov (United States)

    He, Ping; Yang, Jong Won; Yang, Vincent W; Bialkowska, Agnieszka B

    2018-04-01

    Activating mutations in KRAS are detected in most pancreatic ductal adenocarcinomas (PDACs). Expression of an activated form of KRAS (KrasG12D) in pancreata of mice is sufficient to induce formation of pancreatic intraepithelial neoplasia (PanINs)-a precursor of PDAC. Pancreatitis increases formation of PanINs in mice that express KrasG12D by promoting acinar-to-ductal metaplasia (ADM). We investigated the role of the transcription factor Krüppel-like factor 5 (KLF5) in ADM and KRAS-mediated formation of PanINs. We performed studies in adult mice with conditional disruption of Klf5 (Klf5 fl/fl ) and/or expression of Kras G12D (LSL-Kras G12D ) via Cre ERTM recombinase regulated by an acinar cell-specific promoter (Ptf1a). Activation of Kras G12D and loss of KLF5 was achieved by administration of tamoxifen. Pancreatitis was induced in mice by administration of cerulein; pancreatic tissues were collected, analyzed by histology and immunohistochemistry, and transcriptomes were compared between mice that did or did not express KLF5. We performed immunohistochemical analyses of human tissue microarrays, comparing levels of KLF5 among 96 human samples of PDAC. UN-KC-6141 cells (pancreatic cancer cells derived from Pdx1-Cre;LSL-Kras G12D mice) were incubated with inhibitors of different kinases and analyzed in proliferation assays and by immunoblots. Expression of KLF5 was knocked down with small hairpin RNAs or CRISPR/Cas9 strategies; cells were analyzed in proliferation and gene expression assays, and compared with cells expressing control vectors. Cells were subcutaneously injected into flanks of syngeneic mice and tumor growth was assessed. Of the 96 PDAC samples analyzed, 73% were positive for KLF5 (defined as nuclear staining in more than 5% of tumor cells). Pancreata from Ptf1a-Cre ERTM ;LSL-Kras G12D mice contained ADM and PanIN lesions, which contained high levels of nuclear KLF5 within these structures. In contrast, Ptf1a-Cre ERTM ;LSL-Kras G12D ;Klf5 fl

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

    Science.gov (United States)

    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.

  6. Morphological features of basal membrane of stratified squamous epithelium and underlying stroma in cervical intraepithelial neoplasias and cancer of the uterine cervix

    Directory of Open Access Journals (Sweden)

    Oksana M. Pliten

    2015-06-01

    Kharkiv National Medical University   Abstract. The article presents the morphological features of the basal membrane of stratified squamous epithelium and underlying stroma in cervical intraepithelial neoplasias and cancer of the uterine cervix which were investigated by routine histological, histochemical and immunohistochemical methods. The present study indicated that as stages of carcinogenesis progress changes in the stromal-vascular component and in the basal membrane of the epithelium occur that has an important role in the differential diagnosis of the stages of carcinogenesis of the uterine cervix. Key words: uterine cervix, cervical intraepithelial neoplasias, cancer, stratified squamous epithelium, basal membrane, stroma, morphology.   Резюме. У роботі розглянуті морфологічні особливості базальної мембрани багатошарового плоского епітелію і підлягаючої строми при цервікальних інтраепітеліальних неоплазіях та раку шийки матки, які були досліджені за допомогою рутинних гістологічних, гістохімічних і імуногістохімічних методів. Дослідження показало, що у міру поважчання стадії канцерогенезу відбуваються зміни стромально-судинного компоненту і базальної мембрани епітелію. Виявлені зміни мають важливу роль у диференціальній діагностиці стадій канцерогенезу у шийці матки. Ключові слова: шийка матки, цервікальні інтраепітеліальні неоплазії, рак, багатошаровий плоский епітелії, базальна

  7. 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...

  8. Associação entre a contagem de linfócitos T CD4+ e a gravidade da neoplasia intra-epitelial cervical diagnosticada pela histopatologia em mulheres infectadas pelo HIV Association between CD4+ T-cell count and intraepithelial cervical neoplasia diagnosed by histopathology in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Juliana Barroso Zimmermmann

    2006-06-01

    Full Text Available OBJETIVO: avaliar a associação entre a contagem de linfócitos T CD4+ e a gravidade da neoplasia intra-epitelial cervical em pacientes HIV positivas. MÉTODOS: estudo transversal no qual foram incluídas 87 pacientes infectadas pelo HIV, confirmado por testes sorológicos prévios. Todas eram portadoras do HPV cervical, diagnosticado por meio da reação em cadeia da polimerase. Foram realizados anamnese, exame físico e colposcopia de todas em pacientes. A biópsia do colo uterino foi realizada quando indicada pelo exame colposcópico. Os resultados histopatológicos foram classificados com neoplasia intra-epitelial de baixo grau (NIC I ou de alto grau (NIC II e II. A associação entre a contagem de linfócitos T CD4+ e a gravidade da lesão foi verificada por meio da comparação de médias utilizando a análise da variância (ANOVA. RESULTADOS: entre as 60 pacientes biopsiadas foram encontrados 24 casos (40,0% com NIC I, oito (13,3% NIC II, três (5% NIC III, 14 (23,3% pacientes somente com cervicite crônica e 11 (18,3% apresentando efeito citopático produzido pelo HPV, mas sem perda da polaridade celular. Isso equivale a 35 mulheres com lesão intra-epitelial de baixo grau (NIC I + HPV (58,3% e 11 (18,3% com lesão intra-epitelial de alto grau (NIC II + NIC III. A associação entre a média da contagem de linfócitos T CD4+ e a gravidade da lesão intra-epitelial cervical não foi significativa (p=0,901. CONCLUSÕES: não houve associação entre a contagem de linfócitos T CD4+ e a gravidade da lesão intra-epitelial do colo uterino, diagnosticada pelo exame histopatológico.PURPOSE: to evaluate association between CD4+ cell count and cervical intraepithelial lesion severity in HIV-infected women. METHODS: cross-sectional study of 87 HIV-infected patients which were confirmed by previous serologic examinations. All had cervical HPV diagnosed by polymerase chain reaction (PCR. All patients underwent anamnesis, physical examinations and

  9. 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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

    DEFF Research Database (Denmark)

    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...

  11. The Application of Classification and Regression Trees for the Triage of Women for Referral to Colposcopy and the Estimation of Risk for Cervical Intraepithelial Neoplasia: A Study Based on 1625 Cases with Incomplete Data from Molecular Tests

    Directory of Open Access Journals (Sweden)

    Abraham Pouliakis

    2015-01-01

    Full Text Available Objective. Nowadays numerous ancillary techniques detecting HPV DNA and mRNA compete with cytology; however no perfect test exists; in this study we evaluated classification and regression trees (CARTs for the production of triage rules and estimate the risk for cervical intraepithelial neoplasia (CIN in cases with ASCUS+ in cytology. Study Design. We used 1625 cases. In contrast to other approaches we used missing data to increase the data volume, obtain more accurate results, and simulate real conditions in the everyday practice of gynecologic clinics and laboratories. The proposed CART was based on the cytological result, HPV DNA typing, HPV mRNA detection based on NASBA and flow cytometry, p16 immunocytochemical expression, and finally age and parous status. Results. Algorithms useful for the triage of women were produced; gynecologists could apply these in conjunction with available examination results and conclude to an estimation of the risk for a woman to harbor CIN expressed as a probability. Conclusions. The most important test was the cytological examination; however the CART handled cases with inadequate cytological outcome and increased the diagnostic accuracy by exploiting the results of ancillary techniques even if there were inadequate missing data. The CART performance was better than any other single test involved in this study.

  12. Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation

    International Nuclear Information System (INIS)

    Silva, Sonali S. de; Payne, Geoffrey S.; Morgan, Veronica A.; Ind, Thomas E.J.; Shepherd, John H.; Barton, Desmond P.J.; Souza, Nandita M. de

    2009-01-01

    To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR=1,500 ms, TE=135 ms). tCho, 2 ppm and -CH 2 lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. 1 H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p=0.03) and 2 ppm (p=0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH 2 lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH 2 lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer. (orig.)

  13. 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.

  14. The Application of Classification and Regression Trees for the Triage of Women for Referral to Colposcopy and the Estimation of Risk for Cervical Intraepithelial Neoplasia: A Study Based on 1625 Cases with Incomplete Data from Molecular Tests.

    Science.gov (United States)

    Pouliakis, Abraham; Karakitsou, Efrossyni; Chrelias, Charalampos; Pappas, Asimakis; Panayiotides, Ioannis; Valasoulis, George; Kyrgiou, Maria; Paraskevaidis, Evangelos; Karakitsos, Petros

    2015-01-01

    Nowadays numerous ancillary techniques detecting HPV DNA and mRNA compete with cytology; however no perfect test exists; in this study we evaluated classification and regression trees (CARTs) for the production of triage rules and estimate the risk for cervical intraepithelial neoplasia (CIN) in cases with ASCUS+ in cytology. We used 1625 cases. In contrast to other approaches we used missing data to increase the data volume, obtain more accurate results, and simulate real conditions in the everyday practice of gynecologic clinics and laboratories. The proposed CART was based on the cytological result, HPV DNA typing, HPV mRNA detection based on NASBA and flow cytometry, p16 immunocytochemical expression, and finally age and parous status. Algorithms useful for the triage of women were produced; gynecologists could apply these in conjunction with available examination results and conclude to an estimation of the risk for a woman to harbor CIN expressed as a probability. The most important test was the cytological examination; however the CART handled cases with inadequate cytological outcome and increased the diagnostic accuracy by exploiting the results of ancillary techniques even if there were inadequate missing data. The CART performance was better than any other single test involved in this study.

  15. 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.

    Science.gov (United States)

    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.

  16. 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.

  17. Human papillomavirus 16 E2-, E6- and E7-specific T-cell responses in children and their mothers who developed incident cervical intraepithelial neoplasia during a 14-year follow-up of the Finnish Family HPV cohort.

    Science.gov (United States)

    Koskimaa, Hanna-Mari; Paaso, Anna E; Welters, Marij J P; Grénman, Seija E; Syrjänen, Kari J; van der Burg, Sjoerd H; Syrjänen, Stina M

    2014-02-13

    Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. Given the lack of any studies on HPV-specific immune responses in children, we conducted HPV16-specific cell-mediated immune (CMI) monitoring of the mother-child pairs with known oral and genital HPV follow-up (FU) data since the delivery. In the Finnish Family HPV Study, 10 out of 331 mothers developed incident cervical intraepithelial neoplasia (CIN) during their 14-year FU. Our hypothesis according to the common dogma is that there is no HPV16 specific immune response in offspring of the CIN mother as she/he has not started the sexual life yet. We used overlapping 30-35 mer peptides covering the entire HPV16 E2, E6 and E7 protein sequences. Assays for lymphocyte proliferation capacity, cytokine production and HPV16-specific Foxp3 + CD25 + CD4+ regulatory T-cells were performed. HPV16-specific proliferative T-cell responses were broader in children than in their mothers. Nine of 10 children had responses against both E2 peptide pools compared to only 4 of the 10 mothers. Six of the 10 children and only 2 mothers displayed reactivity to E6 and/or E7. The cytokine levels of IL-2 (p = 0.023) and IL-5 (p = 0.028) induced by all peptide pools, were also higher among children than their mothers. The children of the mothers with incident CIN3 had significantly higher IFN-γ (p = 0.032) and TNF-α (p = 0.008) levels than other children. Our study is the first to show that also children could have HPV-specific immunity. These data indicate that the children have circulating HPV16-specific memory T-cells which might have been induced by previous HPV16 exposure or ongoing HPV 16 infection.

  18. Lesões induzidas por papilomavírus humano em parceiros de mulheres com neoplasia intra-epitelial do trato genital inferior Papillomavírus-induced lesion in partners of womem with intraepithelial neoplasia of the lower genital tract

    Directory of Open Access Journals (Sweden)

    Júlio César Teixeira

    1999-01-01

    Full Text Available RESUMO Objetivos: pesquisar a presença de lesões induzidas por papilomavírus (HPV e os fatores associados em parceiros de mulheres com neoplasia intra-epitelial genital. Métodos: foram avaliados 337 homens por meio de citologia uretral, peniscopia e biópsia, quando necessário. Analisou-se a presença de lesão induzida por HPV correlacionando-a com a idade, escolaridade, tabagismo, estabilidade conjugal, início da atividade sexual, número de parceiras, antecedente de doença sexualmente transmissível (DST, postectomia, imagens peniscópicas e grau das lesões nas mulheres. Resultados: a peniscopia foi positiva em 144 homens (42,7% e 105 (31,2% apresentaram lesões induzidas por HPV. Somente o tabagismo, a estabilidade conjugal menor ou igual a seis meses e o antecedente de mais de uma parceira sexual estiveram associados com a presença de lesão induzida por HPV (pPurpose: to evaluate risk factors and papillomavirus (HPV associated lesions in male partners of women with genital intraepithelial neoplasia. Patients and Methods: three hundred and thirty-seven men were evaluated by urethral cytology, peniscopy, and biopsy, if necessary. We analyzed the results and the relations to age, educational level, smoking, contact time with the present partner, age at first intercourse, number of partners, previous sexually transmitted diseases (STD, circumcision, peniscopic findings, and female lesion grade. Results: peniscopy was positive in 144 (42,7% and HPV infection was diagnosed in 105 (31,2%. Smoking, contact time with the present partner up to 6 months, and more than one previous sexual partner were associated with HPV lesions (p<0,05. The urethral cytology was suspect in 4,2% and smoking, positive peniscopy or biopsy and partners of women with high-grade lesion (p<0,05 were associated with the diagnosis. 72.1% of 229 biopsies were positive, independently of the peniscopic findings and women's lesion grade. Conclusions: HPV infection was

  19. 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.

  20. Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice: effects of alcohol and caffeine Neoplasia pancreática intraepithelial e adenocarcinoma ductal induzidos pelo DMBA em camundongos: efeitos do álcool e da cafeína

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    Luiz Roberto Wendt

    2007-06-01

    Full Text Available PURPOSE: To evaluate the effects of alcohol and caffeine in a pancreatic carcinogenesis mouse model induced by 7,12-dimethylbenzantracene (DMBA, according to the PanIN classification system. METHODS: 120 male, Mus musculus, CF-1 mice were divided into four groups. Animals received either water or caffeine or alcohol or alcohol + caffeine in their drinking water. In all animals, 1 mg of DMBA was implanted into the head of the pancreas. After 30 days, euthanasia was performed; excised pancreata were then fixed in formalin, stained with hematoxylin-eosin and categorized as follows: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 or adenocarcinoma. RESULTS: PanIN lesions were verified in all groups. Adenocarcinoma was detected in 15% of animals in the caffeine group, 16.6% in the water group, 23.8% in the alcohol + caffeine group and 52.9% in the alcohol group (POBJETIVO: Avaliar os efeitos do álcool e da cafeína na carcinogênese pancreática induzida pelo 7,12-dimetilbenzantraceno (DMBA em camundongos, descrevendo as lesões de acordo com a classificação das neoplasias pacreáticas intraepiteliais (PanIN. MÉTODOS: 120 camundogos machos, Mus musculus, CF-1 foram divididos em quatro grupos. Animais receberam água ou cafeína ou álcool ou álcool + cafeína para beber. Em todos animais, 1 mg de DMBA foi implantado na cabeça do pâncreas. Após 30 dias, eutanásia foi realizada, o pâncreas foi removido, fixado em formalina e corado com hematoxilina e eosina sendo classificado em: ductos normais, hiperplasia reativa, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 ou adenocarcinoma. RESULTADOS: Neoplasias pancreáticas intraepiteliais foram encontradas em todos grupos. Adenocarcinoma foi detectado em 15% dos animais do grupo cafeína, 16,6% do grupo água, 23,8% do grupo álcool + cafeína e 52,9% do grupo álcool (P<0,05. CONCLUSÕES: O modelo experimental de carcinogênese pancreática em camundongos utilizando DMBA induz

  1. Plasma proteome analysis of cervical intraepithelial neoplasia

    Indian Academy of Sciences (India)

    ... Malaysia and University of Malaya Centre For Proteomics Research (UMCPR), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; Department of Clinical Oral Biology, Faculty of Dentistry; Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; Department of Obstetrics and Gynecology; Universiti Kebangsaan ...

  2. 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.

