Roberto Euzébio dos Santos

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.

Evaluation of density of Langerhans cells in human cervical intraepithelial neoplasia

Objective. To compare the number of Langerhans cells in areas of CIN 3 and in areas without histopathological alteration adjacent to CIN 3 with those found in histologically normal control cases. Material and methods. Specimens were obtained from 46 normal cervixes from women undergoing hysterectomies due to uterine leiomyomata and 71 from conization specimens for CIN 3. The identification of the Langerhans cells was performed by immunohistochemical analysis, using antibodies to S‐100 protein. The number of intraepithelial Langerhans cells was counted at a 400× magnification under light microscope and a 10 field count was performed in areas of epithelium of the normal cervix (group A), areas of CIN 3 in the conization specimens (group B), and areas of epithelium without histopathologic alteration adjacent to CIN 3 (group C). Results were expressed as number of cells per square millimeter of epithelium. Results. Comparing groups A and B, we observed that the number of Langerhans cells was significantly higher in the latter group; between groups A and C, the number of cells was significantly lower in the second group. The number of Langerhans cells was also compared between groups B and C and it was significantly lower in the latter, independent of smoking habits. Conclusions. We theorize that the increase in the population of Langerhans cells in areas of CIN 3 could be explained by migration of these cells from adjacent areas without histopathologic alterations in order to act in the restraint of the development of neoplasia; cigarette smoking did not influence this migration.

Development of an electronic protocol for uterine cervical cancer

OBJECTIVE Development of an electronic protocol for cancer of the cervix. METHODS We collected data through a literature review and formatted them to build a theoretical base for cancer of the cervix for inclusion in the protocol. The computerized database used the SINPE

Células glandulares atípicas em esfregaços cervicovaginais: significância e aspectos atuais

Atypical glandular cells (AGC) on cervical smears are unusual but important cytologic diagnosis. The incidence of AGC ranges from 0.08% to 0.81 % of all cervical smears tests. The 2001 Bethesda System nomenclature classifi es these glandular lesions as AGC not otherwise specifi ed, AGC favor neoplasia, endocervical adenocarcinoma in situ (AIS) and invasive adenocarcinoma. Of women with AGC smears, a great number will have no histologic abnormalities on further evaluation. However, 17.4% to 62.2% are found to have signifi cant histologic lesions such as cervical intraepithelial neoplasia, AIS, squamous and glandular cancers from sites farther the cervix and endometrium. The risk of signifi cant disease is related to the AGC subclassifi cation that was found. Because of the high likelihood that AGC is associated with signifi cant histological disease, simply repeating the cytological smear is not suffi cient for the management of this condition. This review describes the epidemiology, evaluation and management of patients with these citologic readings.Atypical glandular cells (AGC) on cervical smears are unusual but important cytologic diagnosis. The incidence of AGC ranges from 0.08% to 0.81 % of all cervical smears tests. The 2001 Bethesda System nomenclature classifies these glandular lesions as AGC not otherwise specified, AGC favor neoplasia, endocervical adenocarcinoma in situ (AIS) and invasive adenocarcinoma. Of women with AGC smears, a great number will have no histologic abnormalities on further evaluation. However, 17.4% to 62.2% are found to have significant histologic lesions such as cervical intraepithelial neoplasia, AIS, squamous and glandular cancers from sites farther the cervix and endometrium. The risk of significant disease is related to the AGC subclassification that was found. Because of the high likelihood that AGC is associated with significant histological disease, simply repeating the cytological smear is not sufficient for the management of this condition. This review describes the epidemiology, evaluation and management of patients with these citologic readings.

Avaliação histológica de pólipos endometriais em mulheres após a menopausa e correlação com o risco de malignização

OBJETIVOS: caracterizar histologicamente polipos endometriais em mulheres apos a menopausa e avaliar o risco de lesoes hiperplasicas e neoplasicas neles contidos. METODOS: analise retrospectiva de 82 casos de mulheres portadoras de histopatologia confirmatoria de polipo endometrial, submetidas a polipectomia histeroscopica devido ao diagnostico de espessamento endometrial a ultra-sonografia transvaginal. Todos os prontuarios pertinentes foram revisados para obtencao da historia clinica, antecedentes, dados referentes ao exame histeroscopico e resultado final da histopatologia. RESULTADOS: das 82 mulheres avaliadas, 10,9% faziam uso de algum tipo de terapia hormonal e 28 (34,1%) queixavam-se de sangramento por via vaginal. Polipo solitario foi encontrado em 56 mulheres (68,3%), em 19 casos (23,2%) foram encontrados dois polipos e em 7 casos (3,6%), tres ou mais polipos. A avaliacao histologica definitiva evidenciou polipo benigno em 63 mulheres (76,8%), polipos com hiperplasia em 17 casos (20,8%), sendo dez com hiperplasia simples sem atipias (12,2%) e sete com hiperplasia complexa sem atipias (8,6%). Em dois polipos foi encontrada neoplasia associada (2,4%). Para a analise estatistica foi empregado o teste do c2, corrigido por Yates. Correlacionou-se a histologia dos polipos com a presenca ou nao de sangramento genital (p=0,0056), o numero de polipos encontrados por mulher (p=0,921), e o tempo decorrido apos a menopausa (p=0,720). CONCLUSOES: polipos endometriais sao entidades frequentemente encontradas apos a menopausa, associando-se com baixa frequencia a hiperplasias e carcinomas endometriais e apenas o estudo histologico de todo especime nos permite afastar malignidade.

