Une nouvelle Classification des néoptasies intraépithélates vulvaires [A new classification of vulvar intraepithelial neoplasia (VIN)]

Vulvar cancer is a rare disease and its screening is depending on the quality and the relevance of our clinical examination. Incidence of vulvar cancer and especially precancerous lesions, vulvar intraepithelial neoplasias (VIN), increased during these last years. The new terminology of vulvar intraepithelial neoplasia will help us to identify high risk groups which could develop a cancer: usual and differentiated VIN. An early diagnosis is essential to propose an adequate treatment. Management is a major point according to the rising incidence of these lesions in younger women. Until we can observe a benefit from the vaccination against human papillomavirus, we must increase the quality of screening by a careful examination of the vulva.

Aspectos ultra-sonográficos da neoplasia epitelial papilífera sólido-cística do pâncreas

Os autores relatam os aspectos clínicos, macroscópicos e ultra-sonográficos em 11 pacientes com neoplasia epitelial papilífera sólido-cística (NEPSC) de pâncreas avaliados prospectivamente. Dez pacientes eram do sexo feminino e um era do sexo masculino, com idades entre 15 e 75 anos (média de 27 anos). Todos os pacientes tiveram diagnóstico de NEPSC de pâncreas comprovado por exame histopatológico e foram submetidos a exames de ultra-sonografia no pré-operatório. Foram avaliadas as dimensões, a localização e os aspectos ultra-sonográficos dos tumores, realizando-se correlação com suas características macroscópicas. O diâmetro transverso médio das lesões foi de 8,7 cm (variação: 4,2 a 16,0 cm). Três localizavam-se na cabeça, três no corpo e cinco na cauda do pâncreas. Todas as lesões tinham algum grau de hemorragia intratumoral e eram bem delimitadas e encapsuladas. Em todos os casos houve correlação completa entre o aspecto macroscópico dos tumores com os achados da ultra-sonografia. Os tumores eram predominantemente sólidos em três casos (27,3%), císticos em um (9,1%) e com aspecto sólido-cístico em sete (63,6%). Foram identificadas calcificações, predominantemente periféricas, em quatro (36,4%) dos 11 pacientes. Todos os tumores estabeleciam contato com algum segmento do eixo venoso espleno-mesentérico-portal. Em apenas um caso foi confirmada invasão vascular tumoral. Não foram identificadas metástases ganglionares ou a distância em nenhum paciente. Os autores concluem que as características ultra-sonográficas se correlacionaram com os aspectos macroscópicos das lesões em todos os casos, e que, embora não-específicas, elas são bastante sugestivas do diagnóstico de NEPSC se analisadas no contexto clínico apropriado.

Neoplasia intraepitelial vulvar: um problema atual

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.

Human papillomavirus infection and p53 protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma

The etiopathogenesis of vulvar intraepithelial neoplasia (VIN III) and invasive squamous cell carcinoma are largely unknown. Since there are few studies on Brazilian patients, our purpose was to determine the frequency of human papillomavirus (HPV) infection and the expression of p53 in these lesions, and associate them with other factors such as age, morphological subtypes, multicentric and multifocal disease. Thirty-eight cases of VIN III, nine of superficially invasive carcinoma, and 55 of invasive vulvar carcinoma were retrospectively evaluated from 1983 to 1995 for the presence of HPV by immunohistochemistry and in situ hybridization, and for p53 protein expression by immunohistochemistry on paraffin sections. All cases for whom material (slides and paraffin blocks) and clinical data were available were included. HPV and p53 were detected in 57.9 and 21.1% of the VIN III lesions, 33.3 and 66.7% of superficially invasive carcinomas, and 7.3 and 58.2% of invasive squamous cell carcinomas, respectively. HPV infection was associated with younger age in the VIN III and invasive carcinoma groups. In the latter, HPV infection was associated with the basaloid variant. p53 expression rate was higher in superficially invasive and invasive lesions and was not related to HPV infection. Our findings are similar to others and support the hypothesis that there are two separate entities of the disease, one associated with HPV and the other unrelated, with p53 inactivation possibly being implicated in some of the cases.

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

Objectives: 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). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.

Development of a postsurgical patient-reported outcome instrument for women with vulvar neoplasia

To (a) develop the Women With Vulvar Neoplasia-Patient-Reported Outcome (WOMAN-PRO) instrument as a measure of women's post-vulvar surgery symptom experience and informational needs, (b) examine its content validity, (c) describe modifications based on pilot testing, and (d) examine the content validity of the revised instrument.

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.

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study.

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.

Claudin and p53 expression in vulvar lichen sclerosus and squamous-cell carcinoma

Aims Vulvar squamous-cell carcinoma (SCC) is a rare gynaecological cancer. Vulvar SCC has been shown to develop from vulvar intraepithelial neoplasias, which are related to lichen sclerosus (LS). Most studies to date have compared vulvar SCC with LS only morphologically, but no detailed molecular analysis has been performed. The objective was to compare claudin and p53 expression in these diseases and determine if there was any association with expression and vulvar SCC progression. Methods Immunohistochemical analysis was performed in order to determine expression of p53 and claudin 1, 2, 3, 4, 5, 7 and 11 in human vulvar tissue samples from LS, SCC and control patients. Results Claudin 1, 2, 3, 4 and 5 were expressed comparably in the three groups. Claudin 7 and 11 expression was significantly decreased in LS and SCC samples compared with the control group. Expression of p53 was significantly increased in SCC and LS patient samples compared with the control group. Conclusions Claudin 7 and 11 were not expressed in LS and SCC. However, there was no significant difference in expression of any of the claudins between the LS and SCC samples. Furthermore, p53 expression is the highest in SCC patients and lowest in the control group. However, expression of p53 did not vary between samples from isolated LS and LS associated SCC patients, suggesting that increased p53 expression is not the determining factor in the progression of LS lesions to SCC.

Trombo Livre Intra-Auricular Direito e Embolia Pulmonar

Os autores descrevem um caso de um doente com uma neoplasia da bexiga inoperável, internado por um quadro de síncope e hipotensão arterial. Na avaliação do doente é efectuado um ecocardiograma que mostra a existência de um trombo livre ao nível das cavidades direitas e dilatação das mesmas que levou à hipótese diagnóstica de embolia pulmonar. Perante a existência de uma neoplasia com hemorragia recente, algumas dúvidas terapêuticas surgiram, tendo sido iniciado heparina. Devido a agravamento da situação, com hipertensão pulmonar grave e presença de volumosos trombos ao nível de ambos os ramos da artéria pulmonar visualizados por ecocardiografia transesofágica, o doente acabou por ser submetido a trombólise, embora com algumas alterações ao esquema habitualmente realizado. O doente melhorou, sendo o ecocardiograma final normal.

Fístula pancreática após duodenopancreatectomia: correlação dos aspectos intra-operatórios e histologicos do pâncreas

OBJETIVO: Avaliar a relação entre a ocorrência de fístula pancreática pós-anastomose pancreatojejunal, em doentes submetidos à duodenopancreatectomia por neoplasia maligna periampolar, com aspectos histológicos de fibrose e inflamação encontrados no tecido pancreático e com o calibre do ducto pancreático principal. MÉTODOS: Estudo retrospectivo interessando doentes que foram submetidos ao tratamento com ressecção cirúrgica. Verificou-se o índice de fístulas pancreáticas encontradas. Classificou-se de acordo com a histologia da fibrose e da inflamação pancreática. RESULTADOS: Identificaram-se 77 doentes, com média de idade de 57,6 anos, sendo 62,4% do sexo masculino. De acordo com o tipo de operação realizada, 66,3% constituíram-se em gastroduodenopancreatectomia e 33,7% em duodenopancreatectomia com preservação do piloro. Em relação ao número de fístulas diagnosticadas, identificou-se que 23,4% doentes apresentaram tal complicação pós-operatória, sendo que em 66,7% a causa era neoplasia de papila. Achados macroscópicos intraoperatórios, identificou-se classificação da textura pancreática, tida como normal, em 85,8% e, quanto ao calibre do ducto principal pancreático, foi encontrada média de 4,9mm. Houve relação importante entre a consistência endurecida do coto pancreático e a ausência da fístula. Nos doentes com tecido normal ou amolecido, o índice de fístula foi 25,4%. Quanto ao diâmetro ductal, identificou-se (p <0,05) maior número de deiscências da anastomose pancreática na ausência de dilatação ductal. Evidenciou-se que doentes com valores médios do diâmetro de ducto de 5,4mm (76,7%) não mostraram esta complicação. CONCLUSÃO: A presença de fibrose e de dilatação ductal habitualmente coexistem e estão relacionadas à menor porcentagem de fístulas enteropancreáticas.

Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: Retrospective pooled analysis of trial data

Objectives To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk of developing subsequent disease after an excisional procedure for cervical intraepithelial neoplasia or diagnosis of genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia. Design Retrospective analysis of data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). Setting Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants Among 17 622 women aged 15–26 years who underwent 1:1 randomisation to vaccine or placebo, 2054 received cervical surgery or were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia. Intervention Three doses of quadrivalent HPV vaccine or placebo at day 1, month 2, and month 6. Main outcome measures Incidence of HPV related disease from 60 days after treatment or diagnosis, expressed as the number of women with an end point per 100 person years at risk. Results A total of 587 vaccine and 763 placebo recipients underwent cervical surgery. The incidence of any subsequent HPV related disease was 6.6 and 12.2 in vaccine and placebo recipients respectively (46.2% reduction (95% confidence interval 22.5% to 63.2%) with vaccination). Vaccination was associated with a significant reduction in risk of any subsequent high grade disease of the cervix by 64.9% (20.1% to 86.3%). A total of 229 vaccine recipients and 475 placebo recipients were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia, and the incidence of any subsequent HPV related disease was 20.1 and 31.0 in vaccine and placebo recipients respectively (35.2% reduction (13.8% to 51.8%)). Conclusions Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease.

Linfadenectomia laparoscópica em cadela com neoplasia mamária

A linfadenectomia laparoscópica é realizada de forma rotineira na medicina, contudo é pouco utilizada na veterinária. Neste relato, um canino fêmea apresentando tumores na cadeia mamária esquerda (M4 e M5), foi submetido à aplicação intradérmica do azul de metileno estéril, ao redor do maior tumor (M5), buscando-se demarcação dos vasos linfáticos e linfonodos regionais. Após 15 minutos, iniciou-se a linfadenectomia abdominal videolaparoscópica na região inguinal esquerda, seguida da ovário-histerectomia (OVH) lapararoscópica com três portais. Realizou-se ainda mastectomia total unilateral esquerda. Pela histologia, obtiveram-se dois linfonodos abdominais livres de células tumorais. A paciente não apresentou recidiva em 60 dias.

Avaliação de quimiocinas séricas em mulheres com câncer epitelial de ovário

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Estudo da resposta imune humoral em mulheres com neoplasia ovariana. -

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB