Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

Cancer risk-reducing surgery: Brazilian Society of Surgical Oncology Guideline Part 2 (Gastrointestinal and thyroid).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Eleven questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reducing colectomy, gastrectomy, and thyroidectomy, a major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO and it should serve as an important reference for the management of families with cancer predisposition.

Helicobacter pylori and other factors in recurrent aphthous stomatitis: A cross-sectional study.

OBJECTIVES: To evaluate the role of Helicobacter pylori and other risk factors in recurrent aphthous stomatitis (RAS). METHODS: Patients with functional dyspepsia responded to questionnaires regarding demographic and clinical data, anxiety and depression, and a specific RAS questionnaire. They underwent upper digestive endoscopy and H. pylori evaluation. RESULTS: 476 patients were included and of the 372 evaluated for H. pylori, 65.6% were H. pylori-positive. RAS was reported by 32.6% (155/476). In the bivariate analysis of the 372 patients evaluated for gastric H. pylori status, positive subjects had a lower RAS prevalence (29.9%; 73/244) than H. pylori-negative (41.4%; 53/128) (p = .026). Smoking (p = .005) and older age (p = .034) were also associated with a lower prevalence, while female gender (p = .032) and lower income (p = .046) presented higher RAS prevalence. In the multivariate analysis, H. pylori infection (p = .017), smoking (p = .001), and older age (p = .013) were protective factors, while lower income (p = .030) and anxiety (p = .042) were risk factors. In the multivariate analysis of all patients, female gender, lower income, and more schooling years were risk factors. CONCLUSIONS: An unexpected lower prevalence of RAS was found in H. pylori-positive patients. Smoking, sex, age, income, education, and anxiety were associated with RAS.

Potential roles of Helicobacter pylori treatment, body mass index and waist circumference in the causation of erosive esophagitis: a randomized clinical trial (HEROES-GERD).

BACKGROUND: In recent decades, the prevalence of gastroesophageal reflux disease (GERD) and obesity has been increasing while Helicobacter pylori infection has been decreasing. OBJECTIVE: To evaluate if H. pylori treatment, excess body weight and other anthropometric measurements are associated with incident erosive esophagitis, as a secondary objective of a trial which tested the efficacy of treatment of H. pylori on the symptoms of functional dyspepsia. SUBJECTS/METHODS: Upper gastrointestinal endoscopy and anthropometric assessments were performed, at baseline and after 12 months, in H. pylori positive patients with functional dyspepsia who had no baseline reflux symptoms or esophagitis. Patients were randomly assigned to receive omeprazole, amoxicillin, and clarithromycin (antibiotic group; n = 201) or omeprazole plus placebo (control group; n = 203). The primary outcome was the incidence of esophagitis 12 months after randomization, according to treatment groups, and the association of BMI and other anthropometric measurements. RESULTS: Four hundred and four patients were included (mean age, 46.1 years; 78.7% women). The 12-month follow-up endoscopic esophagitis rates for the antibiotic and control groups were 10.9% (22/201) and 9.4% (19/203), respectively (p = 0.60). The number needed to harm was 67. Baseline anthropometric measurements were performed in 94% (380/404) of patients. The 12-month follow-up esophagitis rates for overweight and normal body weight patients were 13.6% (29/213) and 6.0% (10/167), respectively (p = 0.015); rates for patients with and without increased baseline waist circumference were 15.4% (24/156) and 6.7% (15/224), respectively (p = 0.006). Following logistic regression, only the combination of increased baseline body mass index and waist, but not H. pylori treatment, was independently associated with new-onset esophagitis (OR 2.88; 95% CI: 1.28-6.45). CONCLUSIONS: Excess body weight and concomitant increased waist circumference, but not H. pylori treatment, predicts new-onset esophagitis.

Guidelines of the Brazilian Society of Oncologic Surgery for pelvic exenteration in the treatment of cervical cancer.

BACKGROUND AND OBJECTIVES: The primary treatment for locally advanced cases of cervical cancer is chemoradiation followed by high-dose brachytherapy. When this treatment fails, pelvic exenteration (PE) is an option in some cases. This study aimed to develop recommendations for the best management of patients with cervical cancer undergoing salvage PE. METHODS: A questionnaire was administered to all members of the Brazilian Society of Surgical Oncology. Of them, 68 surgeons participated in the study and were divided into 10 working groups. A literature review of studies retrieved from the National Library of Medicine database was carried out on topics chosen by the participants. These topics were indications for curative and palliative PE, preoperative and intraoperative evaluation of tumor resectability, access routes and surgical techniques, PE classification, urinary, vaginal, intestinal, and pelvic floor reconstructions, and postoperative follow-up. To define the level of evidence and strength of each recommendation, an adapted version of the Infectious Diseases Society of America Health Service rating system was used. RESULTS: Most conducts and management strategies reviewed were strongly recommended by the participants. CONCLUSIONS: Guidelines outlining strategies for PE in the treatment of persistent or relapsed cervical cancer were developed and are based on the best evidence available in the literature.

Immunohistochemical and clinicopathologic features of estrogen receptor-negative, progesterone receptor-positive, HER-2 negative breast carcinomas.

OBJECTIVE: Currently, there is an ongoing debate whether progesterone receptor positive and estrogen receptor negative breast carcinomas represent a true distinct subtype of tumor or a mere immunohistochemical artifact. In this study, we conducted an immunohistochemistry panel with the antibodies TFF1, EGFR, and CK5 to reclassify this phenotype in a luminal or basal-like subtype. METHODS: Tumors estrogen receptor -/progesterone receptor +, Her-2 - from a large population of breast cancer patients were selected to be studied. Immunohistochemistry with the antibodies TFF1, EGFR, and CK5 was performed. Tumors showing positivity for TFF1, regardless of EGFR and CK5 results, were classified as luminal-like carcinomas. Those lesions that were negative for TFF1, but were positive for EGFR and/or CK5, were classified as basal-like triple-negative carcinomas. When the three markers were negative, tumors were classified as undetermined. Clinical pathologic characteristics of patients and tumor recurrence were evaluated. RESULTS: Out of 1188 breast carcinomas investigated, 30 cases (2.5%) presented the estrogen receptor -/progesterone receptor +/HER2- phenotype. Of them, 27 tumors (90%) were classified as basal-like triple-negative carcinomas, one as luminal-like (3.3%), and two as undetermined tumors (6.7%). The mean follow-up for the study group was 27.7 (2.7 to 50) months. Out of the 26 patients, 6 had cancer recurrence: 2 local and 4 systemic recurrences. The average time for recurrence was 17 (8 to 38) months. CONCLUSION: Estrogen receptor -/progesterone receptor +/tumors exhibit aggressive behavior, similar to triple-negative tumors. An appropriate categorization of these tumors should be made to improve their therapeutic management.

Prognostic Factors of Long-term Survival Following Radical Resection for Ampullary Carcinoma.

BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.

ASSOCIATION OF DUODENAL EOSINOPHILIC INFILTRATE WITH HELICOBACTER PYLORI INFECTION, BUT NOT WITH FUNCTIONAL DYSPEPSIA.

BACKGROUND: The role of Helicobacter pylori infection on eosinophilic infiltration in duodenal mucosa is poorly studied. An increase in the number of eosinophils in duodenum has been associated with functional dyspepsia. OBJECTIVE: To evaluate the influence of H. pylori infection on duodenal eosinophil count and the role of eosinophilic infiltrate of duodenum in functional dyspepsia. METHODS: Positive and negative H. pylori individuals were included. Both functional dyspeptic patients according to Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were enrolled. They were submitted to upper endoscopy and H. pylori infection was verified by gastric histopathology and urease test. Eosinophils in the duodenal mucosa were counted in five high-power fields, randomly selected on slides of endoscopic biopsies. RESULTS: Thirty-nine H. pylori positive (mean age 40.5 and 69.2% women) and 24 negative patients (mean age 37.3 and 75% women) were included. The influence of the infection was observed in the duodenal eosinophil count, which was higher in infected individuals: median 13.2 vs 8.1 in non-infected individuals (P=0.005). When we analyzed patients according to symptoms, cases - mean age 39.6; 71.4% women - and controls - mean age 38.7; 71.4% women - had similar duodenal eosinophil count: median 11.9 and 12.6 respectively (P=0.19). CONCLUSIONS: We did not demonstrate association of duodenal eosinophil count with functional dyspepsia but found association with H. pylori infection.

Assessment of HER-2 status in invasive breast cancer in Brazil.

OBJECTIVE: To characterize the frequency of HER-2-positive breast cancer in Brazil. METHOD: In this prospective observational study, we first ascertained the HER-2 status of invasive breast cancer specimens by automated immunohistochemistry (IHC). For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH). RESULTS: From February, 2011 to December, 2012, 1,495 breast specimens were registered, and 1,310 samples collected at 24 centers were analyzed. Median patient age was 54 years, and the majority of samples were obtained from segmental (46.9%) or radical mastectomy (34.4%). The predominant histological type was invasive breast carcinoma of no special type (85%), 64.3% had tubule formation (grade 3), and estrogen/progesterone receptors (ER/PR) were positive in 77.4/67.8% of the specimens analyzed, respectively. Using IHC, we found a negative HER-2 status (0 or 1+) in 72.2% of specimens, and 3+ in 18.5%; the 9.3% scored as 2+ were further analyzed by ISH, of which 15.7% were positive (thus, 20.0% of samples were HER-2- -positive by either method). We found no association between HER-2 scores and menopausal status or histological type. Tumors classified as 3+ came from younger patients, and had higher histological grade and less frequent expression of ER/PR. In the North region of Brazil, 34.7% of samples were 3+, with lower frequencies in the other four regions of the country. CONCLUSION: Our findings provide estimates for the frequency of HER-2 positivity in Brazil and raise the hypothesis that biological differences may underlie the different distribution of breast-cancer phenotypes among different Brazilian regions.

The effects of passive tobacco smoking on the microcirculation of the abdominal wall in rats.

PURPOSE:: To analysis the effects of passive smoking on the microstructure of tissues of the abdominal wall regarding microcirculation, using histopathological study of the tobacco exposed rats. METHODS:: Twenty four male Wistar rats were divided in Control Group (CG = 8 animals) and Exposition Groups (EG = 16 animals). EG was exposed to cigarette smoke 4x/day for 120 days, while CG was preserved from exposure. Food, water and housing were similar for both groups. After 120 days, urine samples were collected before necropsy to analyze cotinine levels (ng/mL) in urine and blinded histopathological analysis of the abdominal wall performed to count arteries and veins in dermal and muscular fascia layer. RESULTS:: No difference in weight was observed between both groups (P>0.05). Cotinine concentration was significantly higher in EG (P<0.05). In dermal layer, the average of vessels per animal was 8.72 (IC95%: 8.31-9.13) for CG and 11,23 (IC95%: 10.09-12.38) for EG. In muscular fascia layer the average of vessels per animal was 17.97 (IC95%: 15.79-20.15) for CG, whereas the average for EG was of 14,85 (IC95%: 12.71-17.01) (P<0.05). CONCLUSION:: Exposition to passive smoking may cause increase in the number of vessels in dermal layer, with the opposite effects at the muscular fascia layer.

Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis.

BACKGROUND: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. METHODS: A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. RESULTS: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. CONCLUSION: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool.

Associação de infiltrado eosinofílico duodenal com infecção por Helicobacter pylori, mas não com dispepsia funcional / Association of duodenal eosinophilic infiltrate with helicobacter pylori infection, but not with functional dyspepsia

ABSTRACT BACKGROUND: The role of Helicobacter pylori infection on eosinophilic infiltration in duodenal mucosa is poorly studied. An increase in the number of eosinophils in duodenum has been associated with functional dyspepsia. OBJECTIVE: To evaluate the influence of H. pylori infection on duodenal eosinophil count and the role of eosinophilic infiltrate of duodenum in functional dyspepsia. METHODS: Positive and negative H. pylori individuals were included. Both functional dyspeptic patients according to Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were enrolled. They were submitted to upper endoscopy and H. pylori infection was verified by gastric histopathology and urease test. Eosinophils in the duodenal mucosa were counted in five high-power fields, randomly selected on slides of endoscopic biopsies. RESULTS: Thirty-nine H. pylori positive (mean age 40.5 and 69.2% women) and 24 negative patients (mean age 37.3 and 75% women) were included. The influence of the infection was observed in the duodenal eosinophil count, which was higher in infected individuals: median 13.2 vs 8.1 in non-infected individuals (P=0.005). When we analyzed patients according to symptoms, cases - mean age 39.6; 71.4% women - and controls - mean age 38.7; 71.4% women - had similar duodenal eosinophil count: median 11.9 and 12.6 respectively (P=0.19). CONCLUSIONS: We did not demonstrate association of duodenal eosinophil count with functional dyspepsia but found association with H. pylori infection.

RESUMO CONTEXTO: O papel de infecção por Helicobacter pylori no infiltrado eosinofílico duodenal ainda é pouco compreendido. Um aumento no número de eosinófilos duodenais tem sido associado a dispepsia funcional. OBJETIVO: Avaliar a influência do H. pylori na contagem de eosinófilos duodenais e o papel do infiltrado eosinofílico duodenal na dispepsia funcional. MÉTODOS: Indivíduos H. pylori positivo e negativo foram incluídos. Ambos os grupos, compreendendo dispépticos funcionais pelos critérios de Roma III (casos) e indivíduos sem sintomas gastrointestinais (controles), foram submetidos à endoscopia digestiva alta para pesquisa de H. pylori, efetuada por histopatologia e teste de urease. Eosinófilos na mucosa duodenal foram contabilizados em cinco campos de maior aumento, selecionados randomicamente nas lâminas de biópsia endoscópicas. RESULTADOS: Trinta e nove indivíduos H. pylori positivo (média de idade 40,5 e 69,2% mulheres) e 24 H. pylori negativos (média de idade 37,3 e 75% mulheres) foram incluídos. A influência da infecção por H. pylori foi observada na contagem de eosinófilos, que foi maior nos positivos: mediana 13,2 vs 8,1 (P=0,005). Quando analisados pacientes de acordo com sintomas, os casos (média de idade 39,6 e 71,4% mulheres) e controles (média de idade 38,7 e 71,4% mulheres), apresentaram semelhante contagem de eosinófilos duodenais: mediana 11,9 e 12,6, respectivamente (P=0,19). CONCLUSÃO: Não demonstramos associação da contagem de eosinófilos duodenais com dispepsia duodenal, mas encontramos associação com infecção por H. pylori.

Comparison between preoperative and intraoperative injection of (99m)Tc Dextran-500 for sentinel lymph node localization in breast cancer.

A retrospective study was conducted from a review of the medical records of patients with early-stage, invasive breast cancer who underwent surgical treatment and sentinel node biopsy with a radiotracer from January 2008 to August 2012 at a single institution (221 patients included). The patients were grouped according to the time of (99m)Tc Dextran-500 injection, which was preoperatively (with lymphoscintigraphy) (81 patients) or intraoperatively (140 patients). The purpose of the report is to compare the results of sentinel node biopsy of early-stage breast cancer patients who were subjected to intraoperative (99m)Tc Dextran-500 injections with the patients who received preoperative injections. The following parameters were analyzed: clinical tumor staging, histological and pathological results, size and number of tumor foci, peritumoral vascular invasion, number of lymph nodes removed, size of lymph node metastasis and hormone receptor expression.There were no differences in sentinel lymph node localization whether (99m)Tc Dextran-500 was injected preoperatively or intraoperatively.

Expression of cancer stem cell markers in basal and penta-negative breast carcinomas--a study of a series of triple-negative tumors.

PURPOSE: Breast cancer is a heterogeneous disease. Immunohistochemistry has given rise to triple-negative carcinoma (TNC). Concomitantly, biological origins of neoplasia and its heterogeneity has been strongly debated in cancer stem cells (CSC) theme. This study investigates the prevalence of basal (BCC) and penta-negative carcinomas (5NC) in TNC and establishes associations with CSC (CD44CD24). MATERIALS AND METHODS: 94 TNC were tested for CK5/6, HER1, CD44 and CD24, evaluated by a simple immunohistochemistry score and correlated with clinicopathological and survival data. RESULTS: BCC had higher tumor grades than 5NC (p=0.004). CD44 negativity (p=0.007) and CD44(-)CD24(+) phenotype (p=0.013) were associated with less vascular invasion amongst TNC. CD44 expression was associated with BCC (p=0.007). CD44(-)CD24(-/low) phenotype was associated with 5NC. None of the variables were associated with clinical outcome. CONCLUSION: BCC and 5NC are closely related tumor subtypes. CD44(-)CD24(-/low) phenotype was associated with 5NC and CD44(-)CD24(+) phenotype was associated with vascular invasion. These results require histogenetic confirmation in larger studies.

CLAUDINS 1, 3, 4, 7 AND 10-YEAR SURVIVAL IN TRIPLE-NEGATIVE BREAST TUMORS / Claudinas 1, 3, 4, 7 e sobrevida de 10 anos em tumores de mama triplo-negativos

Purpose: Breast cancer is a major cause of morbidity and mortality and is known to be a heterogeneous disease. The clinical and molecular characterization of its subtypes is critical to guide its prognosis and treatment. The study of the expression of Claudins (CLDN) might help in the characterization of these tumors. This study investigated the association of expression of CLDN-1, CLDN-3, CLDN-4 and CLDN-7 with 10-year survival in a series of triple-negative breast cancers. Methods: Eighty triple negative tumors were analyzed by automated immunohistochemistry for CLDN-1, CLDN-3, CLDN-4 and CLDN-7. The immunohistochemical expression was assessed by the H-Score (intensity multiplied by the percentage of staining on membrane). The associations between the expression of CLDN and 10-year survival were evaluated by Kaplan-Meier curves and Cox regressions. Results: Positive expression (H-score ≥50) of CLDN-1, CLDN-3, CLDN-4 and CLDN-7 were observed in 41.3, 77.5, 67.5 and 18.8% of the cohort, respectively. Patients with positive CLDN-1 expression had a significant lower survival than their counterparts [HR=2.37 (95%CI 1.19­4.72)]. Further, CLDN-3 was inversely associated with overall survival. Patients with positive expression of CLDN-1 and negative expression of CLDN-3 had a HR 10.4 (95%CI 3.40­31.8) higher than patients with negative expression of CLDN-1 and positive expression of CLDN-3. Neither CLDN-4 nor CLDN-7 expression was associated with 10-year survival. Conclusions: Differential expression of CLDN can help in clinicopathological characterization of triple-negative tumors. Moreover, CLDN-1 and CLDN-3 appear to be important prognostic factors for these tumors.

Objetivo: O câncer de mama é uma das principais causas de morbidade e mortalidade, conhecido por ser uma doença heterogênea. A caracterização clínica e molecular de seus subtipos é fundamental para orientar seu prognóstico e tratamento. O estudo da expressão de claudinas (CLDN) pode auxiliar na caracterização desses tumores. Este estudo investigou a associação da expressão de CLDN-1, CLDN-3, CLDN-4 e CLDN-7 com 10 anos de sobrevida em uma série de cânceres de mama triplo-negativos. Métodos: Oitenta tumores triplo-negativos foram analisados por imuno-histoquímica automatizada para CLDN-1, CLDN-3, CLDN-4 e CLDN-7. A expressão imuno-histoquímica foi avaliada pelo escore H (intensidade multiplicada pela porcentagem de coloração na membrana). As associações entre a expressão de CLDN e a sobrevida em 10 anos foram avaliadas pelas curvas de Kaplan-Meier e regressões de Cox. Resultados: Foi observada expressão positiva (escore H ≥ 50) de CLDN-1, CLDN-3, CLDN-4 e CLDN-7 em 41,3, 77,5, 67,5 e 18,8% da coorte, respectivamente. Pacientes com expressão positiva de CLDN-1 tiveram uma sobrevida significativamente menor do que suas contrapartes [HR = 2,37 (IC 95% 1,19-4,72)]. Além disso, o CLDN-3 foi inversamente associado à sobrevida global. Pacientes com expressão positiva de CLDN-1 e expressão negativa de CLDN-3 tiveram uma FC 10,4 (IC 95% 3,40­31,8) vezes maior do que pacientes com expressão negativa de CLDN-1 e expressão positiva de CLDN-3. Nem a expressão de CLDN-4 nem de CLDN-7 foi associada a uma sobrevida de 10 anos. Conclusões: A expressão diferencial de CLDN pode ajudar na caracterização clinico-patológica de tumores triplo-negativos. Além disso, CLDN-1 e CLDN-3 parecem ser importantes fatores prognósticos para esses tumores.

Assessment of HER-2 status in invasive breast cancer in Brazil / Avaliação de HER-2 no câncer de mama invasivo no Brasil

Summary Objective: To characterize the frequency of HER-2-positive breast cancer in Brazil. Method: In this prospective observational study, we first ascertained the HER-2 status of invasive breast cancer specimens by automated immunohistochemistry (IHC). For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH). Results: From February, 2011 to December, 2012, 1,495 breast specimens were registered, and 1,310 samples collected at 24 centers were analyzed. Median patient age was 54 years, and the majority of samples were obtained from segmental (46.9%) or radical mastectomy (34.4%). The predominant histological type was invasive breast carcinoma of no special type (85%), 64.3% had tubule formation (grade 3), and estrogen/progesterone receptors (ER/PR) were positive in 77.4/67.8% of the specimens analyzed, respectively. Using IHC, we found a negative HER-2 status (0 or 1+) in 72.2% of specimens, and 3+ in 18.5%; the 9.3% scored as 2+ were further analyzed by ISH, of which 15.7% were positive (thus, 20.0% of samples were HER-2- -positive by either method). We found no association between HER-2 scores and menopausal status or histological type. Tumors classified as 3+ came from younger patients, and had higher histological grade and less frequent expression of ER/PR. In the North region of Brazil, 34.7% of samples were 3+, with lower frequencies in the other four regions of the country. Conclusion: Our findings provide estimates for the frequency of HER-2 positivity in Brazil and raise the hypothesis that biological differences may underlie the different distribution of breast-cancer phenotypes among different Brazilian regions.

Resumo Objetivo: Estimar a frequência de câncer de mama positivo para HER-2 no Brasil. Método: Neste estudo observacional e prospectivo, verificamos o escore de HER-2 de espécimes de câncer de mama invasivo por imuno-histoquímica automatizada (IHQ). Para amostras classificadas como 2+ por IHQ, fizemos hibridização in situ (HIS). Resultados: De fevereiro de 2011 a dezembro de 2012, 1.495 espécimes de mama foram registrados, e 1.310 amostras coletadas por 24 centros foram analisadas. A idade mediana das pacientes foi 54 anos, e a maioria das amostras foram obtidas a partir de mastectomia segmentar (46,9%) ou radical (34,4%). O tipo histológico predominante foi o carcinoma invasivo da mama, sem tipo especial (85%); 64,3% tinham formação de túbulos (grau 3); e os receptores de estrógeno (RE)/progesterona (RP) foram positivos em 77,4%/67,8% das amostras analisadas. Por IHQ, encontramos HER-2 negativo (0 ou 1+) em 72,2% das amostras, e 3+ em 18,5%; os 9,3% de casos classificados como 2+ foram analisados por HIS, e 15,7% deles foram positivos (assim, 20,0% das amostras foram positivas para HER-2 por qualquer método). Não encontramos associação entre escores de HER-2 e estado menopausal ou tipo histológico. Tumores classificados como 3+ vieram de pacientes mais jovens, tinham maior grau histológico e foi menos frequente a expressão de RE/RP. Na região Norte do Brasil, 34,7% das amostras foram 3+, com frequências mais baixas nas outras quatro regiões do país. Conclusão: Nossos resultados permitem estimar a frequência de positividade do HER-2 no Brasil, gerando a hipótese de que pode haver diferenças biológicas subjacentes à distribuição dos fenótipos de câncer de mama entre as diferentes regiões brasileiras.

The effects of passive tobacco smoking on the microcirculation of the abdominal wall in rats

ABSTRACT PURPOSE: To analysis the effects of passive smoking on the microstructure of tissues of the abdominal wall regarding microcirculation, using histopathological study of the tobacco exposed rats. METHODS: Twenty four male Wistar rats were divided in Control Group (CG = 8 animals) and Exposition Groups (EG = 16 animals). EG was exposed to cigarette smoke 4x/day for 120 days, while CG was preserved from exposure. Food, water and housing were similar for both groups. After 120 days, urine samples were collected before necropsy to analyze cotinine levels (ng/mL) in urine and blinded histopathological analysis of the abdominal wall performed to count arteries and veins in dermal and muscular fascia layer. RESULTS: No difference in weight was observed between both groups (P>0.05). Cotinine concentration was significantly higher in EG (P<0.05). In dermal layer, the average of vessels per animal was 8.72 (IC95%: 8.31-9.13) for CG and 11,23 (IC95%: 10.09-12.38) for EG. In muscular fascia layer the average of vessels per animal was 17.97 (IC95%: 15.79-20.15) for CG, whereas the average for EG was of 14,85 (IC95%: 12.71-17.01) (P<0.05). CONCLUSION: Exposition to passive smoking may cause increase in the number of vessels in dermal layer, with the opposite effects at the muscular fascia layer.

Helicobacter pylori eradication in functional dyspepsia: HEROES trial.

BACKGROUND: Eradication of Helicobacter pylori in patients with functional dyspepsia continues to be a matter of debate. We studied eradication effects on symptoms and quality of life of primary care patients. METHODS: Helicobacter pylori -positive adult patients with functional dyspepsia meeting the Rome III International Consensus criteria were randomly assigned to receive omeprazole, amoxicillin trihydrate, and clarithromycin, or omeprazole plus placebo for 10 days. Endoscopy and H pylori tests were performed at screening and at 12 months. Outcome measures were at least 50% symptomatic improvement at 12 months using a validated disease-specific questionnaire (primary end point), patient global assessment of symptoms, and quality of life. RESULTS: We randomly assigned 404 patients (78.7% were women; mean age, 46.1 years); 201 were assigned to be treated with antibiotics (antibiotics group) and 203 to a control group. A total of 389 patients (96.3%) completed the study. The proportion of patients who achieved the primary outcome was 49.0% (94 of 192) in the antibiotics group and 36.5% (72 of 197) in the control group (P = .01; number needed to treat, 8). In the patient global assessment of symptoms, 78.1% in the antibiotics group (157 of 201) answered that they were better symptomatically, and 67.5% in the control group (137 of 203) said that they were better (P = .02). The antibiotics group had a significantly larger increase in their mean (SD) Medical Outcomes Study 36-Item Short Form Health Survey physical component summary scores than the control group did (4.15 [8.5] vs 2.2 [8.1]; P = .02). CONCLUSION: Helicobacter pylori eradication provided significant benefits to primary care patients with functional dyspepsia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00404534.

Myofibroblastoma arising in mammary hamartoma: a case report.

Myofibroblastoma (MFB) is a rare mesenchymal tumor arising in breast's soft tissue with a great variety of microscopic features that can be mistaken with a wide variety of biphasic lesions. The authors report a rare case of myofibroblastoma of the breast arising in a mammary hamartoma (MH), present a review of the clinicopathological features of these lesions, and make some diagnostic considerations. The tumour consisted of a well-circumscribed nodule. MFB component comprised about fifty percent of the lesion and was made up of bipolar spindle cells arranged in fascicular clusters separated by bands of hyalinized collagen. There were fat cells and several residual hamartoma glands intermingled and distorted in MFB area. MFB component was positive for Desmin, CD34, bcl-2, and Calponin. To the best of our knowledge, MFB has not been reported in MH, neither has any of the reports described mammary glands joined within MFB.

Analysis of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast carcinoma.

Breast cancer is the most common neoplasia as well as the main cause of cancer-related death among women, experiencing a 0.5% increase in incidence per year. The disease results from a series of mutations in the DNA development and repair genes. Approximately 50% of human carcinomas present mutations in the TP53 gene. Polymorphisms of TP53 include codon 72 containing either arginine (CGC) or proline (CCC). Such polymorphisms may be involved in the susceptibility and predisposition to cancer, presenting a widely variable ethnic and geographic distribution. The arginine homozygous genotype seems to be a significant risk factor for breast cancer. The purpose of this study was to determine the frequency of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast cancer from southern Brazil, where this type of cancer has a high incidence, as well as its association with breast carcinoma and clinicopathological characteristics. Seventy-six patients suffering from invasive ductal breast cancer and 80 controls were analyzed, and samples were evaluated by PCR followed by restriction enzyme digestion. No statistical differences in terms of the genotype frequency (P=0.707) or the arginine and proline allele frequencies (P=0.469) involving codon 72 were found in patients compared to controls. Thus, statistical analysis did not suggest any association between the R72P polymorphism of the TP53 gene and invasive ductal carcinoma in the population studied. Additionally, no significant association with the clinicopathological characteristics presented by the breast carcinoma patients was found.