    Science.gov (United States)

    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

  3. 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

    Directory of Open Access Journals (Sweden)

    Railda Fraga Costa

    2011-01-01

    Full Text Available OBJETIVOS: Determinar a prevalência de lesões intraepiteliais de baixo e alto grau, em mulheres com diagnóstico colpocitológico de atipias de significado indeterminado no Município de Maceió, Alagoas. Conhecer a influência da idade e dos agentes etiológicos para doenças sexualmente transmissíveis sobre o risco de desenvolvimento das lesões intraepiteliais de baixo e alto grau. MÉTODOS: Estudo transversal de prevalência em um serviço público de referência para neoplasias cervicais. Foram estudados 253 prontuários de mulheres com diagnóstico de atipias de significado indeterminado, no ano de 2007. RESULTADOS: A prevalência de lesões intraepiteliais foi a de 23,7%, sendo 26,7% de baixo grau e 73,3% de alto grau. CONCLUSÕES: A prevalência de lesões intraepiteliais de alto grau em mulheres com diagnóstico colpocitológico de atipias de significado indeterminado (ASCUS foi de 23,7%, o aumento do risco foi diretamente proporcional ao da idade e houve maior prevalência de lesão intraepitelial de baixo grau,associada à infecção pelo Papilomavirus humano.OBJETIVOS: Determinar la prevalencia de lesiones intraepiteliales de bajo y alto grado, en mujeres con diagnóstico colpocitológico de atipias de significado indeterminado en el Municipio de Maceió, Alagoas. Conocer la influencia de la edad y de los agentes etiológicos para enfermedades sexualmente transmisibles sobre el riesgo de desarrollo de las lesiones intraepiteliales de bajo y alto grado. MÉTODOS: Se trata de un estudio transversal de prevalencia realizado en un servicio público de referencia para neoplasias cervicales. Fueron estudiadas 253 historias clínicas de mujeres con diagnóstico de atipias de significado indeterminado, en el año 2007. RESULTADOS: La prevalencia de lesiones intraepiteliales fue del 23,7%, siendo 26,7% de bajo grado y 73,3% de alto grado. CONCLUSIONES: La prevalencia de lesiones intraepiteliales de alto grado en mujeres con diagn

  4. Prevalence of cervical intraepithelial neoplasia and invasive carcinoma based on cytological screening in the region of Campinas, São Paulo, Brazil Prevalência da neoplasia intra-epitelial cervical e do carcinoma invasivo com base no rastreamento citológico na região de Campinas, São Paulo, Brasil

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    Maria Gabriela L. d'Ottaviano-Morelli

    2004-02-01

    Full Text Available This study aimed to estimate and analyze the prevalence of cervical intraepithelial neoplasia (CIN and invasive cervical carcinoma based on cytological diagnosis. The study included 120,635 women undergoing cytological exams in public health services in the region of Campinas, São Paulo State, Brazil, between September 1998 and March 1999. Prevalence rates per 100,000 women were: 354 for CIN I; 255 for CIN II; 141 for CIN III; and 24 for invasive carcinoma. As age increased, prevalence rates and prevalence ratios decreased for CIN grades I and II and increased for CIN III until the 50-54 age group, decreasing thereafter The prevalence rate of invasive carcinoma increased with age. The prevalence pattern of CIN II was distinct from that of CIN III, but similar to that of CIN I. This would not have been observed if the Bethesda System had been used for cytological diagnosis. Mean age at time of CIN II diagnosis was about 10 years less than for CIN III diagnosis. Therefore, a high-grade lesion diagnosed in a young woman according to the Bethesda System would probably be a CIN II, whereas in an older woman it would probably be a CIN III.O objetivo deste estudo foi estimar e analisar a prevalência das neoplasias intra-epiteliais cervicais (NIC e do carcinoma invasivo do colo uterino, com base no diagnóstico citológico. Foram incluídas 120.635 mulheres que realizaram o exame citológico, entre setembro de 1998 a março de 1999, nos serviços públicos de saúde da região de Campinas, Brasil. As prevalências por 100 mil mulheres foram: 354 para NIC I; 255 para NIC II; 141 para NIC III e 24 de carcinoma invasivo. À medida que a idade aumentou, as prevalências e razões de prevalência diminuíram para NIC I e NIC II, e aumentaram para NIC III até 50-54 anos, decrescendo após. A prevalência do carcinoma invasivo aumentou com a idade. O padrão da prevalência da NIC II é distinto do padrão da NIC III e semelhante ao da NIC I, o que n

  5. Desempenho do exame colpocitológico com revisão por diferentes observadores e da captura híbrida II no diagnóstico da neoplasia intra-epitelial cervical graus 2 e 3 Performance of cervical cytology with review by different observers and hybrid capture II in the diagnosis of cervical intraepithelial neoplasia grades 2 and 3

    Directory of Open Access Journals (Sweden)

    André Luís Ferreira Santos

    2003-08-01

    Full Text Available Para avaliar o desempenho da colpocitologia (CO de encaminhamento e daquela coletada no serviço de referência, com revisão por diferentes técnicas e observadores, e da captura híbrida II (CH II no diagnóstico da neoplasia intra-epitelial cervical (NIC de alto grau, foram incluídas 105 mulheres atendidas entre agosto de 2000 e junho de 2001 por atipias pré-neoplásicas na CO. Todas foram submetidas à coleta de nova CO e CH II para detecção do DNA-HPV. Foi realizada biópsia cervical em 91, sendo o diagnóstico histológico considerado padrão ouro. Foram descritas a sensibilidade, especificidade e razão de verossimilhança positiva (RVP dos métodos propedêuticos com intervalo de confiança de 95% (IC95%. A sensibilidade e especificidade da CO de encaminhamento foi de 57% e 82% para o diagnóstico de NIC 2 e 3, e a RVP de 3,2 (IC95%: 1,5-6,8. A CO do serviço mostrou uma sensibilidade e especificidade 79% e 84%, respectivamente e RVP de 5,0 (IC95%: 2,5-10,0. A sensibilidade (86%, especificidade (80% e RVP (4,3 foram semelhantes com a revisão lenta realizada pelo segundo observador, havendo uma queda significativa da sensibilidade (64% à revisão rápida pelo terceiro observador. A CH II mostrou alta sensibilidade (100%, baixa especificidade (43% e baixa RVP (1,7, IC95%: 1,4-2,2.To evaluate the performance of initial cervical cytology and that collected at the reference service with a review conducted by different observers and techniques, as well as hybrid capture II, in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN, 105 women attended from August 2000 to June 2001 for preneoplastic atypia upon cervical cytology were included. A new cervical cytology and hybrid capture II for DNA-HPV were conducted in all the patients. Cervical biopsies were taken in 91 women. Performance of the investigative procedures was described by estimating the sensitivity, specificity, and positive likelihood ratio (PLR, with a 95

  6. Presença da Proteína p53 como Prognóstico de Recidiva/Progressão de Neoplasia Intra-epitelial Vulvar III p53 Protein Overexpression as a Prognostic Marker for Vulvar Intraepithelial Neoplasia III Recurrence/Progression

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    Isabel Cristina Chulvis do Val Guimarães

    2002-01-01

    Full Text Available Objetivo: avaliar o valor da presença da proteína p53 nos casos de recidiva/progressão da neoplasia intra-epitelial vulvar (VIN III. Métodos: foram selecionadas 20 pacientes com VIN III indiferenciada, seguidas semestralmente por período de até quatro anos, divididas em dois grupos: quatorze sem e seis com recidiva/progressão da lesão. Os casos de recidiva/progressão foram distribuídos da seguinte forma: em três pacientes a recidiva ocorreu uma única vez, em duas, houve dupla recorrência e apenas uma evoluiu para carcinoma escamoso. Em ambos os grupos foram avaliados o sítio vulvar acometido e a presença da proteína p53 com análise do padrão de marcação imunohistoquímica. Estudo semelhante foi realizado nos casos de recidiva/progressão além da análise do intervalo de tempo para o surgimento de recidiva/progressão. Resultados: observou-se recidiva da VIN III em 25% dos casos e, em 5%, progressão para carcinoma. O tempo médio de recidiva foi de 24,5 meses. A localização multifocal da lesão primária foi a mais freqüente (50% em ambos os grupos. Na maioria dos casos (87,5%, a recidiva/progressão ocorreu na mesma localização da lesão vulvar primária. A presença da proteína p53 mostrou-se positiva em 50% das lesões primárias de VIN III e em 75% dos casos de recidiva/progressão. Conclusões: a presença da proteína p53 parece desempenhar papel importante na gênese e na predição do curso clínico das VIN III. As recidivas/progressão das VIN III tendem a ocorrer na mesma área da doença inicial, sugerindo a presença de campo molecular alterado.Purpose: to evaluate p53 overexpression value in vulvar intraepithelial neoplasia (VIN III recurrence/progression. Methods: twenty patients with undifferentiated VIN III were selected and followed up every six months for four years and divided into two groups: fourteen without and six with recurrence/progression lesion. The recurrence/progression cases were

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Human papilloma virus identification in breast cancer patients with previous cervical neoplasia

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2016-01-01

    Full Text Available Purpose: Women with human papilloma virus (HPV associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i identify high risk for cancer HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii determine if these HPVs were biologically active.Methods: A range of polymerase chain reaction (PCR and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. Results: The same high risk HPV types were identified in both the cervical and breast specimens in 13 (46% of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001. Conclusions: These findings indicate that high risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of 2 similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  9. Inspeção visual do colo uterino após aplicação de ácido acético no rastreamento das neoplasias intra-epiteliais e lesões induzidas por HPV Cervical visual inspection after application of acetic acid in screening intraepithelial neoplasia and HPV-induced lesions

    Directory of Open Access Journals (Sweden)

    Maria Rachel Aguiar Cordeiro

    2005-02-01

    Full Text Available OBJETIVO: estimar a validade da inspeção visual após aplicação de ácido acético (IVA no rastreamento das neoplasias intra-epiteliais cervicais (NIC e lesões induzidas por HPV, comparando seu desempenho com o da colpocitologia e da colposcopia. MÉTODOS: estudo de validação de teste diagnóstico realizado em 893 mulheres de 18 a 65 anos, rastreadas simultaneamente com colpocitologia, IVA e colposcopia, em unidade de saúde pública de Recife, PE. A IVA foi realizada por embrocação do colo com ácido acético a 5% e observação a olho nu, com auxílio de foco clínico comum. Considerou-se como positividade o achado de qualquer lesão aceto-branca no colo. O padrão-ouro foi o histopatológico de biópsia cervical, realizado sempre que qualquer um dos três testes resultasse anormal. Foram estimados e comparados os indicadores de validade de cada teste, com os respectivos intervalos de confiança a 95%. A concordância entre os resultados dos testes foi avaliada pelo coeficiente kappa (k. RESULTADOS: das 303 mulheres biopsiadas, o estudo histopatológico foi anormal em 24. Deste total, a IVA foi positiva em 22, conferindo-lhe sensibilidade estimada de 91,7%, especificidade de 68,9%, valor preditivo positivo de 7,5% e valor preditivo negativo de 99,7%. Comparando-se os intervalos de confiança a 95%, a IVA mostrou maior sensibilidade que a colpocitologia, mas com menores especificidade e valor preditivo positivo. Houve fraca concordância entre os resultados da IVA e da colpocitologia (k=0,02 e excelente concordância com os da colposcopia (k=0,93. CONCLUSÃO: a IVA foi muito mais sensível que a colpocitologia no rastreamento das NIC e lesões HPV-induzidas e teve o mesmo desempenho da colposcopia. Sua baixa especificidade foi responsável por um elevado número de resultados falso-positivos.PURPOSE: to estimate the validity of visual inspection of cervical intraepithelial neoplasia (CIN and HPV-induced lesion screening, after acetic

  10. Relação entre diagnóstico citopatológico de neoplasia intra-epitelial cervical e índices de células CD4+ e de carga viral em pacientes HIV-soropositivas Association of cervical intraepithelial neoplasia with CD4 T cell counts and viral load in HIV-infected women

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    Raquel Autran Coelho

    2004-03-01

    -RNA viral load in HIV-positive patients. METHODS: one hundred and fifteen HIV patients were evaluated retrospectively in the present study, during the period from January 2002 to April 2003, at a university hospital. Eighty-three patients presented cervical intraepithelial neoplasia (CIN in Pap smear, in comparison with thirty-two with no lesions. Patients were divided into three groups, according to CD4 counts: CD4 more than 500 cells/mm³, between 200 and 500 cells/mm³, and less than 200 cells/mm³, and other three groups, according to HIV viral load: less than 10,000 HIV-RNA copies/mL, between 10,000 and 100,000 HIV-RNA copies/mL, or more than 100,000 HIV-RNA copies/mL. Correlation was investigated by the Fisher test. RESULTS: of the eighty-three patients with CIN, 73% presented CD4 counts less than 500 cells/mm³. In all CD4 groups, more than 50% of the patients presented CIN. According to the viral load, 71.7% of the patients with less than 10,000 HIV-RNA copies/mL presented CIN I, compared with 11.3% that showed CIN III. In the group with higher viral load (>100.000 HIV-RNA copies/mL, 61.5% showed CIN I and 30.8% presented CIN III. CONCLUSION: association between viral load and CIN was established (p=0.013, which was not observed with CD4 cell counts and CIN. Concomitant cervicovaginal infection was considered a potential confounding factor.

  11. 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

    Science.gov (United States)

    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

  12. Detection of colorectal neoplasia

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise

    2017-01-01

    Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA...... value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC....

  13. 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

  14. 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

  15. A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3).

    Science.gov (United States)

    Alvarez, Ronald D; Huh, Warner K; Bae, Sejong; Lamb, Lawrence S; Conner, Michael G; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A; Hester, Shirley; Jackson, Bradford E; Wu, T C; Trimble, Cornelia L

    2016-02-01

    The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Detecção do DNA do papilomavírus humano após excisão da zona de transformação com alça diatérmica para tratamento de neoplasia intra-epitelial cervical Human papillomavirus DNA detection after large loop excision of the transformation zone for the treatment of cervical intraepithelial neoplasia

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    Priscila Garcia Figueirêdo

    2003-02-01

    Full Text Available OBJETIVO: avaliar a presença do DNA do papilomavírus humano (HPV de alto risco oncológico antes e quatro meses após excisão da zona de transformação com alça diatérmica em mulheres com neoplasia intra-epitelial cervical (NIC. MÉTODOS: neste estudo clínico prospectivo foram incluídas 78 mulheres submetidas à excisão da zona de transformação tratadas no período de fevereiro a dezembro de 2001. Todas foram submetidas a colposcopia, citologia oncológica e captura híbrida II (CH II antes da cirurgia e após 4±1,25 meses. Para análise estatística utilizou-se o cálculo do odds ratio (OR com intervalo de confiança de 95% (IC 95%. RESULTADOS: antes da excisão, 67 (86% mulheres apresentavam CH II positiva para DNA-HPV de alto risco oncológico e destas, apenas 22 (33% mantiveram a CH II positiva quatro meses após. A detecção do DNA-HPV após o tratamento não se relacionou com a carga viral prévia, presença de doença nas margens da peça cirúrgica ou idade da mulher. Após quatro meses, a detecção do DNA-HPV associou-se significativamente com a presença de alterações citológicas (OR = 4,8; IC 95% = 1,7-13,7, porém não se relacionou com doença residual ou recidiva histológica (OR = 6,0; IC 95% = 0,8-52,3. CONCLUSÃO: após o tratamento da NIC, a detecção do DNA-HPV diminuiu significativamente porém não se observou relação com a presença de doença residual ou recidiva histológica.PURPOSE: to evaluate the detection of high oncogenic risk human papillomavirus DNA (HPV-DNA immediately before and 4±1.25 months after large loop excision of the transformation zone (LLETZ in the treatment of cervical intraepithelial neoplasia (CIN. METHODS: in this clinical prospective study, 78 patients submitted to LLETZ from February to December 2001 were enrolled. All patients were submitted to colposcopic evaluation and had Pap smear and hybrid capture II (HC II specimens collected immediately before LLETZ and four months

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

    Science.gov (United States)

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

    2016-03-15

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

  18. Short-term risk of cervical intraepithelial neoplasia grades 2 and 3 for women with normal cytology and human papillomavirus infection Riesgo a corto plazo de lesiones intraepiteliales cervicales grados 2 y 3 en mujeres con citología vaginal normal e infección por el virus del papiloma humano

    Directory of Open Access Journals (Sweden)

    Gustavo Hernández-Suárez

    2010-12-01

    Full Text Available OBJECTIVE. To assess the risk of cervical intraepithelial neoplasia grades 2, 3 or higher (CIN 2/3+ for women with normal cytology and concurrent high-risk human papillomavirus infection (HR-HPV. MATERIAL AND METHODS. We examined 2 200 women every 6 months for an average of 9 years. Cervical smears and samples for HPV DNA were obtained at each visit. Absolute risk of subsequent CIN2/CIN3+ was estimated using the Kaplan-Meier method. RESULTS. The absolute risk of CIN2/CIN3+ among HR-HPV-positive women with normal Pap smear results was 1.06% (95%CI, 0.57-2.20, 5 times higher the risk among all women with normal Pap smears (0.20%; 95%CI, 0.12-0.32 but 7 times lower than that for women with HR-HPV infection and LSIL (7.24%; 95%CI, 3.78-15.2. CONCLUSION. Short-term absolute risk of CIN2/3+ after a normal Pap smear with concurrent HR-HPV infection is low (~1%, suggesting that the HR-HPV test has limited utility in short-term clinical decision-making for women with normal cytology.OBJETIVO. Evaluar el riesgo a corto plazo de neoplasia intraepitelial cervical de alto grado (CIN2/CIN3+ en mujeres con citologí-a cervicouterina normal e infección por virus del papiloma humano de alto riesgo (HR-HPV. MATERIAL Y MÉTODOS. Cohorte prospectiva de 2200 mujeres evaluadas cada seis meses durante 9 años en promedio. En cada visita se tomó muestra cervical para extendido y detección de HPV DNA. El riesgo absoluto de CIN2/CIN3+ a la siguiente visita fue calculado utilizando el método de Kaplan-Meier. RESULTADOS. En mujeres con citologí-a normal e infección concomitante por HR-HPV el riesgo absoluto de presentar CIN2/CIN3+ fue de 1.06% (95%CI, 0.57-2.20. Este riesgo fue cinco veces mayor al observado en todas las mujeres con citologí-a normal (0.20%; 95%CI, 0.12-0.32 pero siete veces menor que el observado en mujeres con lesiones intraepiteliales escamosas de bajo grado con infección concomitante (7.24%; 95%CI, 3.78-15.2. CONCLUSIÓN. El riesgo absoluto de

  19. Vaginose bacteriana e DNA de papilomavírus humano de alto risco oncogênico em mulheres submetidas a conização com alça diatérmica para tratamento de neoplasia intra-epitelial cervical de alto grau Bacterial vaginosis and high-risk HPV-DNA in women submitted to diathermic conization for the treatment of high-grade cervical intra-epithelial neoplasia

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    Michelle Garcia Discacciati

    2004-10-01

    ção às mulheres sem VB, ainda que estatisticamente não significativa. Esta associação não foi relacionada à presença do DNA de HPV de alto risco.PURPOSE: to analyze the association between bacterial vaginosis (BV, high-risk HPV DNA, and Pap smear abnormalities in women submitted to diathermic conization for the treatment of high-grade cervical intraepithelial neoplasia (CIN 2 or 3. METHODS: a descriptive clinical study with 81 women submitted to diathermic conization for the treatment of CIN 2 or 3. Initial Pap smear was performed by the time of the biopsy and was also used to verify the presence of BV. Prior to conization, samples for the detection of high-risk HPV DNA through hybrid capture II (HC II were collected. A control visit was scheduled for four months after the conization to repeat these tests. Twenty-seven women were found to have BV and 54 were not. Statistical analysis comprised odds ratios (OR to assess the correlations between BV and HPV detection before and after diathermic conization and cytological abnormalities. All analyses were performed with a 95% confidence interval (95% CI. RESULTS: high-risk HPV DNA detection before conization was identical in both groups (89%. After conization, HPV DNA detection decreased to 26 and 18% in the groups with and without BV, respectively (OR=1.5; 95% CI 0.5 to 4.6. In addition, 41% of the women with BV and 20% without BV showed Pap smear abnormalities (OR=2.7; 95% CI 1.0 to 7.4. Regarding these 22 women with Pap smear abnormalities approximately four months after the diathermic conization, 83% of the BV group tested positive for HPV DNA compared with 50% in the group without BV (OR=5.0; IC 95% 0.5 a 52.9. CONCLUSION: women with BV presented more Pap smear abnormalities after conization when compared to the women without BV, although this was not statistically significant. This association was not related to high-risk HPV DNA.