Prognostic Assessment of Polymorphisms of the MDR‐1 and GSTP1 Genes in Patients with Stage II and III Breast Cancer Submitted to Neoadjuvant Chemotherapy

To the Editor: Breast cancer is currently one of the most prevalent neoplasias in women and accounted for an estimated 192,370 new cases in 2009 in the United States and 40,170 deaths (1). Figures for Brazil show an estimated incidence of 49,240 new cases in 2010 (2). The use of neoadjuvant chemotherapy in patients with locally advanced breast cancer allows treatment response to be determined in vivo, conservative surgery as opposed to the traditional radical approach, and early treatment of micrometastases (3–5). Differing degrees of response to neoadjuvant chemotherapy among similar patient groups in terms of staging suggest the existence of drug-resistance mechanisms induced by intrinsic genetic alterations (6). These mechanisms mainly involve genes which codify proteins that promote the intracellular efflux of drugs from the intracellular medium (MDR-1), inhibiting their action, and genes linked to catalyzing enzymes represented by the Glutathione S-Transferase Pi 1 (GSTP1) which metabolically deactivate the chemotherapy drugs, exerting a synergic action (6–8). Several single nucleotide polymorphisms (SNP) have been described for both the MDR-1 and GSTP1 genes, where these cause functional changes in their proteins and different phenotypes in response to drugs exposure (9–12). The aim of this study was to determine the prognostic value of the most frequent SNPs of the MDR-1 (C3435T) and GSTP1 (A313G––105Ile fi Val) genes in patients with stage II or III breast carcinoma submitted to neoadjuvant chemotherapy, assessing Overall Survival (OS) and Disease-Free Survival (DFS). A longitudinal prospective study was conducted in an initial sample of 52 women with clinically confirmed breast cancer seen at the Department of Obstetrics and Gynecology of Hospital Santa Casa de São Paulo, Brazil. Subjects were recruited between July 2004 and July 2006 and all underwent clinical, laboratory, and radiologic follow-up to December 2009. Of the 52 patients initially recruited, 12 were excluded due to the following factors: one patient was diagnosed with granulomatous mastitis, one patient presented morbid obesity precluding magnetic resonance imaging exam, three patients had metastatic tumors, six patients were diagnosed with invasive lobular carcinoma, and one patient was excluded because their DNA sample presented degradation and they did not attend follow-up in our service. This gave a final group of 40 patients who all met the inclusion criteria. After histopathologic confirmation, the patients were submitted to three cycles of primary chemotherapy, interspersed by 21-day intervals, using the scheme 5-Fluorouracil (500mg ⁄ m), Epirrubicin (75 mg ⁄ m) and Cyclophosphamide (500mg ⁄ m), followed by surgery. Blood samples were collected for subsequent amplification of the genomic regions by PCR. Stages of enzyme digestion by RFLP were then performed to determine the SNPs. Mean disease-free time in our casuistic was 43.8 months, ranging from 4.2 to 64.4 months; mean OS time was 50.3 months, ranging from 19.3 to 64.6 months; a total of 11 deaths were registered during the follow-up period where all mortalities were due to disease progression. Our results showed that patients without lymph node metastases presented longer OS and DFS Address correspondence and reprint requests to: Fábio Francisco Oliveira Rodrigues, MD, MS, R Martiniano de Carvalho, 836 apto 84 bl 3––CEP 01321000, Bela Vista––São Paulo, Brazil, or e-mail: foliveirarodrigues@uol. com.br.

Resultados obtidos em mulheres portadoras de endometriose pélvica avançada e mulheres com ligadura tubária, submetidas a ICSI: análise comparativa

Purpose: comparative analysis of the outcome of women with advanced pelvic endometriosis and women with tubal sterilization submitted to intracytoplasmic sperm injection (ICSI). Methods: ninety-three infertile women, with normal menstrual cycle, without hormonal or surgical treatment during 12 months, body mass index of 20-25, ovaries with no tumors or cysts were included in the present study and divided into two groups: tubal sterilization (TUB), 39 women, and endometriosis (EDT), 54 women with III-EDT and IV-EDT, undergoing ovulatory induction using r-FSH and ICSI. Clinical and laboratorial data were compared. χ 2 , Fisher, Student’s t, and Mann-Whitney tests were employed. Results: lower estradiol levels (2,243.1 vs 1,666.3; p=0.001) and lower number of follicles per patient (16.9 vs 13.9, p=0.001) were noted in EDT group, in spite of more units of r-FSH (1,775.6 vs 1,998.6; p=0.007, for TUB and EDT, respectively). There were no differences in the rates of retrieved oocyte (69 vs 73.5%; p=0.071) as well as in normal fertilization rates (83.7 vs 81.7%; p=0.563, for TUB and EDT, respectively. However, lower number of top quality preembryos were obtained in patients from EDT group (36.5 vs 24.8%, TUB and EDT, respectively; p=0.005). Total pregnancy (41.0 vs 42.6%; p=0.950) and implantation rates (13.9 vs 14.5%; p=0.905) were not different when groups TUB and EDT were compared. Conclusions: ovaries ofPURPOSE: comparative analysis of the outcome of women with advanced pelvic endometriosis and women with tubal sterilization submitted to intracytoplasmic sperm injection (ICSI). METHODS: ninety-three infertile women, with normal menstrual cycle, without hormonal or surgical treatment during 12 months, body mass index of 20-25, ovaries with no tumors or cysts were included in the present study and divided into two groups: tubal sterilization (TUB), 39 women, and endometriosis (EDT), 54 women with III-EDT and IV-EDT, undergoing ovulatory induction using r-FSH and ICSI. Clinical and laboratorial data were compared. c2, Fisher, Students t, and Mann-Whitney tests were employed. RESULTS: lower estradiol levels (2,243.1 vs 1,666.3; p=0.001) and lower number of follicles per patient (16.9 vs 13.9, p=0.001) were noted in EDT group, in spite of more units of r-FSH (1,775.6 vs 1,998.6; p=0.007, for TUB and EDT, respectively). There were no differences in the rates of retrieved oocyte (69 vs 73.5%; p=0.071) as well as in normal fertilization rates (83.7 vs 81.7%; p=0.563, for TUB and EDT, respectively. However, lower number of top quality preembryos were obtained in patients from EDT group (36.5 vs 24.8%, TUB and EDT, respectively; p=0.005). Total pregnancy (41.0 vs 42.6%; p=0.950) and implantation rates (13.9 vs 14.5%; p=0.905) were not different when groups TUB and EDT were compared. CONCLUSIONS: ovaries of women from EDT group seem to be less responsive to ovulatory induction with r-FSH. EDT seems to impair the mean number of follicles and top quality preembryos with no impairment of retrieved oocyte and fertilization rates. However, once obtained, preembryos from EDT patients are able to exhibit similar implantation potential and pregnancy when compared with patients from TUB group.

Chemotherapy and Mechanisms of Resistance in Breast Cancer

1.1 Adjuvant In the mid 1950s, we started to have a much better understanding of the biological mechanisms of establishment of metastases and the role of regional lymph nodes as an effective barrier to tumor spread, because malignant cells have been observed in the bloodstream (Fisher, Turnbull, 1955). Early studies with adjuvant chemotherapy after surgery in solid tumors (breast adenocarcinoma implanted in mice) began in 1957 (Shapiro, Fugman, 1957). Based on these findings, Bernard Fisher and colleagues began in 1958, the first collaborative study with the objective of evaluating the response to systemic administration of perioperative chemotherapy in patients with operable breast cancer (Fisher et al, 1958). Good results were obtained in relation to disease-free interval and overall survival in premenopausal women (Fisher et al, 1968). Similar results were also observed by other authors, with the use of multidrug therapy (cyclophosphamide, methotrexate and fluorouracil (CMF) with or without prednisone) in advanced breast cancer (BC)(Canellos et al, 1974 and 1976, Bonadonna et al, 1976). Therefore, the addition of adjuvant polychemotherapy in BC showed gain by controlling survival of micrometastases in patients with lymph nodes affected by cancer or not (Fisher et al, 1975; Bonadonna et al, 1976; Early Breast Cancer Trialists Collaborative Group (EBCTCG ), 1988; Bonadonna, Valagussa, 1983,1985,1987, Henderson, 1987, Fisher et al, 1989; Bonadonna et al, 1995; Mansour et al, 1998, Carlson et al, 2000 and NIH 2000).

Citorredução de intervalo no carcinoma avançado do ovário: experiência da Santa Casa de São Paulo

OBJECTIVE To analyze the interval cytoreduction in patients with advanced ovarian cancer. METHODS A prospective study was carried out with 25 patients with advanced ovarian cancer (stages IIIC or IV) who underwent interval cytoreduction. Nonresectability criteria were based on the ones from Gustave-Rousy Institute. After induction chemotherapy and rapprochement we evaluated the rates of optimal surgery and the morbidity and mortality of the procedure in addition to the overall survival at two years. RESULTS optimal cytoreduction was possible in 17 patients (68%) with morbidity and mortality from 8% to 4%. The overall survival at two years was 68%. CONCLUSION The interval cytoreduction is an alternative therapy in advanced ovarian cancer, allowing optimal cytoreduction opportunity to patients suffering from unresectable disease, with acceptable morbidity and mortality.