Variação na detecção do DNA-HPV de alto risco oncogenico no seguimento de mulheres portadoras de neoplasia intra-epitelial cervical tratadas com conização por alça diatermica

Orientador: Sophie Françoise Mauricette DerchainDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Objetivo: Avaliar a variação na detecção do Papiloma vírus humano (HPV) de alto risco oncogênico através da Captura de Híbridos II (CHII) e seu valor como fator preditivo de persistência ou recidiva de neoplasia intra-epitelial cervical (NIC) grau 2 ou 3 no seguimento de mulheres portadoras de lesões de alto grau, tratadas com conização por alça diatérmica. Sujeitos e métodos: Estudo clínico de coorte em que foram avaliadas 94 mulheres submetidas a conização por alça diatérmica entre março de 2001 e setembro de 2002 no ambulatório de Patologia Cervical do CAISM-UNICAMP. Foram incluídas apenas mulheres com, no mínimo, um retorno em 6 ou 12 meses após a cirurgia, em cujos espécimes cirúrgicos tenha sido encontrado NIC 2 ou NIC 3. Foram agendados retornos em 6 e 12 meses e em todas as consultas eram coletadas CHII e colpocitologia oncológica (CO). Nos retornos, quando necessário, eram realizadas biópsias colpodirigidas e as pacientes com recidiva da NIC submetidas a tratamento. Para fins estatísticos foram avaliadas associações através do Odds ratio, testes de McNemar, Qui-quadrado, exato de Fisher, análise multivariada através da regressão logística e Generalized Estimating Equations. Resultados: No momento da conização diatérmica, a CHII foi positiva em 92% das mulheres. O teste de McNemar mostrou associação significativa entre a detecção do HPV inicial com as detecções em 6 e 12 meses, sendo que nestes momentos apenas 25% das mulheres mantinham HPV detectável. As detecções do vírus ao longo do seguimento não estiveram associadas entre si. A carga viral inicial não se relacionou significativamente com a detecção do vírus ao longo do seguimento. A análise multivariada mostrou associação do tabagismo (OR 2,41; IC 95% 1,01 a 5,75) e da positividade das margens do cone (OR 2,81; IC 1,24 a 6,36) com a detecção do HPV no seguimento. Quanto à ocorrência de persistência ou recidiva da NIC, ter idade maior que 40 anos esteve associado com maior freqüência de doença histológica aos 6 meses (OR 12,36; IC 95% 1,03 a 147,40) e a positividade para o HPV se associou com maior freqüência de persistência ou recidiva em 6 (OR 80,60; IC95% 5,25 a 1235,83) e 12 meses (OR 29,12; IC95% 1,91 a 443,61). A concordância entre CO e CHII foi moderada aos 6 meses (kappa=0,40; IC95% 0,18 a 0,64) e pobre aos 12 meses (kappa=0,28; IC 95% 0,02 a 0,54). Os desempenhos da CO e da CHII em detectar persistência ou recidiva da NIC foram semelhantes, com discreta superioridade da CO em algumas circunstâncias. Conclusão: A detecção do HPV declinou substancialmente após a conização diatérmica, assim permanecendo durante o seguimento, para a maioria das mulheres. A presença de HPV detectável ao longo do seguimento esteve significativamente associada com persistência ou recidiva da NIC, agindo como fator preditivo para doença histológica após o tratamento da NIC 2 ou 3Abstract: Objective: To evaluate the variation in high oncogenic risk human Papillomavirus (HPV) detection by Hybrid Capture II (HCII) and its predictive value in the persistence or recurrence of high-grade cervical intaepithelial neoplasia (CIN) 2 or 3 during the follow-up of women submitted to diathermic conization. Subjects and methods: This was a clinical cohort study. A total of 94 women submitted to diathermic conization, between March 2001 and September 2002 in the Cervical Pathology Unit of Campinas State University (CAISM-UNICAMP) were included. Only women with at least one follow-up visit at 6 or 12 months and with confirmed CIN 2 or 3 in the cone specimens were considered. The follow-up visits were scheduled for 6 and 12 months and in each visit, all women undertook CHII and Pap smear specimens. Colposcopically guided biopsies were taken when necessary and patients with CIN recurrences were treated properly. Statistical analysis included the Odds ratios, McNemar¿s, Qui-squares, Fisher exact tests and multivariate analysis with logistic regression and Generalized Estimating Equations. Results: At the moment when diathermic conization was performed, almost 92% of women were HPV positive. McNemar¿s tests showed significant association between initial HPV detection and HPV positivity at 6 and 12 months, when only 25% of women maintained detectable HPV infection. HPV detection at 6 and 12 months showed not to be related to each other. Initial viral load and HPV detection at 6 and 12 months were not significantly associated. Multivariate analysis showed that smoking (OR 2,41; CI 95% 1,01 a 5,75) and cone margins positivity (OR 2,81; CI 1,24 a 6,36) were associated to HPV detection during follow-up. Regarding CIN persistence or recurrence, age over 40 years was associated with histological disease at 6 months (OR 12,36; CI95% 1,03 a 147,40), but HPV positivity correlated to CIN persistence or recurrence at 6 (OR 80,60; CI95% 5,25 a 1235,83) and 12 months (OR 29,12; CI95% 1,91 a 443,61). The agreement between Pap and CHII results was moderate at 6 months (kappa= 0,40; CI95% 0,18 a 0,64) and poor at 12 months (kappa=0,28; CI 95% 0,02 a 0,54). Performance of Pap and CHII in detecting high-grade CIN persistence or recurrence was quite similar at 6 and 12 months, but Pap performed slightly better at some circumstances. Conclusions: HPV detection reduced substantially after CIN diathermic conization and persisted low at 6 and 12 months measurements for the majority of women. Detectable HPV during follow-up was significantly associated with CIN persistence or recurrence and was a predictive factor for histological disease after CIN 2 or 3 treatmentMestradoTocoginecologiaMestre em Tocoginecologi

ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). MÉTODOS: oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5% (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. RESULTADOS: a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). CONCLUSÕES: nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama.PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5% (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Current physical therapy care of patients undergoing breast reconstruction for breast cancer: a survey of practice in the United Kingdom and Brazil

Background In both the United Kingdom (UK) and Brazil, women undergoing mastectomy should be offered breast reconstruction. Patients may benefit from physical therapy to prevent and treat muscular deficits. However, there are uncertainties regarding which physical therapy program to recommend. Objective The aim was to investigate the clinical practice of physical therapists for patients undergoing breast reconstruction for breast cancer. A secondary aim was to compare physical therapy practice between UK and Brazil. Methods Online survey with physical therapists in both countries. We asked about physical therapists’ clinical practice. Results 181 physical therapists completed the survey, the majority were from Brazil (77%). Respondents reported that only half of women having breast reconstruction were routinely referred to physical therapy postoperatively. Contact with patients varied widely between countries, the mean number of postoperative sessions was 5.7 in the UK and 15.1 in Brazil. The exercise programs were similar for different reconstruction operations. Therapists described a progressive loading structure over time: range of motion (ROM) was restricted to 90° of arm elevation in the first two postoperative weeks; by 2–4 weeks ROM was unrestricted; at 1–3 months muscle strengthening was initiated, and after three months the focus was on sports-specific activities. Conclusion Only half of patients having a breast reconstruction are routinely referred to physical therapy. Patients in Brazil have more intensive follow-up, with up to three times more face-to-face contact with a physical therapist than in the UK. Current practice broadly follows programs for mastectomy care rather than being specific to reconstruction surgery

ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5% (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama319CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP307988/2008-22008/08536-9to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5% (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumor

Prevalência do HPV em mulheres rastreadas para o câncer cervical

OBJECTIVE: To assess the prevalence of high-risk genital human papillomavirus (HPV) infection by age group and risk factors associated. METHODS: Cross-sectional study in a sample of 2,300 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. An epidemiological questionnaire was applied and cervical specimens were obtained for cytology and hybrid capture II test (HCII) for HPV detection. Statistical analysis included Pearson Chi-square and unconditional multiple logistic regression model (forward likelihood ratio). RESULTS: High-risk genital HPV infection prevalence in this sample was 17.8% and age distribution was as follows: 27.1% (OBJETIVO: Analisar a prevalência da infecção genital por papilomavírus humano (HPV) de alto risco por faixa etária e fatores associados. MÉTODOS: Estudo transversal com amostra de 2.300 mulheres (15-65 anos) que buscaram rastreamento para o câncer cervical entre fevereiro de 2002 e março de 2003 em São Paulo e Campinas, estado de São Paulo. Aplicou-se questionário epidemiológico e realizou-se coleta cervical para citologia oncológica e teste de captura híbrida II. As análises estatísticas empregadas foram teste de qui-quadrado de Pearson e análise multivariada pelo método forward likelihood ratio. RESULTADOS: A prevalência total da infecção genital por HPV de alto risco foi de 17,8%, distribuída nas faixas etárias: 27,1%

Expressão da ciclo-oxigenase-2 e do Ki67 em lesões precursoras do cancer do colo uterino

Orientador: Sophie Françoise Mauricette DerchainTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Objetivos: Avaliar a expressão da ciclo-oxigenase-2 (COX-2) em lesões escamosas da cérvice uterina e suas relações com a expressão nuclear do Ki67, a detecção do papilomavírus humano (HPV) e com a persistêncialrecorrência de neoplasia intra epitelial cervical (NIC) após conização diatérmica. Sujeitos e métodos: Este foi um estudo de coorte, com análise intermediária em corte transversal, para o qual foram selecionadas mulheres submetidas à conização diatérmica para o tratamento de anormalidades cervicais, entre fevereiro de 2001 e abril 2004. O estudo é apresentado em dois artigos: o primeiro consiste de análise transversal, incluindo os espécimes cirúrgicos de 164 mulheres submetidas à conização. Foram avaliadas a expressão citoplasmática da COX-2 e a expressão nuclear do Ki67, determinadas por imuno-histoquímica, segundo a gravidade da lesão cervical e a detecção do HPV de alto risco oncogênico, realizada através de Captura de Híbridos 11. No segundo artigo, com análise longitudinal, foram incluídas 104 mulheres com NIC, seguidas por até 36 meses após conização diatérmica, para avaliar possíveis relações entre a expressão da COX-2 e Ki67, comprometimento das margens do cone e d_tecção do HPV (durante o seguimento), com a persistêncialrecorrência da NIC. Resultados: No primeiro artigo pode-se observar que não houve diferença na expressão citoplasmática da COX-2 relacionada à gravidade da lesão cervical, à expressão do Ki67 e à detecção do HPV de alto risco. Houve maior expressão de Ki67 nos espécimes com NIC 3. No segundo artigo, 14 casos de recorrência/persistência da NIC foram detectados durante o seguimento. A expressão citoplasmática da COX-2 e a expressão nuclear do Ki67 foram semelhantes nos casos com ou sem recorrêncialpersistência, e apenas a detecção do HPV de alto risco oncogênico durante o seguimento esteve associada ao maior risco de persistêncialrecorrência da NIC (Razão de risco 7,6; Intervalo de confiança 95% 2,1-28,6). Conclusões: A expressão citoplasmática da COX-2 não esteve relacionada à gravidade da lesão cervical, à expressão de Ki67 ou à infecção pelo HPV. As expressões da COX-2 e do Ki-67 não se relacionaram com a persistência/recorrência da NIC em até 36 meses de seguimentoAbstract: Objectives: To assess the expression of cyclooxygenase-2 (COX-2) in squamous lesions of the uterine cervix and its possible relations to nuclear expression of Ki67, Human papillomavirus (HPV) detection and to the persistence/recurrence of cervical intraepithelial neoplasia (CIN) after diathermic conization. Subjects and methods: This was a prospective study with intermediate cross-sectional analysis, in which women subjected to diathermic conization due to cervical abnormalities were selected between February 2001 and April 2004. The first article is a cross sectional study, including surgical specimens of 164 women subjected to conization. Cytoplasmic expression of COX-2 and nuclear expression of Ki67, ascertained through immunohistochemistry, was evaluated according to cervicallesion grade and high-risk HPV detection through Hybrid Capture 11. In the second article, 104 women ith CIN were included, followed-up for 36 months after diathermic conization, in order to assess possible relation between COX-2 and Ki67 expression, adjusted by the cone margin status and high-risk HPV detection during follow-up with persistentlrecurrent CIN. Results: Cross-sectional analysis of baseline data disclosed that COX-2 protein expression did not differ in relation to grade of cervical lesion, Ki67 expression and high-risk HPV detection. A higher expression of Ki67 was associated exclusively with CIN 3. In the follow-up series, fourteen cases of recurrentlpersistent CIN were detected after diatherrny conization. Persistence/recurrence of CIN were not related to cytoplasmic COX-2 and nuclear Ki67 expression, but had a positive association with high-risk HPV detection during follow-up (Risk Ratio 7.6; 95% confidence interval 2.1-28.6). Conclusion: The cytoplasmic expression of COX 2 did not correlate with cervical lesion grade, nuclear Ki67 expression and high-risk HPV detection. COX-2 and Ki67 expression was not related to persistence/recurrence of CINDoutoradoTocoginecologiaDoutor em Tocoginecologi

Factors Associated With Hpv Persistence After Treatment For High-grade Cervical Intra-epithelial Neoplasia With Large Loop Excision Of The Transformation Zone (lletz).

Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). For this cohort study, a total of 94 women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook Pap smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27 (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were strongly associated with positive HPV during follow-up. HPV persistence following LLETZ was associated with smoking and with the interaction between age and conization margins.31270-

[association Between Sonographic Findings And Histological Diagnosis Of 446 Ovarian Tumors].

The objective was to analyze the correlations between the sonographic features of the ovarian masses and the histological diagnosis. A retrospective study which involved 404 female subjects who had developed 446 ovarian masses was carried out. Patients who had been submitted to surgery due to uni or bilateral ovarian tumors were included and those presenting with an ectopic pregnancy or pelvic inflammatory process were excluded. Data from the patients' medical charts provided the information needed for a detailed study of the following variables: larger diameter, external borders and texture of the sonographic masses. This collected data was correlated to post surgery pathology diagnoses. The magnitude of the associations between pathology diagnoses and sonographic morphologic findings where estimated by the Odds Ratio with its respective confidence intervals of 95%. In their majority, masses were benign tumors (88.1%). Malign masses corresponded to 9.4 % of the total and only 2.5% were borderline. Patients' ages ranged from 13 to 63 years (with an average of 39.1). Regarding the irregular and poorly delimited borders of the masses, the odds ratio for malignancy was of 17.8. After analyses of the sonographic texture the odds ratio of complex texture masses proved to be extremely high (38.6). The anechoic masses with thickened septa had an odds ratio of 35.6, while that of the solid masses was of 15.5. Sonographic analyses of adnexal tumors having more than 7 cm of diameter, irregular and poorly delimited external borders, presenting complex or anechoic textures with thickened septa or solid mass are highly suggestive of malignancy.52176-8