  20. 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.

  1. Plasma proteome analysis of cervical intraepithelial neoplasia and ...

    Indian Academy of Sciences (India)

    Prakash

    cancer will contribute to an understanding of how the disease develops and progresses. ... grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel .... centrifugation at 800xg for 10 min at 4°C and kept in aliquots ..... reveals differential expression of vitamin D binding protein;.

  2. Colposcopy in diagnosis and treatment of cervical intraepithelial neoplasia (CIN)

    NARCIS (Netherlands)

    W.M. Huisman (Wouter); J.A. Wijnen (Hans)

    1987-01-01

    textabstractAIMS OF THE STUDIES 1. To investigate the diagnostic value of colposcopy under research conditions, in patients with an indication for colposcopy. (Wouter M. Huisman) 2. To investigate the possibility of accurately predicting histopathology by means of the colposcopic impression,

  3. Correlação entre o Diagnóstico Histológico da Biópsia e o da Conização por Cirurgia de Alta Freqüência por Alça (CAF no Tratamento da Neoplasia Intra-epitelial Cervical Correlation between the Histological Report of Biopsy and Conization by the Loop Electrosurgical Excision Procedure (LEEP in the Treatment of Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Cássia Raquel Teatin Juliato

    2000-03-01

    Full Text Available Objetivos: avaliar a utilização da conização por cirurgia de alta freqüência por alça (CAF na neoplasia intra-epitelial cervical (NIC, a importância do comprometimento das margens de ressecção e o seguimento das pacientes. Métodos: foram avaliadas 95 mulheres submetidas à CAF por NIC entre janeiro de 1996 e dezembro de 1997. Para análise estatística, utilizamos o coeficiente de concordância kappa e o teste de tendência de Cochran Armitage. Resultados: dos 63 casos submetidos à biópsia dirigida antes da conização, o cone por CAF apresentou lesões mais graves que a biópsia em 24 casos, sendo um caso microinvasor, e em 8 mulheres a biópsia eliminou a lesão. Entre as pacientes submetidas à conização com biópsia prévia compatível com cervicite ou NIC 1, 14/25 (56% apresentavam NIC 2 ou 3. Das 32 mulheres que não tinham biópsia prévia, 15 apresentavam NIC 2 ou 3, e quatro, carcinoma microinvasor no cone. Em relação às margens do cone, 25 casos (26% apresentaram margens endocervicais comprometidas e quanto maior o grau da lesão cervical maior a possibilidade de presença de lesão nas margens (p = 0,024. Dessas pacientes, 2 de 10 submetidas a novo procedimento apresentavam doença residual na peça cirúrgica. Entre as 70 pacientes com margens livres foram realizadas três conizações a frio e uma histerectomia e duas apresentavam doença residual na peça cirúrgica. Conclusões: a conização por CAF sem biópsia prévia depende da combinação entre o diagnóstico citológico e a experiência do colposcopista e, em princípio, deve ser reservada para os casos em que a colpocitologia e a colposcopia são concordantes e compatíveis com NIC 2 ou 3. Por outro lado, a ampliação cirúrgica pós-CAF no tratamento da NIC não é determinada exclusivamente pelo comprometimento das margens, mas sim pelo seguimento, excluindo-se os casos de microinvasão e lesões glandulares que se beneficiam com a avaliação histol

  4. Stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia: report on a Brussels' cohort

    NARCIS (Netherlands)

    Pouw, R. E.; Peters, F. P.; Sempoux, C.; Piessevaux, H.; Deprez, P. H.

    2008-01-01

    Background and study aims: The aim of this retrospective study was to assess safety and efficacy of stepwise radical endoscopic resection (SRER) in patients with Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or early cancer. Patients and methods: Patients undergoing SRER

  5. HPV infection and intraepithelial lesions from the anal region: how to diagnose?

    Directory of Open Access Journals (Sweden)

    Newton Sérgio de Carvalho

    Full Text Available In the last years, the prevalence of HPV infection in the anal region has increased, especially in some groups like homosexual and HIV-positive people. Since this infection can be associated with the development of squamous anal cancer due to its progression from HPV infection to anal intraepithelial neoplasia (AIN and finally to cancer, the screening and evaluation of these conditions are important. Anal cytology and high resolution anoscopy are good methods that are available and can be used. Although useful, these methods should be performed correctly and not indiscriminately in all patients. Patients for whom anal cytology screening is recommended are: HIV-infected patients, homosexuals, women who present with high-grade vulvar squamous intraepithelial neoplasia, vulvar cancer or cervical cancer. An abnormal anal cytology should be further evaluated with high resolution anoscopy.

  6. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region

    DEFF Research Database (Denmark)

    Castellsagué, Xavier; Ault, Kevin A; Bosch, F Xavier

    2016-01-01

    Background: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region. Methods: Women ages 15-26 and 24-45 years from 5 regions were...

  7. Germ cell neoplasia in situ (GCNIS)

    DEFF Research Database (Denmark)

    Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad

    2016-01-01

    The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagr......The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity...... and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce...

  8. Role of human immunodeficiency virus infection in the pathogenesis of human papillomavirus-associated cervical neoplasia.

    OpenAIRE

    Braun, L.

    1994-01-01

    Although many basic questions about the relationship between HIV and HPV infection remain unresolved, epidemiological studies have consistently shown a strong association between HIV infection and the development of HPV-related squamous intraepithelial neoplasia. This work indicates that HIV infection may promote the clinical manifestation of subclinical or latent HPV infection. Recent technical advances localizing virus DNA and gene products in situ will provide new avenues for investigation...

  9. 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.

    Science.gov (United States)

    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.

  10. Spectrum of ocular surface squamous neoplasia

    International Nuclear Information System (INIS)

    Babar, T.F.; Khan, M.N.; Hussain, M.; Shah, S.A.

    2007-01-01

    To describe the pattern of ocular surface squamous neoplasia (OSSN), clinical presentations, the risk factors and treatment options. The study included 36 eyes of 35 patients with biopsy-proven ocular surface neoplasia. The details of patients regarding age, gender, laterality and risk factors were entered into a specially-designed proforma. Each patient was also assessed biomicroscopically for type and complications of ocular surface neoplasia. The frequency of OSSN was 0.37 among admitted hospital patients. Among 36 cases of OSSN, squamous cell carcinoma of the conjunctiva was the most common type of OSSN seen in 63.9%, followed by carcinoma in situ of conjunctiva in 25% and carcinoma in situ of cornea in 11.1%. Male patients outnumbered female (65.7% vs 34.3%) with 71.42% of patients above 60 years of age. The risk factors identified were: old age, ultraviolet B exposure and xeroderma pigmentosa. Treatment consisted of local resection with or without adjuvant therapy in 61.1%, exenteration in 30.5%, enucleation in 5.5% and chemo/radiotherapy in 2.7%. Intraocular invasion was seen in 5.5% and orbital spread in 30.5%. The frequency of OSSN was 0.37% among admitted patients. Identification of exact etiological factors will enable to formulate strategies that are likely to decrease the incidence of this disease and the associated morbidity and mortality. (author)

  11. p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Stephen

    2009-01-01

    from archival formalin fixed, paraffin-embedded donor tissues from 796 patients, and included cases of cervical intraepithelial neoplasia (CIN)1 (n = 249), CIN2 (n = 233), CIN3 (n = 181), and invasive cervical carcinoma (n = 133). p16INK4a expression was scored using two different protocols: 1......BACKGROUND: To evaluate the usefulness of this biomarker in the diagnosis of cases of cervical neoplasia we studied the immunohistochemical expression of p16INK4a in a large series of archival cervical biopsies arranged into tissue microarray format. METHODS: TMAs were constructed with tissue cores...... dysplasia or the presence of invasive carcinoma. CONCLUSION: Immunohistochemical analysis of p16INK4a expression is a useful diagnostic tool. Expression is related to the degree of histological dysplasia, suggesting that it may have prognostic and predicative value in the management of cervical neoplasia....

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

    Science.gov (United States)

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

    2013-04-01

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

  13. Anal squamous intraepithelial lesions in HIV+ MSM

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, M.L.

    2018-01-01

    In this thesis we report on several aspects of high-grade anal squamous intraepithelial lesions (HSIL) in HIV+ men who have sex with men (MSM). It is estimated that 10% of HIV+ MSM with anal HSIL will develop anal squamous cell carcinoma (ASCC) over 30 years time. Screening programs similar to

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

    Science.gov (United States)

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

    2013-02-01

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

  15. Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters

    NARCIS (Netherlands)

    H. Verloop (Herman); F.E. van Leeuwen (F.); T.J.M. Helmerhorst (Theo); I.M.C.M. de Kok (Inge); van Erp, E.J.M.; H.H. van Boven (Hester); M.A. Rookus (Matti)

    2017-01-01

    textabstractObjective: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear. Methods: We studied the risk of pre-cancerous (CIN) lesions and non-CCA

  16. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women

    DEFF Research Database (Denmark)

    Joura, Elmar A; Giuliano, Anna R; Iversen, Ole-Erik

    2015-01-01

    obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9v......HPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52...

  17. Association of Chlamydia trachomatis infection with human papillomavirus (HPV & cervical intraepithelial neoplasia - A pilot study

    Directory of Open Access Journals (Sweden)

    Neerja Bhatla

    2013-01-01

    Methods: A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2® (HC2 testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions. Results: HPV DNA was positive in 108 (18.0% women, CT DNA in 29 (4.8% women. HPV/CT co-infection was observed in only four (0.7% women. Of the 127 (21.2% women with Pap >ASCUS, 60 (47.2% were HPV positive and four (3.1% were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8% were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1% were HPV positive, two (4.3% were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P35 yr, higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05. Interpretation & conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions.

  18. Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women

    Science.gov (United States)

    Reimers, Laura L.; Sotardi, Susan; Daniel, David; Chiu, Lydia G.; Arsdale, Anne Van; Wieland, Daryl L.; Leider, Jason M.; Xue, Xiaonan; Strickler, Howard D.; Garry, David J.; Goldberg, Gary L.; Einstein, Mark H.

    2011-01-01

    Objective To determine predictors of treatment failure and recurrence after surgical excisional procedures for CIN in HIV-infected women. Methods A retrospective cohort study was conducted in which 136 eligible HIV-infected women treated for CIN between 1999 and 2005 were included. Data were abstracted from charts and computer databases. Treatment failures were defined as the presence of CIN 1+ at initial follow-up. Recurrences were defined as the presence of CIN 1+ subsequent to initial normal follow-up. Results Treatment failure at initial follow-up was common, occurring in 51% of CIN 1 and 55% of CIN 2+. Most lesions detected at treatment failure were high grade (>70%), regardless of the grade of initial lesion. Significant risk factors for treatment failure were loop electrosurgical excision procedure (LEEP) compared to cold knife conization (RR=1.76; 95% CI: 1.15–2.64), and low CD4+ count (p = 0.04). Among those with an initial normal clinical evaluation, 55% eventually recurred. As with treatment failure, most lesions detected at recurrence were high grade. Risk factors for recurrence included use of LEEP (hazard ratio [HR] = 3.38; 95% CI: 1.55–7.39), higher HIV RNA level, and the presence of positive margins at treatment (HR = 6.12; 95% CI: 1.90–19.73). Conclusions Most CIN treatment of HIV-infected women studied either failed or resulted in recurrence. Of particular concern, many of these subsequent lesions were high grade. Conization, however, was associated with significantly less failure/recurrence than LEEP. Clinicians treating CIN in HIV-infected women should avoid raising expectations of cure and instead focus on the achievable goal of cancer prevention until there are better therapies for this patient population. PMID:20605046

  19. One-session management of cervical intraepithelial neoplasia: a solution for developing countries.

    Science.gov (United States)

    Santos, C; Galdos, R; Alvarez, M; Velarde, C; Barriga, O; Dyer, R; Estrada, H; Almonte, M

    1996-04-01

    Six hundred thirty-nine patients with CIN on referral Pap were evaluated cytocolposcopically at the first visit and decided whether to be treated the same day or not. One hundred ninety-two patients (30%) were considered negative. Follow-up evidenced later appearance of CIN in five of them. One hundred fifty-three (24%) were candidates for delayed treatment due to conditions contraindicating same-day treatment. Two hundred ninety-four patients (46%) were randomly allocated in LEEP (149) or excisional laser (145) arms, and treated the same day under local anesthesia. Both arms were comparable. There were three microinvasive carcinomas diagnosed in the surgical specimen. LEEP was faster and produced less bleeding than laser, although required a mean of four slices to remove the lesion. Arterial hypertension after anesthetic infiltration was detected in 26% of cases. Two intraoperative and two delayed bleeders required surgery. The size of lesion and surgical defect were larger than those reported in the literature. Margins were involved in 8 patients (2.7%). Only 4.7% (7/149) of patients randomized to LEEP and 3.4% (5/145) with excisional laser had persistent or recurrent CIN on follow-up. Factors predisposing to failure included depth of surgical defect, grade of lesion, and operator's expertise. With this approach, 69% of patients referred for cytology of CIN were adequately managed in the first visit, which contrasts to classical management that reaches the state of treatment in 30% of patients. LEEP appears to be faster, less costly, and requires less expertise. Its use in conjunction with adequate screening is recommended for developing countries.

  20. [Reliability of endocervical curettage after conservative treatment of intraepithelial neoplasia of the cervix].

    Science.gov (United States)

    Lecointre, L; Akladios, C-Y; Averous, G; Lefebvre, F; Baulon, E; Thoma, V; Fender, M; Baldauf, J-J

    2015-02-01

    To evaluate the reliability of endocervical curettage (ECC) in patients previously treated for CIN. Retrospective analysis of data from 85 patients between January 1985 and December 2011 who received an ECC during monitoring after treatment of CIN. The reliability of the ECC was evaluated by comparison with the final histological analysis of the surgical specimen or the data for subsequent cyto-colpo-histological follow-up. Patients were referred to colposcopy either within the immediate post-treatment monitoring (n=42), meanly 9.7±5.3 months after treatment, or if cytological abnormalities were detected during long-term monitoring, meanly 78.6±52.4 months after treatment. Colposcopy was unsatisfactory in 75.3% of patients and normal colposcopic findings were found in 80% of patients. A perfect agreement between the ECC and the endocervical final diagnosis was noted in 68 patients (80%). For the diagnosis of severe cervical lesions (CIN 2+) ECC had a sensitivity of 86.2% (68.3-96.1), a specificity of 94.6% (85.1-98.9) and positive and negative predictive values of 61.4% (47.6-74.0) and 93% (83.0-98.1), respectively. The high sensitivity and negative predictive value of ECC for the diagnosis of severe post-therapeutic endocervical lesions avoid iterative treatment without increasing the risk of progression of a lesion to cancer. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Human papillomavirus and natural history of cervical intraepithelial neoplasia : clinical consequences

    NARCIS (Netherlands)

    M.A.E. Nobbenhuis (Marielle)

    2001-01-01

    textabstractCervical cancer is the second most common cancer in women world-wide after breast cancer. Each year, there are approximately 437,000 new cases of invasive cancer of the cervix diagnosed and more than 200,000 women die from the disease, 79% of which occur in developing countries. In the

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

    Directory of Open Access Journals (Sweden)

    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

  3. Intrathoracic neoplasia: Epidemiology and etiology

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1992-05-01

    Neoplasms of the thorax encompass those derived from the thoracic wall, trachea, mediastinum, lungs and pleura. They represent a wide variety of lesions including benign and malignant tumors arising from many tissues. The large surface area, 60 to 90 m{sup 2} in man, represented by the respiratory epithelium and associated thoracic structures are ideal targets for carcinogens carried by inspired air. The topic of discussion in this report is the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in animals and man. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms.

  4. Pulmonary preinvasive neoplasia.

    Science.gov (United States)

    Kerr, K M

    2001-04-01

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

  5. Multiple endocrine neoplasia type I

    International Nuclear Information System (INIS)

    Fischer, H.J.; Lois, J.F.; Gomes, A.S.

    1985-01-01

    A case of multiple endocrine neoplasia (Men) consisting of an unusual combination of an insulin-producing islet cell tumour and an adrenal adenoma is reported. CT clearly demonstrated the adrenal mass whereas the pancreatic lesion remained questionable. Conversely angiography located the pancreatic tumour but the adrenal findings were subtle. (orig.)

  6. Fibrobronchoscopy in the lung neoplasia

    International Nuclear Information System (INIS)

    Machin Gonzalez, Victoriano; Vieito Espinneira, Rodolfo; Freyre Serentill, Juan C.; Benito Soler, Isabel

    1997-01-01

    160 patients with a clinical-radiological picture suggesting lung neoplasia was conducted. Fibrobronchoscopy was performed as a reliable method to detect this disease. Punch biopsy, exfoliative cytology, and bronchial lavage Webre used to obtain specimens for the histological study. Of all the patients studied, 112 cases Webre positive and a proper diagnosis by biopsy was attained in 90 of them

  7. HER2/neu (c-erbB-2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimens

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Stephen

    2009-01-01

    intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity...... and invasive cervical carcinoma specimens. When present, Her-2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia....... This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia....

  8. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region

    OpenAIRE

    Castellsagué, Xavier; Ault, Kevin A.; Bosch, F. Xavier; Brown, Darron; Cuzick, Jack; Ferris, Daron G.; Joura, Elmar A.; Garland, Suzanne M.; Giuliano, Anna R; Hernandez-Avila, Mauricio; Huh, Warner; Iversen, Ole-Erik; Kjaer, Susanne K.; Luna, Joaquin; Monsonego, Joseph

    2016-01-01

    Background: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region Methods: Women ages 15–26 and 24–45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. Results: Pred...

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

    Science.gov (United States)

    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.

  10. Esophagectomy for Superficial Esophageal Neoplasia.

    Science.gov (United States)

    Watson, Thomas J

    2017-07-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  12. Intrahepatic splenosis mimicking hepatic neoplasia

    Directory of Open Access Journals (Sweden)

    Gabriel Neves Saad Teles

    Full Text Available Introduction: Splenosis is defined as the heterotopic autoimplantation of splenic tissue following trauma to or surgery on the spleen. Clinical case: We present a case of an asymptomatic 73-year-old male in whom hypervascular lesions were detected during routine exams. The patient reported a history of carotid artery surgery and cholecystectomy; he had a laparotomy incision from childhood but was unaware of the reason for it. The patient exhibited slightly elevated carcinoembryonic antigen (CEA levels. Histopathology revealed intrahepatic heterotopic splenic parenchyma, with no evidence of neoplasia in either of the two lesions, the diameters of which were 1.5 cm and 3.6 cm. Patient received outpatient follow-up care for 24 months and experienced no complications. Discussion: Our clinical, laboratory, and imaging exams failed to reveal the etiology of the lesion. Because the masses were hypervascular lesions, a percutaneous liver biopsy was not feasible. Conclusion: Through this report, we emphasize the importance of considering intrahepatic splenosis as a remote possibility in patients with hepatic nodules who have a history of splenectomy. Keywords: Splenosis, Neoplasia, Liver, Splenectomy

  13. Morphological and immunohistochemical pattern of tubo-ovarian dysplasia and serous tubal intraepithelial carcinoma.

    Science.gov (United States)

    Chene, Gautier; Cayre, Anne; Raoelfils, Ines; Lagarde, Nicole; Dauplat, Jacques; Penault-Llorca, Frederique

    2014-12-01

    Histopathological examination of material from prophylactic salpingo-oophorectomies performed in patients at genetic risk of ovarian cancer can reveal abnormalities interpreted as possible pre-cancerous "ovarian dysplasia" and tubal precursors lesions. We sought to study the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries and fallopian tubes (pBSO) in comparison with a group of serous tubal intraepithelial carcinoma (STIC) and non-cancerous controls. Morphological features and immunohistochemical expression patterns of Ki-67 (for proliferation biomarker), p53 (key pathway of mullerian serous tumorogenesis), Bcl2 (anti-apoptotic), γH2AX (a double-strand breaks marker) and ALDH1 (a stem cell marker significantly associated with early-stage ovarian cancer) were blindly evaluated by two pathologists in 111 pBSO, 12 STICs and 116 non-cancerous salpingo-oophorectomies (control group) (nBSO). Morphological ovarian and tubal dysplasia scores were significantly higher in the pBSO than in controls (respectively, 8.8 vs 3.12, pSTICs compared with the controls whereas expression patterns of Ki67, p53 and bcl2 were low to moderate in the pBSO group. STICs overexpressed Ki67 and p53 while bcl2 expression was low; Interestingly, ALDH1 expression was low in non dysplastic epithelium, high in dysplasia and constantly low in STICs. The morphological and immunohistochemical profile of tubo-ovarian dysplasia and STICs might be consistent with progression toward neoplastic transformation in the Serous Carcinogenesis Sequence. These changes may be pre-malignant and could represent an important phase in early neoplasia. ALDH1 activation in pBSO samples and its extinction in STICs should be considered as a target for prevention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

    Science.gov (United States)

    De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

    2008-11-01

    The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

  15. Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation

    Directory of Open Access Journals (Sweden)

    Thiery Jean

    2005-05-01

    Full Text Available Abstract Background We have previously reported activating mutations of the gene coding for the fibroblast growth factor receptor 3 (FGFR3 in invasive cervical carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we extended our study to screen a total of 75 invasive tumors and 80 cervical intraepithelial neoplasias (40 low-grade and 40 high-grade lesions. Results Using single strand conformation polymorphism (SSCP followed by DNA sequencing, we found FGFR3 mutation (S249C in all cases in 5% of invasive cervical carcinomas and no mutation in intraepithelial lesions. These results suggest that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02, and were more likely to be associated with a non-16/18 HPV type in their tumor. Gene expression analysis demonstrated that FGFR3 mutated tumors were associated with higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors. Supervised analysis of Affymetrix expression data identified a significant number of genes specifically differentially expressed in tumors with respect to FGFR3 mutation status. Conclusion This study suggest that tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening.

  16. Next Generation Sequencing of Tubal Intraepithelial Carcinomas

    Science.gov (United States)

    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

  17. Inflammatory Bowel Disease and Cervical Neoplasia

    DEFF Research Database (Denmark)

    Rungoe, Christine; Simonsen, Jacob; Riis, Lene

    2015-01-01

    BACKGROUND & AIMS: We examined the risk of cervical neoplasia (dysplasia or cancer) in women with ulcerative colitis (UC) or Crohn's disease (CD). We also calculated the reverse, the risk for diagnosis with cervical neoplasia before development of inflammatory bowel disease (IBD). METHODS: We...... established a national cohort of women diagnosed with UC (n = 18,691) or CD (n = 8717) between 1979 and 2011 and a control cohort of individually matched women from the general population (controls, n = 1,508,334). Incidence rate ratios (IRRs) of screening activity and diagnosis of cervical neoplasia in women...... with IBD were assessed by Cox proportional hazards regression analysis. Odds ratios (ORs) of cervical neoplasia before diagnosis of IBD were calculated by using conditional logistic regression. RESULTS: Women with CD underwent cervical cancer screening as often as women in the general population (IRR, 0...

  18. COMPUTED TOMOGRAPHIC EVALUATION OF CANINE PHARYNGEAL NEOPLASIA

    OpenAIRE

    Carozzi, Gregorio

    2016-01-01

    Computed tomography (CT) is commonly used to investigate head tumours in dogs, and is a fundamental part of the diagnostic work-up, for diagnosis, staging and planning therapy in neoplastic disease. Nasal diseases, either neoplastic or non-neoplastic diseases, oral neoplasia, brain disease, thyroid or carotid body neoplasia have been extensively studied. However little information are available for lesions of the pharyngeal area. In this thesis, cases of dogs affected by pharyngeal neoplas...

  19. Ocular Surface Squamous Neoplasia in Xeroderma Pigmentosum

    Directory of Open Access Journals (Sweden)

    Rajesh R Nayak

    2013-11-01

    Full Text Available Xeroderma pigmentosum (XP is a rare genetic disorder associated with multiple oculocutaneous and neurological manifestations. It occurs due to deficiency of the enzymes responsible for repairing ultraviolet radiation-induced DNA damage. Persistence of un-repaired DNA results in somatic mutations, leading to neoplasia of the skin and ocular surface. As this condition is rare, only isolated case reports of XP with ocular surface squamous neoplasia (OSSN are found in literature.

  20. Pretreatment Serum Cystatin C Levels Predict Renal Function, but Not Tumor Characteristics, in Patients with Prostate Neoplasia

    Directory of Open Access Journals (Sweden)

    Feilong Yang

    2017-01-01

    Full Text Available To evaluate the role of Cystatin C (Cys-C in tumorigenesis and progression of prostate cancer (PCa, we retrospectively collected the clinical information from the records of 492 benign prostatic hyperplasia (BPH, 48 prostatic intraepithelial neoplasia (PIN, and 173 PCa patients, whose disease was newly diagnosed and histologically confirmed. Pretreatment serum Cys-C levels were compared across the various groups and then analyzed to identify relationships, if any, with clinical and pathological characteristics of the PCa patient group. There were no significant differences in serum Cys-C levels among the three groups (P > 0.05. In PCa patients with normal SCr levels, patient age was correlated with serum Cys-C level (P ≤ 0.001 but did not correlate with alkaline phosphatase (AKP, lactate dehydrogenase (LDH, prostate specific antigen (PSA, Gleason score, or bone metastasis status (P > 0.05. Age and SCr contributed in part to the variations in serum Cys-C levels of PCa patients (r = 0.356, P ≤ 0.001; r = 0.520, P ≤ 0.001. In conclusion, serum Cys-C levels predict renal function in patients with prostate neoplasia, but were not a biomarker for the development of prostate neoplasia, and were not correlated with the clinicopathological characteristics of PCa.

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

    Science.gov (United States)

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

    2016-09-01

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

  2. Fluorescence detection of esophageal neoplasia

    Science.gov (United States)

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

    2008-06-01

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

  3. The Natural History of Neoplasia

    Science.gov (United States)

    Pitot, Henry C.

    1977-01-01

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

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

    Science.gov (United States)

    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

  5. 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 ...

  6. Inverse association between methylation of human papillomavirus type 16 DNA and risk of cervical intraepithelial neoplasia grades 2 or 3.

    Directory of Open Access Journals (Sweden)

    Long Fu Xi

    Full Text Available The clinical relevance of human papillomavirus type 16 (HPV16 DNA methylation has not been well documented, although its role in modulation of viral transcription is recognized.Study subjects were 211 women attending Planned Parenthood clinics in Western Washington for routine Papanicolaou screening who were HPV16 positive at the screening and/or subsequent colposcopy visit. Methylation of 11 CpG dinucleotides in the 3' end of the long control region of the HPV16 genome was examined by sequencing the cloned polymerase chain reaction products. The association between risk of CIN2/3 and degree of CpG methylation was estimated using a logistic regression model.CIN2/3 was histologically confirmed in 94 (44.5% of 211 HPV16 positive women. The likelihood of being diagnosed as CIN2/3 increased significantly with decreasing numbers of methylated CpGs (meCpGs in the 3' end of the long control region (P(for trend = 0.003. After adjusting for HPV16 variants, number of HPV16-positive visits, current smoking status and lifetime number of male sex partners, the odds ratio for the association of CIN2/3 with ≥4 meCpGs was 0.31 (95% confidence interval, 0.12-0.79. The proportion of ≥4 meCpGs decreased appreciably as the severity of the cervical lesion increased (P(for trend = 0.001. The inverse association remained similar when CIN3 was used as the clinical endpoint. Although not statistically significant, the ≥4 meCpGs-related risk reduction was more substantial among current, as compared to noncurrent, smokers.Results suggest that degree of the viral genome methylation is related to the outcome of an HPV16 cervical infection.

  7. A Phase I Trial of a Human Papillomavirus (HPV) DNA Vaccine for HPV16+ Cervical Intraepithelial Neoplasia 2/3

    Science.gov (United States)

    Trimble, Cornelia L.; Peng, Shiwen; Kos, Ferdynand; Gravitt, Patti; Viscidi, Raphael; Sugar, Elizabeth; Pardoll, Drew; Wu, TC

    2010-01-01

    Purpose: To evaluate the safety and immunogenicity of a therapeutic HPV16 DNA vaccine administered to women with HPV16+CIN2/3. Experimental Design: This phase I trial incorporated the standard ‘3+3” dose escalation design with an additional 6 patients allocated to the maximally tolerated dose (MTD). Healthy adult women with colposcopically-directed biopsy-proven HPV16+ CIN2/3 received three intramuscular (IM) vaccinations (0.5 mg, 1 mg, or 3mg) of a plasmid expressing a Sig-E7(detox)-HSP70 fusion protein on days 0, 28 and 56, and underwent standard therapeutic resection of the cervical squamocolumnar junction at day 105 (week 15). Safety and immunogenicity of the vaccine and histologic outcome based on resection at week 15 were assessed. Results: Fifteen patients were evaluable (3 each at 0.5 mg and 1mg, 9 at 3mg). The vaccine was well tolerated: most adverse events were mild transient injection-site discomfort; no dose-limiting toxicities were observed. Although HPVE7-specific T-cell responses to E7 detected by enzyme-linked immunospot assays (IFNγ) were of low frequency and magnitude, detectable increases in response subsequent to vaccination were identified in subjects in the second and third cohorts. Complete histologic regression occurred in 3/9 (33%, CI: 7%-70%)) individuals in the highest dose cohort, Although the difference is not significant, it is slightly higher than would be expected in an unvaccinated cohort (25%). Conclusions: This HPV16 DNA vaccine was safe and well tolerated. While it appears possible to elicit HPV-specific T cell responses in patients with established dysplastic lesions, other factors are likely to play a role in lesion regression. PMID:19118066

  8. Ultrastructural localization of human papilloma virus by nonradioactive in situ hybridization on tissue of human cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Multhaupt, H A; Rafferty, P A; Warhol, M J

    1992-01-01

    BACKGROUND: A nonradioactive in situ hybridization was developed to localize human papilloma virus (HPV) at the ultrastructural level. EXPERIMENTAL DESIGN: Cervical biopsies from human uterine cervices clinically suspicious of condyloma were embedded in Lowicryl K4M at low temperature...

  9. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, MPM; VanLeeuwen, AM; Hollema, H; Quint, WGV; Pieters, WJLM

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  10. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, M. P.; van Leeuwen, A. M.; Hollema, H.; Quint, W. G.; Pieters, W. J.

    1997-01-01

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  11. Neurocutaneous spectrum of multiple endocrine neoplasia-1

    Directory of Open Access Journals (Sweden)

    Shireen Furtado

    2012-01-01

    Full Text Available Multiple endocrine neoplasia type I or Wermer syndrome is characterized by primary hyperparathyroidism, enteropancreatic endocrine tumor, and a pituitary pathology. A 35-year-old male presented with visual field defects, hyperprolactinemia, and hypogonadism. He also had multiple infraumbilical skin-colored nodules. A syndromal association of Wermer syndrome was derived using the dermal, pituitary, parathyroid, and gastrointestinal hormonal manifestations of the tumor. The radiological and histological findings of lesion which underwent biopsy are discussed. The presence of collagenomas, lipomas, and hypopigmented macules in a patient with neuroendocrine symptoms should raise the suspicion of an underlying multiple endocrine neoplasia.

  12. Risk of metachronous neoplasia on surveillance colonoscopy in young patients with colorectal neoplasia.

    Science.gov (United States)

    Kim, Hyun Gun; Cho, Young-Seok; Cha, Jae Myung; Shin, Jeong Eun; Kim, Kyeong Ok; Yang, Hyo-Joon; Koo, Hoon Sup; Joo, Young-Eun; Boo, Sun-Jin

    2018-03-01

    Few prior reports exist that address the appropriate colonoscopy surveillance interval for individuals  .1). In the baseline low-risk adenoma group (n = 1869), the 5-year risk of metachronous advanced neoplasia was 4.9% in the younger patients on screening colonoscopy and 5.1% in the older patients (P > .1). Similarly, in the baseline no neoplasia group (n = 7013), the 5-year risk of metachronous advanced neoplasia was 4.1% in the younger patients on screening colonoscopy and 5.6% in the older patients (P > .1). Considering the similar risk of metachronous advanced neoplasia in younger and older individuals, we suggest a 3-year surveillance interval for high-risk adenoma and a 5-year surveillance interval for low-risk adenoma in young individuals without a strong family history. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2011-12-01

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

  14. Cervical intraepithelial lesions in females attending Women′s Health Clinics in Alexandria, Egypt

    Directory of Open Access Journals (Sweden)

    Mona Abdel-Hadi

    2015-01-01

    Full Text Available Background: Data from Egyptian studies provide widely varying estimates on the prevalence of preinvasive cervical lesions. The aim of this study was to estimate the rate of cervical intraepithelial neoplasia (CIN   in Egyptian women living in Alexandria to clarify the need for implementing a national organized screening program and a vaccination program in our community. Materials and Methods: The study was conducted over a 6 years period and covered the different socioeconomic levels to have a representative sample for women living in Alexandria. All women included did not have any cervical disorder related complaints. Conventional Pap smears were obtained and diagnosed using the Bethesda system. Women with abnormal Pap smears were managed according to the 2006 consensus guidelines within the available facilities. Persistent abnormal cytological results were referred for colposcopic biopsy. Histological results were grouped into: Reactive changes, CIN 1, CIN 2/CIN 3 and adenocarcinoma in-situ (AIS. Results: Out of the 6173 smears included in the study 6072 (98.36% were normal and only 101 (1.63% were abnormal. After colposcopic biopsies, 0.08% had CIN 1, 0.03% had CIN 2, 3 and 0.01% had AIS. Conclusion: We concluded that cervical cancer screening programs, although life-saving for a number of women, are not a sufficiently high priority in our community. Money for national health screening programs should preferably be directed more towards recruiting women for breast cancer screening, since breast cancer accounts for about 33% of all female cancers in Egypt ranking number one, while cervical cancer ranks number 13.

  15. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

    Science.gov (United States)

    Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2016-12-01

    The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  16. Microparticles and Exosomes in Gynecologic Neoplasias

    NARCIS (Netherlands)

    Nieuwland, Rienk; van der Post, Joris A. M.; Lok Gemma, Christianne A. R.; Kenter, G.; Sturk, Augueste

    2010-01-01

    This review presents an overview of the functions of microparticles and exosomes in gynecologic neoplasias. Growing evidence suggests that vesicles released from cancer cells in gynecologic malignancies contribute to the hypercoagulable state of these patients and contribute to tumor progression by

  17. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  18. Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy

    Directory of Open Access Journals (Sweden)

    Francesco Tonelli

    2012-01-01

    Full Text Available Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1 correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2 avoid persistent hypoparathyroidism; and 3 facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1 subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2 total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1 the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2 the surgeon's experience; 3 the timing of surgery; 4 the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay of the curative potential of the surgical procedure; and, 5 the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

  19. Mitotic and apoptotic activity in colorectal neoplasia.

    Science.gov (United States)

    Kohoutova, Darina; Pejchal, Jaroslav; Bures, Jan

    2018-05-18

    Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

  20. Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia

    Directory of Open Access Journals (Sweden)

    Frederico R. Romero

    2004-08-01

    Full Text Available OBJECTIVE: To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. MATERIALS AND METHODS: We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years. The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. RESULTS: We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma. We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. CONCLUSION: The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%. We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality

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

    Science.gov (United States)

    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

  2. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    International Nuclear Information System (INIS)

    Souchon, R.; Sautter-Bihl, M.L.; Sedlmayer, F.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Wenz, F.; Haase, W.

    2014-01-01

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly

  3. Canine oral cavity neoplasias - Brief review

    Directory of Open Access Journals (Sweden)

    João Filipe Requicha

    2015-03-01

    Full Text Available ABSTRACT. Requicha J.F., Pires M. dos A., Albuquerque C.M. & Viegas C.A. [Canine oral cavity neoplasias - Brief review.] Neoplasias da cavidade oral do cão - Breve revisão. Revista Brasileira de Medicina Veterinária, 37(1:41-46, 2015. Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande, 1749-024 Lisboa, Portugal e Department of Veterinary Sciences, School of Agriculture and Veterinary Sciences, University of Trás-os-Montes e Alto Douro, P.O. Box 1013, 5001-801 Vila Real, Portugal. E-mail: jfrequicha@gmail.com Oral proliferative lesions are relatively common in domestic carnivores but, fortunately, a lot of these lesions are benign. The oral cavity is place of 6% of all tumours in dogs, being the sixth most important localization of neoplasias in this specie. The non-odontogenic tumors arise from structures of the oral cavity, except from dental tissue, and they are mostly malignant. Odontogenic tumors are those originated from the dental structures. In the case of tumors of non-odontogenic, will be described the oral papillomatosis, the melanoma, the squamous cell carcinoma, and the fibrosarcoma. Among the odontogenic tumors, the focus will be on the epulides, ameloblastoma, odontoma and dentigerous cysts.

  4. HPV-genotypes in high-grade intraepithelial cervical lesions in Danish women

    DEFF Research Database (Denmark)

    Kirschner, Benny; Schledermann, Doris; Holl, Katsiaryna

    2013-01-01

    A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women.......A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women....

  5. 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

  6. 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.

  7. Endoscopic submucosal dissection for early Barrett's neoplasia.

    Science.gov (United States)

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

    2016-04-01

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

  8. What is your diagnosis? [Intestinal neoplasia

    International Nuclear Information System (INIS)

    Uehlinger, P.; Glaus, T.; Stoeckli, R.; Flueckiger, M.; Leuch, F.

    1997-01-01

    Iron lack anemia due to chronic blood loss was diagnosed in a 12-year-old dog. Clinical abnormalities included weakness and episodic vomiting. Typical hematological abnormalities were moderate regenerative anemia (Hct 21 %) and microcytosis (MCV 39 fl.). Chronic occult blood loss in adult dogs most commonly occurs in the gastrointestinal tract, associated with ulcus or neoplasia. Possible diagnostic steps include radiographs, abdominal ultrasound, gastroduodenoscopy, and exploratory laparotomy. In the present case gastric and duodenal adenocarcinomata were found during necropsy, confirming the clinical suspicion of a bleeding gastrointestinal malignancy

  9. Mamary neoplasia in a closed beagle colony

    International Nuclear Information System (INIS)

    Taylor, G.N.; Shabestari, L.; Williams, J.; Mays, C.W.; Angus, W.; McFarland, S.

    1975-01-01

    The incidence rate of mammary neoplasia in a large colony of beagles and its relationship to internal skeletal and/or liver radiation, age, relatively late ovariectomy (4 years and older), endometritis, parity status, and adrenal weight was examined. Of these various factors, age was the only condition that was clearly correlated with changes in the mammary tumor incidence. The rate became significant at approximately eight years of age and increased progressively throughout the successively older age classes. Within the female dogs, the incidence of mammary cancer was higher that that of any other form of spontaneous malignancy

  10. Molecular signatures of thyroid follicular neoplasia

    DEFF Research Database (Denmark)

    Borup, R.; Rossing, M.; Henao, Ricardo

    2010-01-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid...... a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules...... and robust genetic signature for the diagnosis of FA and FC. Endocrine-Related Cancer (2010) 17 691-708...

  11. New Developments in Ocular Surface Squamous Neoplasia

    Directory of Open Access Journals (Sweden)

    Ayşe Yağcı

    2014-09-01

    Full Text Available Ocular surface squamous neoplasia originates from conjunctiva epithelium and covers a broad spectrum of disease ranging from dysplasia to squamous cell carcinoma. Clinical features may vary from case to case. Traditional treatment of excision with no-touch technique combined with adjuvant therapies because of high recurrence rate. Main adjuvant treatments are cryotherapy and chemotherapy. In this review, clinical forms, differential diagnosis, American Joint Committee on Cancer classification and recent approaches to the management of ocular surface squamous dysplasia were described. (Turk J Ophthalmol 2014; 44: Supplement 8-14

  12. Primary pulmonary neoplasia in the dog and cat

    International Nuclear Information System (INIS)

    Mehlhaff, C.J.; Mooney, S.

    1985-01-01

    This article covers the pertinent clinical, physical, and radiographic findings in dogs and cats with primary pulmonary neoplasia. Diagnostic and treatment recommendations are made. Although primary pulmonary neoplasia is rare in both the dog and cat, it appears to be diagnosed with increasing frequency. Early detection and surgical treatment of carefully selected cases can prolong a good quality of life

  13. Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia

    NARCIS (Netherlands)

    Tobi, M; Cats, A; Maliakkal, BJ; Kinzie, JL; Maliakkal, R; Dullaart, RPF; Luk, GD

    Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published

  14. Molecular diagnosis of multiple endocrine neoplasia type 2A ...

    African Journals Online (AJOL)

    Molecular diagnosis of multiple endocrine neoplasia type 2A. RJ Pegoraro, DJ Hacking, RH Buck, L Rom, PA Lanning, GMB Berger. Abstract. Objective. To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. Subjects.

  15. NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.

    Science.gov (United States)

    Page-Karjian, Annie; Hahne, Megan; Leach, Kate; Murphy, Hayley; Lock, Brad; Rivera, Samuel

    2017-06-01

    A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.

  16. Immunologic assessment of patients with pulmonary metaplasia and neoplasia

    International Nuclear Information System (INIS)

    Gross, R.L.; Saccomanno, G.; Smith, D.M.; Saunders, R.; Thomas, R.G.

    1979-01-01

    Immune profiles have been obtained on 206 individuals including 57 controls, 50 lung cancer patients, and 99 uranium miners with well-defined sputum cytologies ranging from normal to carcinoma in situ. Little effect of smoking, uranium mining or a combination of mining plus smoking on immune function was observed if sputum cytology was normal. In heavy smokers there was a suggestion that total T cells are increased while T cell function is slightly depressed. Immunologic abnormalities were noted in the moderate atypia group where 40% had one or more abnormal immunologic parameters. Immunologic abnormalities were detected in 68 to 70 patients with marked atypia, carcinoma in situ, or invasive carcinoma. Further sequential study of the uranium miner population is necessary to define more precisely the predictive value of immunologic testing, and the role of early identification of high risk individuals in the early institution of definitive therapy, such as surgery or immunotherapy. Long-term prospective analysis of this population may also provide the answer to the question of whether alterations in immune function precede, or result from the appearance of cells committed to the development of neoplasia

  17. 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

    Directory of Open Access Journals (Sweden)

    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

  18. 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.

  19. Dermatologic symptoms associated with gastrointestinal neoplasia

    Directory of Open Access Journals (Sweden)

    Beata Młynarczyk-Bonikowska

    2017-03-01

    Full Text Available Gastrointestinal tumors are among the most common neoplastic causes of death worldwide. Presence of characteristic skin lesions can allow faster diagnosis and therapy and this way can increase the probability of a cure. In the paper we present the most important paraneoplastic syndromes that can coexist with gastrointestinal malignancy including colon, gastric, esophagus and pancreatic cancers. We take into account genetic syndromes such as Cowden syndrome, familial atypical multiple mole melanoma syndrome (FAMMM (melanoma/pancreatic cancer, Clarke Howel-Evans, Peutz-Jeghers, Muir-Torre, Gardner syndromes and acquired syndromes such as acantosis nigricans maligna, tripe palms, Leser-Trelat, Bazex, hypertrichosis languinosa, erythema gyratum repens , carcinoid and glucagonoma syndrome. We also include cutaneous metastases and coexistence of neoplasia in some cases of dermatomyositis.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. HPV 11, 16 and 18 DNA sequences in cervical swabs from women with cervical dysplasia: prevalence and associated risk of progression

    DEFF Research Database (Denmark)

    Hørding, U.; Daugaard, S.; Bock, J.E.

    1991-01-01

    Med.mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation......Med.mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation...

  3. Prevalence of human papillomavirus types 11, 16 and 18 in cervical swabs. A study of 1362 pregnant women

    DEFF Research Database (Denmark)

    Hørding, U.; Iversen, A.K.N.; Sebbelov, A.

    1990-01-01

    Med. mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation......Med. mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation...

  4. 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 (...

  5. Can the Ni classification of vessels predict neoplasia?

    DEFF Research Database (Denmark)

    Mehlum, Camilla Slot; Rosenberg, Tine; Dyrvig, Anne-Kirstine

    2018-01-01

    OBJECTIVES: The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non-neoplasia. We aimed to evaluate the ability...... of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia. DATA SOURCES: PubMed, Embase, Cochrane, and Scopus....... The pooled sensitivity and specificity of the Ni classification with two different cutoffs were calculated, and bubble and summary receiver operating characteristics plots were created. RESULTS: The combined sensitivity of five studies (n = 687) with Ni type IV-V defined as test-positive was 0.89 (95...

  6. Inmunología tumoral y neoplasias del sistema inmune

    OpenAIRE

    Sen Fernández, María Luz de la; Sempere Ortells, José Miguel; Marco, Francisco M.; Vázquez Araujo, Begoña

    2012-01-01

    Inmunología tumoral: vigilancia inmunológica, antígenos tumorales, respuesta inmune antitumoral, escape tumoral. Inmunología y diagnóstico. Inmunoterapia. Neoplasias del sistema inmune: leucemias y linfomas.

  7. Prostitution, HIV, and cervical neoplasia: a survey in Spain and Colombia.

    Science.gov (United States)

    de Sanjosé, S; Palacio, V; Tafur, L; Vazquez, S; Espitia, V; Vazquez, F; Roman, G; Muñoz, N; Bosch, F X

    1993-01-01

    The prevalence of cervical intraepithelial neoplasia (CIN) and the association of CIN with prostitution was examined in Oviedo, a region in Spain with low incidence of cervical cancer, and in Cali, Colombia, where the incidence of cervical cancer is 6-10 times higher. In Oviedo, the study included 758 prostitutes attending a sexually transmitted diseases clinic and 1203 nonprostitutes attending a family-planning clinic. In Cali, 775 prostitutes and 1795 nonprostitutes attending health centers were included. Seropositivity to common sexually transmitted agents was investigated in Spanish prostitutes. No significant difference was found in the prevalence of CIN between Oviedo and Cali in both prostitutes (2.5 versus 1.8%) and nonprostitutes (1.2 versus 1.1%). Prostitutes had a 2-fold increased risk of CIN as compared to nonprostitutes; in Spain, the prevalence odds ratio (POR) was 2.3 and the 95% confidence interval (CI) was 1.1-4.5, and, in Colombia, POR was 1.8 and the 95% CI was 0.9-3.5. Among prostitutes in Oviedo, human immunodeficiency virus (HIV) prevalence was 4.9% and HIV-positive prostitutes showed a high risk of CIN as compared to HIV-negative prostitutes (POR, 12.7; 95% CI, 3.9-40.9); 76% of HIV-positive prostitutes were i.v. drug users and showed an increased seroprevalence of other sexually transmitted diseases. HIV-negative prostitutes did not show any increased risk of CIN (POR, 1.2; 95% CI, 0.5-2.8). These results show that among nonprostitutes the prevalence of CIN was not statistically different between the two cities in Spain and Colombia; prostitutes were at moderate increased risk compared to nonprostitutes in both cities.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Lobular neoplasia: frequency and association with other breast lesions

    Directory of Open Access Journals (Sweden)

    Gobbi Helenice

    2011-08-01

    Full Text Available Abstract Background Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions. Methods Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008. Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend. Results We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4% that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%. Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2% as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular

  12. Anal intraepitelial neoplasia: a narrative review

    Directory of Open Access Journals (Sweden)

    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.

  13. Radiogenic neoplasia in thyroid and mammary clonogens

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1993-01-01

    The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Intraepithelial lymphocytes express junctional molecules in murine small intestine

    International Nuclear Information System (INIS)

    Inagaki-Ohara, Kyoko; Sawaguchi, Akira; Suganuma, Tatsuo; Matsuzaki, Goro; Nawa, Yukifumi

    2005-01-01

    Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), β-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. γδ IEL showed higher level of these expressions than αβ IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC

  16. Serous endometrial intraepithelial carcinoma: a case series and literature review

    International Nuclear Information System (INIS)

    Pathiraja, P; Dhar, S; Haldar, K

    2013-01-01

    Minimal uterine serous cancer (MUSC) or serous endometrial intraepithelial carcinoma (EIC) has been described by many different names since 1998. There have been very few cases reported in literature since EIC/MUSC was recognized as a separate entity. The World health Organization (WHO) Classification favors the term serous EIC. Although serous EIC is confined to the uterine endometrium at initial histology diagnosis, a significant number of patients could have distal metastasis at diagnosis, without symptoms. Serous EIC is considered as being the precursor of uterine serous cancer (USC), but pure serous EIC also has an aggressive behavior similar to USC. It is therefore prudent to have an accurate diagnosis and appropriate surgical staging. There are very few published articles in literature that discuss the pure form of serous EIC. The aim of this series is to share our experience and review evidence for optimum management of serous EIC. We report a series of five women treated in our institute in the last 3 years. We reviewed the relevant literature on serous EIC and various management strategies, to recommend best clinical practice. Pure serous EIC is a difficult histopathological diagnosis, which requires ancillary immunohistochemical staining. It can have an aggressive clinical behavior with early recurrence and poor survival. Optimum surgical staging, with appropriate adjuvant treatment, should be discussed when treating these patients

  17. Next-Generation Sequencing of Tubal Intraepithelial Carcinomas.

    Science.gov (United States)

    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.

  18. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Souchon, R. [University Hospital Tuebingen, Klinik fuer Radioonkologie, Tuebingen (Germany); Sautter-Bihl, M.L. [Municipal Hospital Karlsruhe, Karlsruhe (Germany); Sedlmayer, F. [LKH Salzburg, Paracelsus Medical University Hospital, Salzburg (Austria); Budach, W. [University Hospital Duesseldorf, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, P. [Klinikum Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Harms, W. [St. Clara Hospital, Basel (Switzerland); Wenz, F. [University Hospital Mannheim, Mannheim (Germany); Haase, W.

    2014-01-15

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy

  19. [Heredity in renal and prostatic neoplasia].

    Science.gov (United States)

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

    1997-09-01

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

  20. DCLK1 immunoreactivity in colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Bellows CF

    2012-04-01

    Full Text Available Giuseppe Gagliardi1, Monica Goswami1, Roberto Passera2, Charles F Bellows11Department of Surgery and Pathology, Tulane University, New Orleans, LA, USA; 2Division of Nuclear Medicine Azienda Ospedaliero-Universitaria San Giovanni Battista, Turin, ItalyIntroduction: Microtubule-associated doublecortin and CaM kinase-like-1 (DCLK1 is a novel candidate marker for intestinal stem cells. The aim of our study was to assess DCLK1 immunoreactivity in colorectal carcinogenesis and its correlation with prognosis.Methods: DCLK1 immunostaining was performed in colorectal tissue from 71 patients, including 18 adenomatous polyps, 40 primary adenocarcinomas, and 14 metastatic lesions. Each case was evaluated by a combined scoring method based on the intensity of staining (score 0–3 and the percentage of tissue staining positive (score 0–3. Immunoexpression for DCLK1 was considered as positive when the combined score was 2–6 and negative with a score of 0–1.Results: Overall, 14/18 (78% of polyps, 30/40 (75% of primary adenocarcinomas, and 7/14 (50% of distant metastases were positive for DCLK1. In adenomatous polyps and primary cancer there was no association between DCLK1 staining score and tumor pathology. However, after curative colorectal cancer resection, patients whose tumor had a high (≥5 combined staining score had increased cancer-specific mortality compared to patients with low (0–4 staining score (hazard ratio 5.89; 95% confidence interval: 1.22–28.47; P = 0.027.Conclusion: We found that DCLK1 is frequently expressed in colorectal neoplasia and may be associated with poor prognosis. Further studies are necessary to validate the use of DCLK1 as a prognostic marker.Keywords: DCLK1, DCAMKL-1, gastrointestinal stem cell, cancer stem cell, adenomatous polyps, liver metastasis, immunohistochemistry

  1. Radiogenic neoplasia in thyroid and mammary clonogens

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1992-01-01

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process

  2. Cutaneous neoplasia following PUVA therapy for psoriasis

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, K.E.; Handley, J.; McGinn, S.; Allen, G. [Belfast City Hospital (United Kingdom). Dept. of Dermatology; Patterson, C.C. [Queen`s Univ., Belfast, Northern Ireland (United Kingdom)

    1996-04-01

    To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA), we reviewed patients with psoriasis treated at out unit between 1979 and 1991. Two hundred and forty-five patients were assessed, with a median duration of follow-up of 9.5 years. Fifty-nine per cent were male, and 41% female. The median number of exposures was 59, and the median total dose was 133J/cm{sup 2} for the group as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2.4%), basal cell carcinoma occurred in all six and one individual also developed four squamous cell carcinomas and Bowen`s disease of the penis. No cases of malignant melanoma were recorded. Patients who developed NMSC received a median number of 225 exposures and a median cumulative dose of 654J/cm{sup 2}. Compared with a control study population in West Glamorgan, Wales, there was a 1.4 (95% confidence limits (CL) 0.5 and 3.1) times increased risk of NMSC. A statistically significant increased incidence of NMSC was found for patients who had received 100 or more exposures, and 250 or more J/cm{sup 2}, with risks of 3.7 (95% CL 1.0 and 9.5), and 4.0 (95% CL 1.1 and 10), respectively. A PUVA dose of < 250 J/cm{sup 2} or < 100 exposures conferred a minimal increase in risk of NMSC in our study population. (author).

  3. Radiogenic neoplasia in thyroid and mammary clonogens

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1991-01-01

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process

  4. Neoplasias malignas: caracterización

    Directory of Open Access Journals (Sweden)

    Freddie Hernández Cisneros

    1997-02-01

    Full Text Available Se realizó un estudio transversal con el objetivo de caracterizar a los pacientes con neoplasias malignas en un área de salud desde marzo de 1994 hasta agosto del mismo año; el universo de estudio estuvo representado por 75 pacientes diagnosticados con algún tipo de afección maligna y el registro primario de los datos, por una encuesta con variables seleccionadas; se procesó la información de una forma computadorizada. Se encontraron como resultados más importantes: una mayor incidencia en el grupo de edad de 50 años y más; un 56 % fumaba y un 17,33 % ingería bebidas alcohólicas; las 3 localizaciones más frecuentes fueron: mama, cuello del útero y piel, y se detectaron deficiencias llamativas en la promoción y la prevención de estas enfermedades.: A cross-sectional study was carried out, with the aim of characterizing the patients with malignant neoplasms in a health area, from March 1994 to August of the same year; the universe of study was represented by 75 patients diagnosed with some kind of malignant disease, and the primary score of the data, by means of a survey with selected variables; information was processed in a computed way. The most important results found, were: the highest incidence in the 50 years old or more age group; the 56 % smoked, and the 17.33 % drank alcoholic beverages; the three most frequent sites, were: breast, cervix uteri and skin, and also outstanding defficiencies were detected in the promotion and prevention of these diseases.

  5. Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications.

    Science.gov (United States)

    Carlson, Joseph W; Jarboe, Elke A; Kindelberger, David; Nucci, Marisa R; Hirsch, Michelle S; Crum, Christopher P

    2010-07-01

    Serous tubal intraepithelial carcinoma (STIC) is detected in between 5% and 7% of women undergoing risk-reduction salpingooophorectomy for mutations in the BRCA1 or 2 genes (BRCA+), and seems to play a role in the pathogenesis of many ovarian and "primary peritoneal" serous carcinomas. The recognition of STIC is germane to the management of BRCA+ women; however, the diagnostic reproducibility of STIC is unknown. Twenty-one cases were selected and classified as STIC or benign, using both hematoxylin and eosin and immunohistochemical stains for p53 and MIB-1. Digital images of 30 hematoxylin and eosin-stained STICs (n=14) or benign tubal epithelium (n=16) were photographed and randomized for blind digital review in a Powerpoint format by 6 experienced gynecologic pathologists and 6 pathology trainees. A generalized kappa statistic for multiple raters was calculated for all groups. For all reviewers, the kappa was 0.333, indicating poor reproducibility; kappa was 0.453 for the experienced gynecologic pathologists (fair-to-good reproducibility), and kappa=0.253 for the pathology residents (poor reproducibility). In the experienced group, 3 of 14 STICs were diagnosed by all 6 reviewers, and 9 of 14 by a majority of the reviewers. These results show that interobserver concordance in the recognition of STIC in high-quality digital images is at best fair-to-good for even experienced gynecologic pathologists, and a proportion cannot be consistently identified even among experienced observers. In view of these findings, a diagnosis of STIC should be corroborated by a second pathologist, if feasible.

  6. p53 tumor suppressor gene: significance in neoplasia - a review

    International Nuclear Information System (INIS)

    Alam, J.M.

    2000-01-01

    p53 is a tumor suppressor gene located on chromosome 17p13.1. Its function includes cell cycle control and apoptosis. Loss of p53 function, either due to decreased level or genetic transformation, is associated with loss of cell cycle control, decrease, apoptosis and genomic modification, such mutation of p53 gene is now assessed and the indicator of neoplasia of cancer of several organs and cell types, p53 has demonstrated to have critical role in defining various progressive stages of neoplasia, therapeutic strategies and clinical application. The present review briefly describes function of p53 in addition to its diagnostic and prognostic significance in detecting several types of neoplasia. (author)

  7. 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.

  8. Use of mammary epithelial antigens as markers in mammary neoplasia

    International Nuclear Information System (INIS)

    Ceriani, R.L.; Peterson, J.A.; Blank, E.W.

    1979-01-01

    Cell-type specific antigens of the mammary epithelial cells can be used as markers of breast neoplasia. Methods are proposed for the detection of metastatic mammary tissue in vivo by injection of [ 125 I]-labeled antibodies against the mammary epithelial antigens. In addition, the reduced expression of mammary epithelial cell antigens in neoplastic breast cells, quantitated here on a cell per cell basis by flow cytofluorimetry, is a marker of neoplasia and an indication of a deletion accompanying the neoplastic transformation of these cells. (Auth.)

  9. The Danish National Chronic Myeloid Neoplasia Registry

    Directory of Open Access Journals (Sweden)

    Bak M

    2016-10-01

    Full Text Available Marie Bak,1 Else Helene Ibfelt,2 Thomas Stauffer Larsen,3 Dorthe Rønnov-Jessen,4 Niels Pallisgaard,5 Ann Madelung,6 Lene Udby,1 Hans Carl Hasselbalch,1 Ole Weis Bjerrum,7 Christen Lykkegaard Andersen1,7 1Department of Hematology, Zealand University Hospital, University of Copenhagen, Roskilde, 2Research Centre for Prevention and Health, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, 3Department of Hematology, Odense University Hospital, Odense, 4Department of Hematology, Vejle Hospital, Vejle, 5Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Roskilde, 6Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Næstved, 7Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim: The Danish National Chronic Myeloid Neoplasia Registry (DCMR is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. Study population: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia. Main variables: Data are collected using standardized registration forms (so far up to four forms per patient, which are consecutively filled out online at time of diagnosis, after 2-year and 5-year follow-ups, and at end of follow-up. The forms include variables that describe clinical/paraclinical assessments, treatment, disease progression, and survival – disease-specific variables – as well as variables that are identical for all chronic myeloid malignancies. Descriptive

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

    Science.gov (United States)

    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.

  11. Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings

    NARCIS (Netherlands)

    Yang, Nan; Eijsink, Jasper J. H.; Lendvai, Agnes; Volders, Haukeline H.; Klip, Harry; Buikema, Henk J.; van Hemel, Bettien M.; Schuuring, Ed; van der Zee, Ate G. J.; Wisman, G. Bea A.

    2009-01-01

    Purpose: Recently, we reported 13 possible cervical cancer-specific methylated biomarkers identified by pharmacologic unmasking microarray in combination with large-genome computational screening. The aim of the present study was to perform an in-depth analysis of the methylation patterns of these

  12. Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings

    NARCIS (Netherlands)

    Yang, Nan; Eijsink, Jasper J. H.; Lendvai, Agnes; Volders, Haukeline H.; Klip, Harry; Buikema, Henk J.; van Hemel, Bettien M.; Schuuring, Ed; van der Zee, Ate G. J.; Wisman, G. Bea A.

    Purpose: Recently, we reported 13 possible cervical cancer-specific methylated biomarkers identified by pharmacologic unmasking microarray in combination with large-genome computational screening. The aim of the present study was to perform an in-depth analysis of the methylation patterns of these

  13. Pathological discrepancy between colposcopic directed cervical biopsy and Loop Electrosurgical-Excision Procedures (LEEPs in patients with biopsies proven high grade cervical intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Sitchuphong Noothong

    2017-10-01

    Conclusion: The prevalence of patients with CIN1 or less from LEEP specimens who previously had colposcopic biopsies proven CIN2 or 3 was 16.3%. CIN2 from biopsy was the statistically significant risk factor of CIN1 or less in LEEP specimens.

  14. One-Session Management of Cervical Intraepithelial Neoplasia: A Solution for Developing Countries. A Prospective, Randomized Trial of LEEP versus Laser Excisional Conization

    Science.gov (United States)

    Santos; Galdos; Alvarez; Velarde; Barriga; Dyer; Estrada; Almonte

    1996-04-01

    Six hundred thirty-nine patients with CIN on referral Pap were evaluated cytocolposcopically at the first visit and decided whether to be treated the same day or not. One hundred ninety-two patients (30%) were considered negative. Follow-up evidenced later appearance of CIN in five of them. One hundred fifty-three (24%) were candidates for delayed treatment due to conditions contraindicating same-day treatment. Two hundred ninety-four patients (46%) were randomly allocated in LEEP (149) or excisional laser (145) arms, and treated the same day under local anesthesia. Both arms were comparable. There were three microinvasive carcinomas diagnosed in the surgical specimen. LEEP was faster and produced less bleeding than laser, although required a mean of four slices to remove the lesion. Arterial hypertension after anesthetic infiltration was detected in 26% of cases. Two intraoperative and two delayed bleeders required surgery. The size of lesion and surgical defect were larger than those reported in the literature. Margins were involved in 8 patients (2.7%). Only 4.7% (7/149) of patients randomized to LEEP and 3.4% (5/145) with excisional laser had persistent or recurrent CIN on follow-up. Factors predisposing to failure included depth of surgical defect, grade of lesion, and operator's expertise. With this approach, 69% of patients referred for cytology of CIN were adequately managed in the first visit, which contrasts to classical management that reaches the state of treatment in 30% of patients. LEEP appears to be faster, less costly, and requires less expertise. Its use in conjunction with adequate screening is recommended for developing countries.

  15. Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands

    NARCIS (Netherlands)

    Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Daemen, Toos CAHH; Postma, Maarten J.

    2016-01-01

    In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of

  16. Detection of human papillomavirus by hybrid capture and real time PCR methods in patients with chronic cervicitis and cervical intraepithelial

    Directory of Open Access Journals (Sweden)

    Elisha Khandker

    2016-07-01

    Full Text Available Background and objectives:Cervical cancer due to Human papillomavirus (HPV is one of the leading causes of morbidity and mortality in women. Testing of HPV can identify women who are at risk of cervical cancer. Nowadays, molecular methods like real time polymerase chain reaction (PCR and hybrid capture technique are applied for detecting HPV in cervical specimens. The objective of the present study was to determine the rate of HPV infection in women with chronic cervicitis and cervical intraepithelial neoplasia (CIN by a commercial real time polymerase chain reaction test kit and by a hybrid capture HPV DNA test. Methods:Women aged between 20 to 55 years with chronic cervicitis and CIN were enrolled in the study after obtaining informed consent. Cervical specimen was collected by using cervical brush and stored in transport medium until used. HPV was detected by High Risk Screen Real-TM Quant 2x (Sacace, Biotechnologies SrI, Italy real time PCR kit (HR RT-PCR and by Hybrid Capture-2 High-Risk HPV DNA (Hc-2; Digene Corporation, USA test. Results: Total 72 women with chronic cervicitis and CIN of different grades were included in the study. Out of this, HPV infection detected by HR RT-PCR was 31 (43% and by Hc-2 was 14 (19.4%. Both the tests were able to detect HPV infection in all the CIN 3 cases and in most of the CIN 2 cases. However, HR RT-PCR detected higher number of HPV in chronic cervicitis and CIN1 cases. Conclusion:The study has shown that HR RT-PCR and Hc-2 tests are equally effective in detecting HPV infection in patients with CIN 2 and CIN 3 lesions. However, HR RT-PCR is more sensitive test for detecting HPV in chronic cervicitis and early CIN lesions and, therefore can be used in epidemiological study to detect presence of HPV in general population. IMC J Med Sci 2016; 10(2: 45-48

  17. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-12-01

    Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.

  18. Imaging Finding of Multiple Endocrine Neoplasia Type 1: Case Report

    International Nuclear Information System (INIS)

    Yum, Tae Jun; Cho, Hee Woo

    2012-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome with characteristic clinical and radiological manifestations. Many reports on MEN1 have been published; however, no cases of radiologically diagnosed MEN1 have been reported. Therefore, we report on a radiologically diagnosed case of MEN1 with clinical symptoms of gastroduodenal ulcer.

  19. Nuclear Receptors and Multiple Endocrine Neoplasia type 1 (MEN1)

    NARCIS (Netherlands)

    Dreijerink, K.M.A.

    2009-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome that is characterized by the occurrence of tumours of the parathyroid glands, gastroenteropancreatic tumours, pitui-tary gland adenomas, as well as adrenal adenomas and neuro-endocrine tumours, often at a young age. MEN1 tumours can

  20. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region.

    Science.gov (United States)

    Castellsagué, Xavier; Ault, Kevin A; Bosch, F Xavier; Brown, Darron; Cuzick, Jack; Ferris, Daron G; Joura, Elmar A; Garland, Suzanne M; Giuliano, Anna R; Hernandez-Avila, Mauricio; Huh, Warner; Iversen, Ole-Erik; Kjaer, Susanne K; Luna, Joaquin; Monsonego, Joseph; Muñoz, Nubia; Myers, Evan; Paavonen, Jorma; Pitisuttihum, Punnee; Steben, Marc; Wheeler, Cosette M; Perez, Gonzalo; Saah, Alfred; Luxembourg, Alain; Sings, Heather L; Velicer, Christine

    2016-12-01

    We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region METHODS: Women ages 15-26 and 24-45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81-85%). Types 31/33/45/52/58 accounted for 25-30% of CIN1 in Latin America and Europe, but 14-18% in North America and Asia. Types 31/33/45/52/58 accounted for 33-38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17-18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2-11% of CIN2/3. The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

    Science.gov (United States)

    Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-01-01

    SUMMARY PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

  2. Testicular neoplasia in undescended testes of cryptorchid boys-does surgical strategy have an impact on the risk of invasive testicular neoplasia?

    DEFF Research Database (Denmark)

    Cortes, Dina; Thorup, Jørgen Mogens; Petersen, Bodil Laub

    2004-01-01

    We investigated whether or not surgical strategy has an impact on the risk of invasive testicular neoplasia in cases of cryptorchidism. We made a database study of the incidence of testicular neoplasia at surgery for cryptorchidism in childhood, and evaluated if such abnormalities were found......, p placed...

  3. 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.

    Science.gov (United States)

    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.

  4. Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

    International Nuclear Information System (INIS)

    Terry, Mary Beth; Neugut, Alfred I; Mansukhani, Mahesh; Waye, Jerome; Harpaz, Noam; Hibshoosh, Hanina

    2003-01-01

    The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG 2 a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508). p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7). Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence

  5. Multiple endocrine neoplasia type 2: achievements and current challenges

    Directory of Open Access Journals (Sweden)

    Andreas Machens

    2012-01-01

    Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

  6. Gestational trophoblastic neoplasia: A 6 year retrospective study

    Directory of Open Access Journals (Sweden)

    Sushruta Shrivastava

    2014-01-01

    Full Text Available Aims and Objectives: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. Materials and Methods: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score /=7 received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Results: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67% achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27 achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27. Conclusion: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

  7. Piroxicam decreases postirradiation colonic neoplasia in the rat.

    Science.gov (United States)

    Northway, M G; Scobey, M W; Cassidy, K T; Geisinger, K R

    1990-12-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation.

  8. Piroxicam decreases postirradiation colonic neoplasia in the rat

    International Nuclear Information System (INIS)

    Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R.

    1990-01-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references

  9. Piroxicam decreases postirradiation colonic neoplasia in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R. (Wake Forest Univ., Winston Salem, NC (USA))

    1990-12-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references.

  10. 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH).

    Science.gov (United States)

    Cortés-Gutiérrez, Elva I; Ortíz-Hernández, Brenda L; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Fernández, José Luis; López-Fernández, Carmen; Gosálvez, Jaime

    2013-02-19

    We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

  11. 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH

    Directory of Open Access Journals (Sweden)

    Jaime Gosálvez

    2013-02-01

    Full Text Available We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH. A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL, 10 with high-grade SIL (HG-SIL, and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

  12. A Simple Laparoscopic Procedure to Restore a Normal Vaginal Length After Colpohysterectomy With Large Upper Colpectomy for Cervical and/or Vaginal Neoplasia.

    Science.gov (United States)

    Leblanc, Eric; Bresson, Lucie; Merlot, Benjamin; Puga, Marco; Kridelka, Frederic; Tsunoda, Audrey; Narducci, Fabrice

    2016-01-01

    Colpohysterectomy is sometimes associated with a large upper colpectomy resulting in a shortened vagina, potentially impacting sexual function. We report on a preliminary experience of a laparoscopic colpoplasty to restore a normal vaginal length. Patients with shortened vaginas after a laparoscopic colpohysterectomy were considered for a laparoscopic modified Davydov's procedure to create a new vaginal vault using the peritoneum of the rectum and bladder. From 2010 to 2014, 8 patients were offered this procedure, after informed preoperative consent. Indications were 2 extensive recurrent vaginal intraepithelial neoplasias grade 3 and 6 radical hysterectomies for cervical cancer. Mean vaginal length before surgery was 3.8 cm (standard deviation, 1.6). Median operative time was 50 minutes (range, 45-90). Blood loss was minimal (50-100 mL). No perioperative complications occurred. Median vaginal length at discharge was 11.3 cm (range, 9-13). Sexual intercourse could be resumed around 10 weeks after surgery. At a median follow-up of 33.8 months (range, 2.4-51.3), 6 patients remained sexually active but 2 had stopped. Although this experience is small, this laparoscopic modified Davydov's procedure seems to be an effective procedure, adaptable to each patient's anatomy. If the initial postoperative regular self-dilatation is carefully observed, vaginal patency is durably restored and enables normal sexual function. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  13. Zinc finger arrays binding human papillomavirus types 16 and 18 genomic DNA: precursors of gene-therapeutics for in-situ reversal of associated cervical neoplasia

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2012-07-01

    Full Text Available Abstract Background Human papillomavirus (HPV types 16 and 18 are the high-risk, sexually transmitted infectious causes of most cervical intraepithelial neoplasias (CIN or cancers. While efficacious vaccines to reduce the sexual acquisition of these high-risk HPVs have recently been introduced, no virus-targeted therapies exist for those already exposed and infected. Considering the oncogenic role of the transforming (E6 and E7 genes of high-risk HPVs in the slow pathogenesis of cervical cancer, we hypothesize that timely disruption or abolition of HPV genome expression within pre-cancerous lesions identified at screening may reverse neoplasia. We aimed to derive model zinc finger nucleases (ZFNs for mutagenesis of the genomes of two high-risk HPV (types 16 & 18. Methods and results Using ZiFiT software and the complete genomes of HPV types16 and 18, we computationally generated the consensus amino acid sequences of the DNA-binding domains (F1, F2, & F3 of (i 296 & 327 contextually unpaired (or single three zinc-finger arrays (sZFAs and (ii 9 & 13 contextually paired (left and right three- zinc-finger arrays (pZFAs that bind genomic DNA of HPV-types 16 and 18 respectively, inclusive of the E7 gene (s/pZFAHpV/E7. In the absence of contextually paired three-zinc-finger arrays (pZFAs that bind DNA corresponding to the genomic context of the E6 gene of either HPV type, we derived the DNA binding domains of another set of 9 & 14 contextually unpaired E6 gene-binding ZFAs (sZFAE6 to aid the future quest for paired ZFAs to target E6 gene sequences in both HPV types studied (pZFAE6. This paper presents models for (i synthesis of hybrid ZFNs that cleave within the genomic DNA of either HPV type, by linking the gene sequences of the DNA-cleavage domain of the FokI endonuclease FN to the gene sequences of a member of the paired-HPV-binding ZFAs (pZFAHpV/E7 + FN, and (ii delivery of the same into precancerous lesions using HPV-derived viral plasmids or

  14. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  15. Early Diagnosis of Breast Cancer by Identifying Malignant Cells Within Neoplasias Histologically Classified as Benign

    National Research Council Canada - National Science Library

    Lelievre, Sophie A

    2005-01-01

    Current diagnostic tools permit the classification of breast neoplasias into categories that represent different relative risks of developing cancer, but they do not indicate which particular lesion...

  16. Squamous intraepithelial lesions of the anal squamocolumnar junction: Histopathological classification and HPV genotyping

    Directory of Open Access Journals (Sweden)

    Omar Clavero

    2017-06-01

    Full Text Available Background: Human papillomavirus (HPV-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ. We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and –positive patients. Methods: Histopathology identified 47 squamous intraepithelial lesions (SILs adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping. Results: Sixteen (16/47 of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47 were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM; Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6. Conclusions: Clinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative. Keywords: Anal squamocolumnar junction, Low-grade squamous intraepithelial lesion (LSIL, High-grade squamous intraepithelial lesion (HSIL, Papillary immature metaplasia (PIM, HPV, HIV

  17. 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.

    Science.gov (United States)

    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.

  18. Investigating work-related neoplasia associated with solar radiation.

    Science.gov (United States)

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

    2015-01-01

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

  19. Male pattern baldness and risk of colorectal neoplasia.

    Science.gov (United States)

    Keum, N; Cao, Y; Lee, D H; Park, S M; Rosner, B; Fuchs, C S; Wu, K; Giovannucci, E L

    2016-01-12

    Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33). Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia.

  20. Imaging of multiple endocrine neoplasia (MEN II A)

    International Nuclear Information System (INIS)

    Tanaka, Hiroko; Kohno, Atsushi; Nojiri, Yoko

    1995-01-01

    A retrospective review of diagnostic imaging findings of 20 cases of multiple endocrine neoplasia II A (MEN II A) was performed. The characteristic findings of thyroidal medullary carcinomas were relatively well-defined hypo- to isoechoic masses on US and coarse calcifications on plain X-ray. The pheochromocytomas were smaller in size and less enhancing than the sporadic ones, and they revealed marked high intensity on T2WI of MRI. We consider that these imaging findings were useful for the supplementary diagnosis of MEN II A. (author)

  1. Endoscopic submucosal dissection for early Barrett’s neoplasia

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

  3. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    DEFF Research Database (Denmark)

    Kaltoft, Nicolai; Tilotta, Maria C; Witte, Anne-Barbara

    2010-01-01

    colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 microM), various stimulators...

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

    Science.gov (United States)

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

    2016-10-01

    , interferon (IFN)-γ (Th1-driven), IL-4, IL-5, IL-13, IL-23a (Th2-driven), CXCL-13, CXCL-10 and CCL-5 (chemokines). This is the first study showing a direct linkage between the distribution pattern of immune cells in hypospermatogenesis versus testicular cancer and analysis of a wide range of 17 related cyto- and chemokines. A fundamental difference between testicular inflammation patterns associated with different testicular inflammatory conditions either containing or lacking neoplastic cells was demonstrated. In hypospermatogenesis, T cells were detected, whereas B cells and dendritic cells were almost absent. Within GCNIS and seminoma, in addition to T cells, high numbers of dendritic cells and B cells were found, the latter additionally organised in cell clusters, whereas mast cells were absent. Transcripts encoding pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), anti-inflammatory cytokines (TGF-β1), Th1-driven cytokines (IL-2 and IFN-γ) as well as chemokines (CXCL-13, CXCL-10 and CCL-5) were all significantly increased in testicular germ cell neoplasia (P ≤ 0.01), suggesting the presence of a pro-tumorigenic environment. In contrast, Th2-related cytokines (IL-5, IL-13 and IL-23a) characterised the environment within samples showing normal spermatogenesis as well as hypospermatogenesis. One of the most important outcomes is the pivotal role of IL-6 in testicular cancer that opens potential novel diagnostic and/or immune-therapeutic perspective for testis cancer. Testicular tissue composed of immune cells as well as other somatic cells and germ cells does not allow identification of specific cytokine sources or single cell types, being responsible for establishing the overall cytokine environment. In this study, laser-assisted microdissection did not reach the required efficiency for RT-qPCR analyses. Therefore, in vitro models would be suggested for addressing the above-mentioned issue. Conclusions about cytokine levels in testes with GCNIS are based on a

  5. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  6. A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Kit Curtius

    2015-05-01

    Full Text Available Barrett's esophagus (BE patients are routinely screened for high grade dysplasia (HGD and esophageal adenocarcinoma (EAC through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1 the probability that small cancers are missed during biopsy-based screening, (2 the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3 the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence.

  7. Levels of oxidative damage and lipid peroxidation in thyroid neoplasia.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    BACKGROUND: This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia. METHODS: Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue. RESULTS: Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status. CONCLUSION: High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.

  8. Scrotal neoplasia: would truck drivers be at greater risk?

    Directory of Open Access Journals (Sweden)

    Daniel Seabra

    2007-08-01

    Full Text Available OBJECTIVE: To analyze how scrotal neoplasias have been managed during the past decade and to question possible factors or professions associated to its presence. MATERIALS AND METHODS: We retrospectively evaluated every case reported from 1995 to 2005 at our hospital. We described the clinical scenario, complementary exams, treatments and outcomes. We also tried to verify if there was any risk, predisposing factors or professions that would explain the cancer origin. RESULTS: Six cases were reviewed. Out of these, three patients were truck drivers. Five of them showed restricted lesions without inguinal lymph nodes enlargement. Histologically, six patients presented squamous carcinoma, with two of them having the verrucous type. The median age of patients was 52 years old (31 to 89. The five patients who are still alive had their lesions completely removed with safety margin and primary closure. CONCLUSIONS: We have noticed that the scrotal carcinoma behavior is similar to that of the penis, where removal of the lesion and study of the regional lymph nodes help to increase the patient survival rate. The outstanding fact was that three out of six patients were truck drivers, raising the hypothesis that such profession, maybe due to the contact or attrition with the diesel exhaust expelled by the engine or to sexual promiscuity, would imply in a larger risk of developing this rare neoplasia.

  9. Dietary habits of colorectal neoplasia patients in comparison to their first-degree relatives.

    Science.gov (United States)

    Kajzrlikova, Ivana Mikoviny; Vitek, Petr; Chalupa, Josef; Dite, Petr

    2014-05-07

    To compare the dietary habits between colorectal neoplasia patients, their first-degree relatives, and unrelated controls. From July 2008 to April 2011, we collected epidemiological data relevant to colorectal cancer from patients with colorectal neoplasias, their first-degree relatives, and also from a control group consisting of people referred for colonoscopy with a negative family history of colorectal cancer and without evidence of neoplasia after colonoscopic examination. The first-degree relatives were divided into two groups following the colonoscopic examination: (1) patients with neoplasia or (2) patients without neoplasia. Dietary habits of all groups were compared. A χ (2) test was used to assess the association between two dichotomous categorical variables. The study groups consisted of 242 patients with colorectal neoplasias (143 men, 99 women; mean age: 64 ± 12 years) and 160 first-degree relatives (66 men, 94 women; mean age: 48 ± 11 years). Fifty-five of the first-degree relatives were found to have a neoplastic lesion upon colonoscopy, while the remaining 105 were without neoplasia. The control group contained 123 individuals with a negative family history for neoplastic lesions (66 men, 57 women; mean age: 54 ± 12 years). Two hypotheses were tested. In the first, the dietary habits of first-degree relatives with neoplasia were more similar to those of patients with neoplasia, while the dietary habits of first-degree relatives without neoplasia were similar to those of the control group. In the second, no sex-related differences in dietary habits were expected between the particular groups. Indeed, no significant differences were observed in the dietary habits between the groups of patients, controls and first-degree relatives with/without neoplastic lesions. Nevertheless, statistically significant sex-related differences were observed in all groups, wherein women had healthier dietary habits than men. In all groups examined, women had

  10. Ultrathin endoscopy versus high-resolution endoscopy for diagnosing superficial gastric neoplasia.

    Science.gov (United States)

    Toyoizumi, Hirobumi; Kaise, Mitsuru; Arakawa, Hiroshi; Yonezawa, Jin; Yoshida, Yukinaga; Kato, Masayuki; Yoshimura, Noboru; Goda, Ken-ichi; Tajiri, Hisao

    2009-08-01

    Ultrathin endoscopy (UTE) is an acceptable and cost-effective alternative to EGD with the patient under sedation, although the diagnostic accuracy of UTE is not well established. To compare the diagnostic accuracy of UTE and high-resolution endoscopy (HRE) for superficial gastric neoplasia. Prospective comparative study. Academic center. Patients with or without superficial gastric neoplasia underwent peroral UTE and HRE, back-to-back in a random order while under standard sedation. The procedures were performed by 2 endoscopists who were blinded to the clinical information. The rate of missed lesions and misdiagnosis, sensitivity, and specificity for the diagnosis of gastric neoplasia when using pathology as the reference standard. In total, 126 lesions (41 superficial gastric neoplasias, 85 nonneoplastic lesions) were recorded in 57 enrolled patients. For the diagnosis of gastric neoplasia, the sensitivity of UTE (58.5%) was significantly (P = .021) lower than that of HRE (78%), and the specificity of UTE (91.8%) was significantly (P = .014) lower than that of HRE (100%). The rate of missed lesions and misdiagnosis of gastric neoplasias when using UTE (41.5%) was significantly (P > .001) higher than that of HRE (22.0%). The corresponding rate of neoplasias at the proximal portion (fornix and corpus) when using UTE (29%) was significantly (P = .002) higher than that of HRE (7.2%), although the rates of neoplasias at the distal portion (angulus and antrum) were comparable for UTE and HRE. Small sample numbers in an enriched population. The diagnostic accuracy of UTE is significantly lower than that of HRE for superficial gastric neoplasia, and this difference is particularly striking for neoplasias in the proximal stomach. For UTE to be used as an alternative modality, improvements in optical quality and the incorporation of additional procedures, including close-range observations and chromoendoscopy, are required to enhance visualization.

  11. Pink-color sign in esophageal squamous neoplasia, and speculation regarding the underlying mechanism

    Science.gov (United States)

    Ishihara, Ryu; Kanzaki, Hiromitsu; Iishi, Hiroyasu; Nagai, Kengo; Matsui, Fumi; Yamashina, Takeshi; Matsuura, Noriko; Ito, Takashi; Fujii, Mototsugu; Yamamoto, Sachiko; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Tomita, Yasuhiko; Ishiguro, Shingo

    2013-01-01

    AIM: To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions. METHODS: In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pink-color sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed. RESULTS: A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range: 2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0

  12. 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

  13. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

    International Nuclear Information System (INIS)

    O'Brien, R.T.; Evans, S.M.; Wortman, J.A.; Hendrick, M.J.

    1996-01-01

    Objective: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Design: Retrospective study. Animals: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Procedure: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Results: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Clinical Implications: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia

  14. Metastização pulmonar de neoplasia da mama

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    Jorge Dionísio

    2002-03-01

    Full Text Available RESUMO: Para caracterizar os doentes com metastização pulmonar de neoplasia da mama, procedemos a um estudo retrospectivo dos processos de 129 doentes referenciados à Unidade de Pneumologia entre Julho de 1990 e Janeiro de 2000.Foi considerada a existência de metastização pulmonar em 89 casos.Avaliámos as manifestações clínicas apresentadas, o intervalo de tempo até ao diagnóstico de metastização pulmonar, os aspectos radiológicos, endoscópicos, as terapêuticas efectuadas e a sobrevida.O intervalo médio entre o diagnóstico da neoplasia da mama e o diagnóstico de metastização pulmonar foi de 81,9±5,7 meses. Os sintomas respiratórios foram referidos em 83,1% dos doentes. O padrão radiológico mais comum foi a presença de massas ou nódulos pulmonares (66,3%. Foram observadas 49 com sinais directos de neoplasia na broncofibroscopia. Em 47 os aspectos anatomopatológicos encontrados foram compatíveis com metastização endobrônquica de tumor da mamaO tratamento mais frequentemente utilizado após o diagnóstico de metástase pulmonar foi a quimioterapia, em 60,2% dos casos.Após o diagnóstico de metastização, a sobrevida mediana foi de 20,1 meses, com 63,4% dos doentes vivos ao fim de 1 ano.Nos doentes com carcinoma da mama e suspeita de metastização verificámos um grande intervalo livre entre o diagnóstico do tumor da mama e o aparecimento de metastização. Os sintomas respiratórios tra-duziram a grande frequência de envolvimento endobrônquico. O diagnóstico anatomopatológico de metastização pulmonar foi obtido em 52,8% dos doentes. A terapêutica mais utilizada após diagnóstico de metastização foi a quimioterapia e a sobrevida ao ano foi de 63,4%.REV PORT PNEUMOL 2002; VIII (2: ABSTRACT: We performed a retrospective study of 129 patients observed in Pneumology unit between July 1990 and January 2000 to evaluate the clinical, radiological and endoscopic patterns as well as the clinical evolution of

  15. Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis).

    Science.gov (United States)

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

    2018-02-01

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

  16. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Directory of Open Access Journals (Sweden)

    Grzegorz Piecha

    2010-01-01

    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  17. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  18. Manejo de las adolescentes con neoplasia intraepitelial cervical

    OpenAIRE

    Martínez Chang, Ysis Margarita; Sarduy Nápoles, Miguel

    2006-01-01

    Se realizó un estudio descriptivo en pacientes adolescentes que acudieron a la consulta de patología de cuello del Hospital “Ramón González Coro” en el período comprendido de enero de 2003 a mayo de 2005. El número de pacientes atendidas ascendió a 144 y de ellas 32 presentaron neoplasia intraepitelial cervical. El grupo de edades más frecuente resultó el comprendido entre 17 y 18 años, con una frecuencia referida entre 2 y 3 parejas sexuales. La infección de transmisión sexual más común fue ...

  19. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

    1987-01-01

    The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently

  20. Advanced colorectal neoplasia risk stratification by penalized logistic regression.

    Science.gov (United States)

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

    2016-08-01

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

  1. Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

    Science.gov (United States)

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

    2015-01-01

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

  2. Neoplasias de Cavidad nasal y senos paranasales en caninos

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    Giovanni Torres

    2008-10-01

    Full Text Available Las neoplasias de cavidad nasal y senos paranasales en caninos son de escasa presentación; llegan tan sóloal 1.5% de los quistes diagnosticados en esta especie.Con referencia al total de tumores del tracto respiratorio representan entre el 60 y el 80%. Son más comunes en caninos de nariz larga, no existe predilección por género; por el comportamiento, las neoplasias que se desarrollanen la cavidad nasal y senos paranasales son benignas y malignas, siendo estas últimas las más frecuentes. Teniendo en cuenta el tejido de origen pueden ser epiteliales, mesenquimales y de otro origen como los linfomas y el tumor venéreo transmisible. La apariciónde la sintomatología se asocia con la capacidad de obstruir las vías aéreas, la invasión y destrucción local de tejido. En general los signos clínicos asociados consistenen: dificultad respiratoria, estornudo, secreciónnasal, hemorragia nasal y la presencia de masas de características variadas en tamaño y forma. El diagnóstico se basa en signos clínicos, evaluación citológica e histológica de las lesiones. Esta última es 100% diagnóstica, para el tratamiento se utiliza la extracción quirúrgica combinada con terapia de radiación y quimioterapia.

  3. 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.

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

    Science.gov (United States)

    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.

  5. Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project

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    Herrero Rolando

    1997-01-01

    Full Text Available This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10 738 women who were eligible to participate, 10 049 (93.6% were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL. Details of the field operation are outlined, with particular reference to the

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

    Directory of Open Access Journals (Sweden)

    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.

  7. The Relationship Between Distal and Proximal Colonic Neoplasia : A Meta-Analysis

    NARCIS (Netherlands)

    Dodou, D.; De Winter, J.C.F.

    2011-01-01

    To investigate the association between proximal colonic neoplasia and distal lesions as a function of the lesion type. The extent to which health, demographic, and study characteristics moderate this association was also examined.

  8. Diagnosing Cervical Neoplasia in Rural Brazil Using a Mobile Van Equipped with In Vivo Microscopy: A Cluster-Randomized Community Trial.

    Science.gov (United States)

    Hunt, Brady; Fregnani, José Humberto Tavares Guerreiro; Schwarz, Richard A; Pantano, Naitielle; Tesoni, Suelen; Possati-Resende, Júlio César; Antoniazzi, Marcio; de Oliveira Fonseca, Bruno; de Macêdo Matsushita, Graziela; Scapulatempo-Neto, Cristovam; Kerr, Ligia; Castle, Philip E; Schmeler, Kathleen; Richards-Kortum, Rebecca

    2018-06-01

    Cervical cancer is a leading cause of death in underserved areas of Brazil. This prospective randomized trial involved 200 women in southern/central Brazil with abnormal Papanicolaou tests. Participants were randomized by geographic cluster and referred for diagnostic evaluation either at a mobile van upon its scheduled visit to their local community, or at a central hospital. Participants in both arms underwent colposcopy, in vivo microscopy, and cervical biopsies. We compared rates of diagnostic follow-up completion between study arms, and also evaluated the diagnostic performance of in vivo microscopy compared with colposcopy. There was a 23% absolute and 37% relative increase in diagnostic follow-up completion rates for patients referred to the mobile van (102/117, 87%) compared with the central hospital (53/83, 64%; P = 0.0001; risk ratio = 1.37, 95% CI, 1.14-1.63). In 229 cervical sites in 144 patients, colposcopic examination identified sites diagnosed as cervical intraepithelial neoplasia grade 2 or more severe (CIN2+; 85 sites) with a sensitivity of 94% (95% CI, 87%-98%) and specificity of 50% (95% CI, 42%-58%). In vivo microscopy with real-time automated image analysis identified CIN2+ with a sensitivity of 92% (95% CI, 84%-97%) and specificity of 48% (95% CI, 40%-56%). Women referred to the mobile van were more likely to complete their diagnostic follow-up compared with those referred to a central hospital, without compromise in clinical care. In vivo microscopy in a mobile van provides automated diagnostic imaging with sensitivity and specificity similar to colposcopy. Cancer Prev Res; 11(6); 359-70. ©2018 AACR . ©2018 American Association for Cancer Research.

  9. Deregulated TNF-Alpha Levels Along with HPV Genotype 16 Infection Are Associated with Pathogenesis of Cervical Neoplasia in Northeast Indian Patients.

    Science.gov (United States)

    Das, Chandana Ray; Tiwari, Diptika; Dongre, Anita; Khan, Mohammad Aasif; Husain, Syed Akhtar; Sarma, Anirudha; Bose, Sujoy; Bose, Purabi Deka

    2018-05-01

    Multiple factors are associated with human papillomavirus (HPV) infection related cervical anomalies and its progression to cervical carcinoma (CaCx), but data vary with respect to the underlying HPV genotype and with population being studied. No data are available regarding the role of immunological imbalance in HPV infected CaCx pathogenesis from Northeast India, which has an ethnically distinct population, and was aimed to be addressed through this study. The study included 76 CaCx cases, 25 cervical intraepithelial neoplasia (CIN) cases, and 50 healthy female controls. HPV screening and genotyping were performed by PCR. Differential expression of tumor necrosis factor alpha (TNF-α) was studied at serum level by enzyme-linked immunosorbent assay and tissue level by immunohistochemistry and messenger RNA (mRNA) level by real-time PCR. The data were correlated with interferon gamma (IFN-γ) and NF-κβp65 levels at protein level, as well as HPV16 E6 and E7 expression at transcript level statistically. HPV infection and HPV16 genotype were predominant in the studied cohort. TNF-α was found to be downregulated at both mRNA and protein levels in CaCx cases compared to controls; and the gradient downregulation correlated with progression of the disease from normal→CIN→CaCx. TNF-α expression correlated with insufficient modulation of both IFN-γ and NF-κβp65. The HPV16 E6 and E7 transcripts were found to be sharply upregulated in CaCx cases strongly inversely correlated with the TNF-α expression. Significant role of TNF-α downregulation associated with insufficient IFN-γ and total NF-κβp65 modulation and the resulting significant upregulation of viral transcripts E6 and E7 are key to the HPV16 infection mediated CaCx pathogenesis in northeast Indian patients.

  10. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

  13. 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.

  14. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

    Science.gov (United States)

    Park, Youn Su; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Lee, Jae Kyung; Kim, Joo Sung; Koh, Seong-Joon

    2017-04-01

    Although sarcopenia is associated with an increased risk for mortality after the curative resection of colorectal cancer, its influence on the development of advanced colonic neoplasia remains unclear. This study included 1270 subjects aged 40 years or older evaluated with first-time screening colonoscopy at Seoul National University Boramae Health Care Center from January 2010 to February 2015. Skeletal muscle mass was measured with a body composition analyzer (direct segmental multifrequency bioelectrical impedance analysis method). Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with advanced colorectal neoplasia. Of 1270 subjects, 139 (10.9%) were categorized into the sarcopenia group and 1131 (89.1%) into the non-sarcopenia group. In the non-sarcopenia group, 55 subjects (4.9%) had advanced colorectal neoplasia. However, in the sarcopenia group, 19 subjects (13.7%) had advanced colorectal neoplasia, including 1 subject with invasive colorectal cancer (0.7%). In addition, subjects with sarcopenia had a higher prevalence of advanced adenoma (P sarcopenia. According to the multiple logistic regression analysis adjusted for variable confounders, age (odds ratio 1.062, 95% confidence interval 1.032-1.093; P sarcopenia (odds ratio 2.347, 95% confidence interval 1.311-4.202; P = 0.004) were associated with an advanced colorectal neoplasia. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

  15. Tuberculose ileocecal isolada simulando neoplasia maligna e doença de Crohn Isolated ileocecal tuberculosis simulating malignant neoplasia and Crohn's disease

    Directory of Open Access Journals (Sweden)

    S.H. BROMBERG

    2001-06-01

    Full Text Available OBJETIVO: No Brasil, a tuberculose ileocecal isolada, na ausência de tuberculose pulmonar ativa ou cicatrizada, é rara, sendo freqüentemente confundida com neoplasia e a doença de Crohn. MÉTODOS: Os autores apresentam oito doentes com essas características, tratados por cirurgia, em período de 20 anos. A dor abdominal na fossa ilíaca direita foi o principal sintoma (100%, seguido da presença de perda de peso (62,5%, febre, náuseas e vômitos e fadiga em 50% dos doentes. Sete enfermos (87,5% apresentaram massa palpável na fossa ilíaca direita. A duração média dos sintomas foi de 14,7 meses, variando de 5 a 36 meses. Todas as lesões foram detectadas pelo enema opaco e mimetizavam aspecto neoplásico. A colonoscopia foi realizada em três doentes, evidenciando lesões sub-oclusivas da região íleo-cecal em dois; as biópsias foram sugestivas de tuberculose, não sendo possível diferenciá-las da doença de Crohn. RESULTADOS: Seis enfermos com diagnóstico presuntivo de neoplasia foram submetidos a cirurgia eletiva, realizando-se neles a colectomia direita clássica. Os outros dois, com suspeita de tuberculose, foram operados na vigência de obstrução intestinal, sendo submetidos a ressecção limitada (ileocecectomia. O estudo anatomopatológico estabeleceu o diagnóstico final pelo encontro de necrose caseosa e de bacilos álcool ácido-resistentes no intestino ou nos linfonodos. A evolução pós-operatória foi satisfatória, com pequena morbidade resolvida clinicamente. Posteriormente, todos os doentes receberam o esquema tríplice por 12 meses, variando a droga de acordo com a época do tratamento. CONCLUSÃO: Apesar de rara, a tuberculose hipertrófica ileocecal isolada freqüentemente é confundida com neoplasias e com a doença de Crohn, devendo ser lembrada no diagnóstico diferencial das lesões localizadas no quadrante inferior direito do abdome.BACKGROUND: Isolated ileocecal involvement by tuberculosis in the absence

  16. Normal villous architecture with increased intraepithelial lymphocytes: a duodenal manifestation of Crohn disease.

    Science.gov (United States)

    Patterson, Emily R; Shmidt, Eugenia; Oxentenko, Amy S; Enders, Felicity T; Smyrk, Thomas C

    2015-03-01

    To assess a possible association between inflammatory bowel disease (IBD) and the histologic finding in duodenal biopsy specimens of increased intraepithelial lymphocytes (IELs) with normal villous architecture. We identified all patients with duodenal biopsy specimens obtained between 2000 and 2010 showing increased IELs and normal architecture. Among the 74 such patients who also had IBD, we characterized the clinical features of IBD and reviewed all available upper gastrointestinal biopsy specimens. Fifty-eight patients had Crohn disease, 13 had ulcerative colitis, and three had IBD, type unclassified. No duodenal sample with increased IELs had other histologic features of IBD. Among gastric biopsy specimens from 34 patients with Crohn disease, nearly half (16) had focal gastritis. We propose that Crohn disease be included in the differential diagnosis for increased IELs with normal villous architecture in duodenal biopsy specimens, particularly when gastric biopsy specimens show focal gastritis. Copyright© by the American Society for Clinical Pathology.

  17. Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

    Science.gov (United States)

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

    2016-07-03

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

  18. Gestational trophoblastic neoplasia: efficacy of color doppler ultrasound

    International Nuclear Information System (INIS)

    Song, Sun Wha; Jee, Won Hee; Choe, Bo Young; Byun, Jae Young; Choi, Byung Gil; Shinn, Kyung Sub

    1997-01-01

    To evaluate the efficacy of color Doppler ultrasound (US) in the diagnosis of gestational trophoblastic neoplasia (GTN). Intralesional color flows and resistive index (RI) on color Doppler US were prospectively analyzed in 21 consecutive suspected GTN cases. RI of the intralesional artery was investigated on the basis of the presence or absence of mass and metastasis. Correlation between RI of intralesional artery and urinary β-hCG was also investigated. Intralesional color flows were identified in 15 patients with GTN. On operation, intralesional color flows were observed in one of two patients in whom the presence of completely necrotic tissue was confirmed. Intralesional color flows, however, were not detected in four patients who were proved not to be GTN sufferers. Sensitivity, specificity, accuracy, positive and negative predictive values, and accuracy were 100%, 83%, 95%, 94% and 100%, respectively. Significant correlation between RI of the intralesional artery and urinary β-hCG was not established (p=0.49, r=0.19). RI of this artery was not substantially different between groups with and without mass, and between groups with and without metastasis (p=0.32, p=0.82). The current study demonstrates that color Doppler US is a sensitive and useful method for the diagnosis of GTN

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

    Science.gov (United States)

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

    2016-01-01

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

  20. INFECTION WITH HUMAN PAPILLOMA VIRUS IN CERVICAL NEOPLASIA

    Directory of Open Access Journals (Sweden)

    Eduard Crauciuc

    2010-09-01

    Full Text Available The purpose of this study was to establish if the infection with human papilloma virus (HPV presents a potential irreversible evolution towards malignancy. Materials and methods. The study was made on a number of 1885 patients that were suspected to have cervical neoplasia, which were monitored between 2001-2010 in „Elena-Doamna” Clinical Hospital of Obstetrics and Gynecology in Ia�i, the Military Hospital Gala�i, the County Hospital Gala�i and the Emergency Hospital Buzau. Results and discussions. The study proved that the risk of contacting a genital infection with HPV and cervical cancer is influenced by the sexual activity, the risk of getting infected with HPV during a person’ s lifetime is at least 50% for those sexually active. Conclusions. The patients benefited from colposcopy and biopsy only if the repeated cytology suggested more severe changes. The conservative conduct is represented by a repeated cytology when the patients are admitted into the lot (the initial cytology is performed before this moment

  1. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout

    International Nuclear Information System (INIS)

    Hamilton, T.E.; van Belle, G.; LoGerfo, J.P.

    1987-01-01

    We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship

  2. Altered Peptidase Activities in Thyroid Neoplasia and Hyperplasia

    Directory of Open Access Journals (Sweden)

    Gorka Larrinaga

    2013-01-01

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

  3. Altered peptidase activities in thyroid neoplasia and hyperplasia.

    Science.gov (United States)

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

    2013-01-01

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

  4. Predictors of advanced colorectal neoplasia for colorectal cancer screening.

    Science.gov (United States)

    Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y

    2014-05-01

    The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, pstatistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.

  5. Problems in distinguishing spinal tuberculosis from neoplasia on MRI

    International Nuclear Information System (INIS)

    Gupta, R.K.; Agarwal, P.; Rastogi, H.; Kumar, S.; Phadke, R.V.; Krishnani, N.

    1996-01-01

    We reviewed MRI studies of 60 patients presenting with extradural compressive myeloradiculopathy secondary to vertebral disease to assess the imaging features which may help in differentiating tuberculous from neoplastic disease. Spin-echo T1-, proton density- and T2-weighted images were available for all patients and fast low-angle shot images with a low flip angle for 21 patients. Contrast-enhanced images were available for 28 patients. There were 41 patients with tuberculosis and 19 patients with neoplastic disease (metastases 11, lymphoma 6, plasmacytoma 1, and giant cell tumour 1). Discovertebral disease with or without involvement of the posterior arch was a feature not only of tuberculous spondylitis (30 patients) but also of metastases (6). The remaining 11 patients with tuberculosis had ''atypical'' involvement (vertebral body with or without posterior arch in 8 and posterior arch alone in 3) described as typical of neoplasms. This ''typical'' involvement was seen in metastases (5), lymphoma (6) and the 2 primary bone tumours. The presence of an abscess helped in differentiating tuberculosis from neoplasia in 22 of the 41 patients with tuberculosis and was absent in all with neoplasms. The presence of bone fragments in 16 patients (8 with and 8 without an abscess) was found to be specific for tuberculosis. In the absence of an abscess or bone fragments, image-guided biopsy is essential to establish the diagnosis. (orig.). With 9 figs., 2 tabs

  6. Neoplasias endocrinas múltiples. desde el laboratorio al paciente

    Directory of Open Access Journals (Sweden)

    Dr. G. Nelson Wohllk

    2013-09-01

    Full Text Available Las neoplasias endocrinas múltiples (NEM tipo 1 y 2 son enfermedades genéticas heredadas en forma autosómica dominante. Las principales manifestaciones clínicas en NEM1 incluyen tumores paratiroideos, hipofisiarios y gastroenteropancreáticos. El test genético se puede realizar en los pacientes y potenciales portadores de mutaciones en el gen menin, pero la correlación genotipo-fenotipo es menos directa en comparación a NEM2. En la NEM2 el cáncer medular de tíroides (CMT es común a los tres subtipos: NEM2A (feocromocitoma e hiperparatiroidismo, NEM2B (feocromocitoma y neuromas mucosos y CMT familiar. A aquellos pacientes con mutación RET se les debe recomendar la realización de tiroidectomía profiláctica en la niñez, de acuerdo a la categoría de riesgo ATA. Algunos casos de CMT aparentemente esporádicos son actualmente NEM2 después de la realización del estudio genético para proto-oncogen RET, por lo tanto se recomienda la aplicación rutinaria de este estudio a todos los pacientes con CMT aparentemente esporádico.

  7. 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...

  8. Lobular neoplasia - borderline type of lesion - risk of subsequent development of invasive lobular carcinoma of the breast, 13 years after excision of radial scar with multifocal lobular neoplasia

    International Nuclear Information System (INIS)

    Wardzynska, K.; Wesolowska, E.; Baranska, J.

    2010-01-01

    Background. Lobular neoplasia is a hyperplastic breast lesion - a borderline type of lesion with a high risk of subsequent development of invasive carcinoma. In case of radial scar diagnosis the risk of invasive carcinoma increases twice in comparison with healthy patients population while in the case of lobular neoplasia diagnosis within radial scar this risk increases 8 to 10 times. Basing on the presented case we analyse and review the literature regarding the clinical, radiological and pathological aspects of lobular neoplasia of the breast. Case report. A 67-yeas old patient was hospitalised in 1995 in order to consult the results of mammography, which revealed a radial scar lesion of the right breast. The patient was then referred to undergo wide local excision. Pathological examination showed dysplastic changes of the radial scar type with 1 cm multifocal lobular neoplasia. The patient was systematically followed clinically and radiologically during the decade 1996-2006 and all examination results were normal. In 2008, an ill-defined nodule appeared within the scar on mammography examination. This was categorized as BI-RADS 4C. The mammotomic biopsy performed under ultrasonography control revealed invasive lobular carcinoma. The tumor was totally locally excised and the sentinel node was histologically verified. The histopathological examination revealed a 1.6 cm focus of invasive lobular carcinoma and the sentinel node was negative. Conclusion. Patients with detected lobular neoplasia should be treated as a risk group of invasive breast cancer development (30-40% vs 10% in a healthy population during the entire life period). Systematic clinical and radiological follow-up should be mandatory. (authors)

  9. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Directory of Open Access Journals (Sweden)

    Nagayasu Egawa

    2015-07-01

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

  10. Multiple endocrine neoplasia detection on I-123 MIBG imaging

    International Nuclear Information System (INIS)

    Reinhardt, C.A.; McEwan, L.M.; Wong, J.C.H.

    2000-01-01

    Full text: An 123 I meta-iodobenzylguanidine (MIBG) scan was performed on a 54-year-old lady with familial phaeochromocytoma, to evaluate for bilateral or extra-adrenal disease. She has hypertension with raised catecholamines and CT evidence of a right adrenal phaeochromocytoma, and a female sibling with bilateral phaeochromocytoma. Thyroid blockade using Lugol's Iodine was given orally prior to intravenous administration of 370 MBq 123 I MIBG. Planar and SPECT imaging were acquired at 24 hours. There was intense uptake in the known right phaeochromocytoma. An unexpected finding was focal intense uptake in the region of the right thyroid lobe, which may be either a functioning paraganglioma arising from the cervical sympathetic ganglia or a medullary thyroid carcinoma (MTC). At 48 hours, a further image of the neck showed no changes. This was followed by a standard injection of 150 MBq 99 Tc m pertechnetate for thyroid scanning. Imaging obtained on 99 Tc m energy window setting showed a large hypofunctioning region in the right thyroid lobe, corresponding in location to the focal 123 I MIBG uptake. This is in keeping with a MTC, a neuroendocrine tumour, as other thyroid carcinomas are non-MIBG avid. A subsequent serum calcitonin assay showed elevated levels. The patient underwent surgical removal of the right phaeochromocytoma followed several weeks later by a right hemithyroidectomy. Histological reports confirmed the tumour diagnoses. The patient's familial phaeochromocytoma is therefore part of the multiple endocrine neoplasia syndrome Type 2A (MEN 2A). To date, biochemistry has not shown any evidence of hyperparathyroidism which occurs in 15-20 per cent of patients with MEN 2A. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  11. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Science.gov (United States)

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

    2015-01-01

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

  12. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    Science.gov (United States)

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

    Science.gov (United States)

    Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

    2015-09-01

    To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. [Serrated polyps and their association with synchronous advanced colorectal neoplasia].

    Science.gov (United States)

    Urman, Jesús; Gomez, Marta; Basterra, Marta; Mercado, María Del Rosario; Montes, Marta; Gómez Dorronsoro, Marisa; Garaigorta, Maitane; Fraile, María; Rubio, Eva; Aisa, Gregorio; Galbete, Arkaitz

    2016-11-01

    Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. A cross-sectional population-based study in all patients (1,538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analyzed. One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77-3.21] and OR: 2.29 [1.72-3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous ACN. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

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

    Science.gov (United States)

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

    2018-03-17

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

  16. Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Paul J Leo

    2017-08-01

    Full Text Available A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4% of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

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

    Science.gov (United States)

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

    2017-01-15

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

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

    Science.gov (United States)

    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.

  19. Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum

    Science.gov (United States)

    Montalvillo, Enrique; Bernardo, David; Martínez-Abad, Beatriz; Allegretti, Yessica; Fernández-Salazar, Luis; Calvo, Carmen; Chirdo, Fernando G.; Garrote, José A.; Arranz, Eduardo

    2015-01-01

    Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum. PMID:26529008

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

    Science.gov (United States)

    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

  1. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    Science.gov (United States)

    ... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

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

    Science.gov (United States)

    Sharma, Anjana; Panda, Anita

    2007-01-01

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

  3. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    International Nuclear Information System (INIS)

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-01-01

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferatio