Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections.

BACKGROUND: Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data. METHODS: Histological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations. RESULTS: Immunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén's intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography. CONCLUSIONS: Confronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.

Th1 immune response to H. pylori infection varies according to the age of the patients and influences the gastric inflammatory patterns.

To compare children and adults in respect to the effect of H. pylori infection on the gastric concentrations of cytokines linked to innate and Th1 immune response, as well as to investigate the changes in the gastric concentrations of the studied cytokines according to the age. We studied 245 children (142 H. pylori-negative and 103 H. pylori-positive) and 140 adults (40 H. pylori-negative and 100 H. pylori-positive). The gastric concentrations of cytokines representative of the innate and Th1 response were higher in the H. pylori-positive than in the -negative children and adults. The gastric concentrations of IL-1α and TNF-α were significantly higher, while those of IL-2, IL-12p70 and IFN-γ were lower in the infected children than in the infected adults. In the infected children, the gastric concentration of IL-1α, IL-2, IL-12p70 and IFN-γ increased, whereas in adults, the gastric concentrations of IFN-γ and IL-12p70 decreased with the aging. Increased gastric concentration of Th1 associated cytokines correlated with increased degree of gastritis that is the background lesion for the development of the H. pylori associated severe diseases. Concluding, Th1 response to H. pylori infection varies according to the age and seems to have determinant implication in the H. pylori infection outcomes.

STAG2 expression in oral cancer and potentially malignant lesions.

Oral cancer is a world health problem, and one of the highest incidence rates of oral cancer worldwide occurs in Brazil. STAG2 is part of the cohesin complex which is responsible for sister chromatid cohesion. STAG2 loss of expression was reported in a range of tumors, and STAG2 loss was found to cause chromosomal instability and aneuploidy in cancer cells. On the basis of these findings, we investigated STAG2 expression in oral cancer and potentially malignant lesions. We investigated STAG2 immunoexpression in oral cancer, lip cancer, oral leukoplakia, and actinic cheilitis, including complete clinical information. Normal oral mucosa samples were included as normal controls. STAG2 protein was highly expressed in all samples. We further tested STAG2 expression in gastric adenocarcinomas and glioblastomas, as these tumor types were previously shown to lose STAG2 expression. We found homogenous expression of STAG2 by these tumor cells. Our results suggest that STAG2 loss of expression is not a common event in oral carcinogenesis.

Colorectal carcinoma in different age groups : a histopathological analysis.

PURPOSE: Although colorectal cancer is typical in the older population, tumor onset before age 40 is not infrequent. However, the behavior, characteristics, and prognosis of this disease in young patients are unclear when compared to the older population. It is believed that young patients have a poor prognosis. We hypothesized that young patients have a poor prognosis because they have advanced-stage cancer with more aggressive pathologic features. METHODS: Using a university hospital database, we analyzed the histopathological features of three groups of patients with a diagnosis of colorectal cancer: young age group (patients 40 years and younger), intermediate age group (patients 41-80 years old), and old age group (patients 81 years and older). RESULTS: A total of 653 cases of colorectal cancer were analyzed. The young age group comprised 48 patients (7.4%), the intermediate age group comprised 538 patients (82.4%) and the old age group consisted of 67 patients (10.3%).The gender distribution was similar between the groups. The mean age of the young, intermediate, and old age groups were 34.5 (±5.0), 61.7 (±11.1) and 85.1 (±4.6) years old, respectively. The pathological features analyzed such as lymph node involvement, tumor histological classification and grade, venous, neural and lymphatic invasion, T and N classification of the TNM System, and Astler-Coller classification were similar between the age groups. CONCLUSIONS: The colorectal histopathological features in young patients are similar to older patients. More aggressive characteristics or more advanced stage are not seen in younger patients.

Assessment of vascular invasion in gastric cancer: a comparative study.

AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematoxylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens from a consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ(2) test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (κ = 0.50) and low for BVI (κ = 0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P = 0.001, P = 0.013, and IHC: P = 0.001, P = 0.019). The morphologic features associated with LVI were location of the tumor in the distal third of the stomach (P = 0.039), Borrmann's macroscopic type (P = 0.001), organ invasion (P = 0.03) and the depth of tumor invasion (P = 0.001). The presence of BVI was related only to the depth of tumor invasion (P = 0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.

Peritoneal carcinomatosis treated with cytoreductive surgery and intraperitoneal chemotherapy / Carcinomatose peritoneal tratada com cirurgia citoreductiva e quimioterapia intraperitoneal

ABSTRACT Introduction: To evaluate the combined treatment with cytoreductive surgery and intraperitoneal chemotherapy for peritoneal carcinomatosis arising from colorectal cancer, pseudomyxoma peritonei and mesothelioma. Methods: Data were obtained from 73 patients with peritoneal carcinomatosis arising from colorectal cancer (52.1%), pseudomyxoma peritonei (41.1%) or mesothelioma (6.8%) between 2002 and 2011. We reported the morbidity grade (II, III and IV), mortality and survival rates of the candidates after cytoreductive surgery and intraperitoneal chemotherapy. Results: 41 (56.2%) women participated, and the median age was 50 years. Thirty-nine patients (53.4%) underwent complete cytoreductive surgery and intraperitoneal chemotherapy. Patients who underwent a complete cytoreduction received intraperitoneal chemotherapy with mitomycin C, from which only 16/39 (41%) had hyperthermic intraperitoneal chemotherapy (41-42 °C). The overall morbidity rate was 23.3% and the grade III/IV complication rate was 12.3%. The overall mortality rate was 5.5%. The univariate analysis showed that cytoreductive surgery and intraperitoneal chemotherapy (p = .029), a blood transfusion (p = .002) and the operative time (p = .001) were significant for the occurrence of postoperative complications. Patients with peritoneal carcinomatosis from colorectal cancer who underwent complete cytoreductive surgery and intraperitoneal chemotherapy had overall survival rates of 81.3%, 12.5% and 12.5% at 1, 3 and 5 years, respectively. Patients with peritoneal carcinomatosis from pseudomyxoma peritonei who underwent complete cytoreductive surgery and intraperitoneal chemotherapy had overall survival rates of 84.2%, 77.7% and 77.7% at 1, 3 and 5 years, respectively. Conclusion: The combined treatment for peritoneal carcinomatosis may be performed safely with acceptable morbidity and mortality in a specialized unit setting. Although over half of patients underwent normothermic intraperitoneal chemotherapy, our results were comparable to results from others centers.

RESUMO Introdução: O objetivo foi avaliar o tratamento combinado da cirurgia citorredutora e quimioterapia intraperitoneal em pacientes com carcinomatose peritoneal secundária ao câncer colorretal, pseudomixoma peritoneal e mesotelioma. Métodos: Foram obtidos dados de 73 pacientes com carcinomatose peritoneal secundária ao cirurgia citorredutora (52.1%), pseudomixoma peritoneal (41,1%) ou mesotelioma (6,8%). Foram avaliados o grau de morbidade, a taxa de mortalidade e as taxas de sobrevida após a cirurgia citorredutora e quimioterapia intraperitoneal. Resultados: 41 (56,2%) pacientes do sexo feminino participaram, com média de idade de 50 anos. 39 pacientes (53,4%) foram submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal. Todos esses receberam Mitomicina C, sendo 16/39 (41%) quimioterapia intraperitoneal hipertérmica (41-42°C). A morbidade global foi 23,3%, com taxa de mortalidade global de 5,5%. A análise univariada mostrou que câncer colorretal e quimioterapia intraperitoneal (p = .029), transfusão sanguínea (p = .002) e tempo operatório (p = .001) foram associados com complicações pós-operatórias. Pacientes com carcinomatose peritoneal secundária ao cirurgia citorredutora submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal tiveram sobrevida global de 81,3%; 12,5% e 12,5% em 1, 3 e 5 anos, respectivamente. Os pacientes com pseudomixoma peritoneal que foram submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal tiveram sobrevida global de 84,2%; 77,7% e 77.7% em 1, 3 e 5 anos, respectivamente. Conclusão: O tratamento combinado para carcinomatose peritoneal é seguro quando realizado em centros terciários com experiência no procedimento. Embora mais da metade dos pacientes tenham sido submetidos a quimioterapia intraperitoneal normotérmica após a cirurgia citorredutora completa, os resultados podem ser comparados a de outros centros que utilizam exclusivamente a quimioterapia hipertérmica.

Expression of the c-MET, HGF and VEGF biomarkers in intestinal and diffuse gastric cancer in the Brazilian population: a pilot study for the standardization of the quantitative PCR technique

Background: Gastric carcinoma (GC) is the third leading cause of death among malignant tumors worldwide, causing approximately 900,000 deaths/year. Changes in oncogenes that encode tyrosine kinase receptors play an important role in the pathogenesis of GC. MET gene is a proto-oncogene that encodes a tyrosine kinase receptor c-MET and it is required for embryonic development and tissue repair. The hepatocyte growth factor (HGF) is the only known ligand for c-Met receptor. The MET oncogene activation suppresses apoptosis and promotes the survival, proliferation, migration, differentiation and angiogenesis of cells. Among the angiogenic factors, VEGF is the main regulator. Its biological function includes the promotion of endothelial cells mitosis to stimulate cells proliferation. These biomarkers expression in GC is relatively recent and population-based studies are required to define the expression pattern. The aim of this study was to determine qPCR technical standardization to evaluate quantitatively, in paraffin tissue samples, the presence of gene 23 expression of the MET, HGF and VEGF in diffuse and intestinal GC types. Methods: Twenty GC patients were studied, 10 patients were intestinal-type GC (average age 72.1 years) and 10 diffuse-type (average age 50.1 years). In all patients, tissue samples were analyzed from the tumor and distant areas of the tumor tissue. The relative expressions of the tumor markers c-Met, HGF and VEGF were performed by qPCR technique by comparing tumor and non-tumoral samples and they were normalized with the GAPDH constitutive gene. Statistical analysis was performed through T-test. Results: For c-Met, 18/20 (90%) patients expressed the marker and 9/20 (45%) overexpressed this gene, in which three were intestinal-type GC and six were diffuse-type GC. For HGF, only 7/20 (35%) patients expressed this gene and it was overexpressed in 4/20 (20%), in which two were intestinal-type GC and two were diffuse-type GC. For VEGF, 20/20 (100%) patients expressed this marker and in 12/20 (60%) were observed overexpression, in which eight patients had diffuse-type GC and four had intestinal-type GC. Conclusions: qPCR technique was standardized and suitable for expression analysis of the three biomarkers using paraffin embedded tissue samples. Further studies should be carried out to characterize the expression pattern of these biomarkers in GC in the Brazilian population (AU)

Impact of using a lymph node revealing solution in surgical specimens for pathological staging of gastric cancer / Uso de solução reveladora de linfonodos em peças cirúrgicas, no estadiamento anatomopatológico do câncer gástrico

Introduction: Lymph node (LN) metastasis is a major staging criterion of gastric cancer (GC). GC prognosis is associated with the number of metastatic LNs. Objectives: To evaluate the impact of using a lymph node revealing solution (LRS) in gastrectomy specimens. Materials and methods: prospective study in 30 gastrectomy specimens (19 men, average age of 59.5; 11 women, average age of 66.1) for pathological tumor, node, metastasis (TNM) staging. After LN dissection according to the routine procedures (conventional method [CM]), the tissue was emerged in LRS: a mixture containing 65% ethanol, 20% ether, 5% acetic acid, and 10% formalin solution (10%), for 36 hours with 3 changes. A new LN dissection was performed. The number of LNs obtained from both methods was compared and analyzed. The number of metastatic and non-metastatic LNs was determined. Results: From 1,005 (33.5/specimen) dissected LNs, 657 of which (21.9/specimen) by the CM, and 348 (11.6/specimen) after using LRS (p = 0.0002), metastases were detected in 272 LNs (9.2/case), 211 of which (7.0/specimen) were found with the CM, and 61 (2.0/specimen) after using LRS (p = 0.0028). The number of LNs increased 53.0% with LRS, and the number of metastatic LNs was 28.9% higher. The pN classification changed in 5 (16.7%) of the 30 specimens, and in stage grouping in 4 (13.3%) analyzed cases. Conclusion: The use of LRS in gastrectomy specimens is simple, enables dissection, increases the number of LNs, and occasionally changes pN staging and stage grouping. .

Introdução: O envolvimento do linfonodo (LNs) por metástase é importante critério para estadiar câncer gástrico (CG). Relaciona-se o prognóstico do CG com número de LNs metastáticos. Objetivos: Avaliar o impacto do uso de solução reveladora de linfonodos (SRL) em espécimes de gastrectomia. Materiais e métodos: Estudo prospectivo em 30 espécimes de gastrectomia (19 homens, média de idade 59,5 anos, e 11 mulheres, média de idade 66,1 anos) para estadiamento patológico tumor-linfonodo-metástase (TNM). Após dissecção dos LNs de acordo com procedimento de rotina (método convencional [MC]), esse tecido foi imerso em SRL, mistura contendo 65% de álcool, 20% de éter, 5% de ácido acético e 10% de formal a 10%, por 36 horas, com três mudanças, sendo realizada nova dissecção de LNs. Os LNs obtidos por ambos os métodos foram comparados e analisados. O número de LNs metastáticos e sem metástases foram determinados Resultados: Dissecados 1.005 LNs (33,5/caso): 657 LNs (21,9/caso) pelo MC e 348 LNs (11,6/caso) após uso da SRL (p = 0,0002). Metástases foram detectadas em 272 LNs (9,2/caso): 211 (sete/ caso) pelo MC e 61 (dois/caso) após uso de SRL (p = 0,0028). O uso da SRL aumentou o número de LNs em 53%, e o número de LNs metastáticos, em 28,9%. Houve mudança na classificação pN em cinco (16,7%) dos 30 espécimes, e no estadiamento por grupos em quatro (13,3%) casos analisados Conclusão: O uso de SRL em espécimes de gastrectomia é procedimento simples de aplicar, facilitando a dissecção, aumentando o número de LNs e eventualmente mudando estadiamento pN e de grupamento. .

The role of immunohistochemistry in the detection of vascular invasion in specimens of endoscopic submucosal dissection / O papel da imuno-histoquímica na detecção de invasão vascular em espécimes de dissecção endoscópica da submucosa

INTRODUCTION: Endoscopic submucosal dissection (ESD) of early neoplasias of the gastrointestinal tract (GIT) has been increasingly applied as an alternative to invasive surgical procedures, with the aim to preserve the patient's organ and quality of life, although it does not allow the histopathological analysis of lymph nodes. Previous studies demonstrated that the presence of neoplastic emboli in lymphatic (lymphatic vascular invasion [LVI]) or blood vessels (blood vascular invasion [BVI]) is considered a positive predictive factor for the occurrence of lymph node metastasis. The assessment of vascular invasion carried out only by routine hematoxylin and eosin staining (HE) may yield both falsepositive and false-negative results. D2-40 is a specific monoclonal antibody to the lymphatic endothelium. Thus, it is useful for identifying LVI and distinguishing if tumor embolization is found in blood or lymphatic vessels. OBJECTIVE: To determine the role of immunohistochemistry (IHC) in the assessment of ESD specimens by comparing the detection of LVI and BVI by HE and IHC with D2-40 and CD34 immunolabeling. METHOD: We conducted the IHC study using D2-40 and CD34 markers (pan-endothelial) in 30 cases of ESD with histological diagnosis of carcinoma in order to assess the presence of LVI and BVI. RESULTS: The detection of LVI was more prevalent than BVI. Three out of six cases with LVI were false-positive by HE and six were false-negative by IHC. Regarding BVI, five cases were identified and one was false-negative by IHC. CONCLUSION: Our results indicated that the histopathological analysis of ESD specimens by exclusively routine HE staining does not allow proper evaluation of BVI or LVI.

INTRODUÇÃO: A dissecção endoscópica da submucosa (DES) de neoplasias precoces do trato gastrointestinal (TGI) tem sido cada vez mais aplicada como alternativa aos procedimentos cirúrgicos invasivos, visando a preservar o órgão e a qualidade de vida do paciente, contudo, não possibilita a avaliação histopatológica de linfonodos. Estudos anteriores demonstraram que a presença de êmbolos neoplásicos, em vasos linfáticos (invasão vascular linfática [IVL]) ou sanguíneos (invasão vascular sanguínea [IVS]), é considerada um fator preditivo positivo para ocorrência de metástase linfonodal. A avaliação da invasão vascular realizada apenas pela coloração de rotina hematoxilina e eosina (HE) pode gerar resultados falso-positivos e falso-negativos. O D2-40 é um anticorpo monoclonal específico para endotélio linfático, sendo, portanto, útil para identificar IVL e distinguir se a embolização tumoral encontra-se em vasos sanguíneos ou linfáticos. OBJETIVO: Determinar o papel do estudo imuno-histoquímico (IHQ) na avaliação de espécimes de DES, comparando a detecção de IVL e IVS, pelo HE e IHQ com marcação por D2-40 e CD34. MÉTODO: Foi realizado estudo IHQ utilizando os marcadores D2-40 e CD34 (pan-endotelial) em 30 casos de produtos de DES com diagnóstico histológico de carcinoma para avaliar a presença de IVL e IVS. RESULTADOS: A detecção de IVL foi maior que a de IVS. Dos seis casos com IVL ao HE, três eram falso-positivos e seis, falso-negativos à IHQ. Em relação à IVS, foram identificados cinco casos falsopositivos e um falso-negativo à IHQ. CONCLUSÃO: Nossos resultados indicaram que a análise histopatológica dos produtos de DES realizando apenas a coloração HE não permite a avaliação adequada da presença de IVS ou IVL.

Actinomycosis mimicking colonic neoplasia

Actinomycosis is a rare inflammatory disease caused by Actinomyces israelii. It can mimic many other diseases, such as malignant neoplasms or inflammatory bowel disease. We present a case in which actinomycosis simulated a colonic neoplasia. (AU)

Actinomicose é uma doença inflamatória rara, causada pelo agente Actinomyces israelii. Pode mimetizar várias outras entidades, como neoplasias malignas e doenças inflamatórias intestinais. Relatamos aqui um caso, no qual a actinomicose simulou neoplasia cólica. (AU)

Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency.

BACKGROUND: Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. AIM: To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients. PATIENTS: Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied. METHODS: Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication. RESULTS: Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment. CONCLUSIONS: The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Câncer colorretal: resultados da avaliação patológica padronizada de 521 casos operados no Hospital das Clínicas da UFMG / Colorectal cancer: results of standardized pathologic evaluation of 521 patients underwent surgery at Hospital das Clínicas, Federal University of Minas Gerais

INTRODUÇÃO: A incidência e a mortalidade por câncer colorretal (CCR) têm apresentado, em todo mundo, uma tendência ao crescimento, em especial em países desenvolvidos e em áreas urbanas de países menos desenvolvidos. O estudo das características anatomopatológicas do tumor é importante para o estadiamento e a definição da terapêutica a ser empregada. O objetivo deste estudo é avaliar as características anatomopatológicas de peças cirúrgicas de ressecções colorretais por neoplasias no Hospital das Clínicas da Universidade Federal de Minas Gerais. RESULTADOS: Foram avaliadas 521 peças cirúrgicas de ressecções colorretais. A idade média dos pacientes foi de 62,47 (±14,67) anos, sendo 302 (58 por cento) deles do sexo feminino. Os tumores do cólon esquerdo foram os mais comuns (340 [65,3 por cento]). Houve predominância de adenocarcinomas (457 [87,7 por cento]), úlcero-infiltrativos (176 [33,8 por cento]), moderadamente diferenciados (396 [76 por cento]), pT3 (316 [60,7 por cento]) e pN0 (213 [40,9 por cento]). O número médio de linfonodos dissecados por peça cirúrgica foi de 22,13 (±14,27). CONCLUSÕES: Os dados de nossa casuística de CCR não diferiram do que foi relatado na literatura. Em síntese, o CCR foi mais comum em mulheres do que em homens, acometeu com maior frequência o cólon esquerdo, e o tipo predominante foi o adenocarcinoma moderadamente diferenciado, pT3 e pN0.

INTRODUCTION: The incidence and mortality of colorectal cancer (CRC) have shown, worldwide, an upward trend, particularly in developed countries and urban areas of developing countries. The study of tumor's pathological characteristics is important for staging and the definition of the proper therapy to be used. The aim of this study is to evaluate the pathologic features of surgical specimens of colorectal resections due CRC at Hospital das Clínicas, Universidade Federal de Minas Gerais. RESULTS: We evaluated 521 surgical specimens of colorectal resections. The mean age of patients was 62.47 (± 14.67) years, 302 (58 percent) were female. Tumors of the left colon were more common (340 [65.3 percent]). There was a predominance of adenocarcinoma (457 [87.7 percent]), ulcero-infiltrative (176 [33.8 percent]), moderately differentiated (396 [76 percent]), pT3 (316 [60.7 percent]) and pN0 (213 [40.9 percent]). The average number of dissected lymphonodes per surgical specimen was 22.13 (± 14.27). CONCLUSIONS: Data from our series of CRC did not differ from what was reported in the literature. In summary, the CRC was more common in women than in men, affecting most frequently the left colon, and the predominant type was moderately differentiated adenocarcinoma, pT3 and pN0.

Diferença entre hospitais privado e universitário na taxa de linfonodos de peça cirúrgica de câncer colorretal: o papel do patologista / Difference between university and private hospitals on lymph nodes harvest of surgical colorectal cancer specimens: the role of the pathologist

Tem sido demonstrado que o número de linfonodos obtidos em peças cirúrgicas de câncer colorretal é fundamental para o adequado estadiamento da doença e, consequentemente, para a obtenção de melhores resultados oncológicos. A percepção de diferenças no número de linfonodos dissecados em peças cirúrgicas de câncer colorretal pelos mesmos cirurgiões em hospitais diferentes motivou este estudo. O objetivo do presente estudo foi avaliar se há diferença no número de linfonodos e em determinados parâmetros histopatológicos em peça cirúrgica de pacientes com câncer colorretal operados por dois cirurgiões que atuam tanto em hospital universitário, como em hospital privado. MÉTODO: Foram avaliados retrospectivamente 122 pacientes, obtendo-se dados relativos a tipo de instituição (universitária versus privada), aspectos demográficos, estadiamento, localização do tumor, tipo de operação, via de acesso (aberta versus laparoscópica ), indicação de radioterapia, número de linfonodos dissecados, número de linfonodos positivos e negativos, assim como o tipo histológico, presença de invasões vascular, linfática e perineural e resposta linfocítica). RESULTADOS: Sessenta e cinco pacientes foram operados em instituição universitária e 57, em instituição privada. Não houve diferença entre os grupos quanto à idade, gênero, estadiamento, localização do tumor, indicação de radioterapia e tipo de operação. A via laparoscópica foi mais comum na instituição universitária. A mediana de linfonodos dissecados foi de 25 (P25-75: 15-34) na instituição universitária versus 15 (P25-75;12-17) (p<.0001). A média de linfonodos positivos foi de três na instituição universitária e de um na privada. O achado de 12 ou mais linfonodos foi mais comum em instituição universitária (55/64 versus 40/58; p=.024). A presença da informação de invasões linfática, vascular e perineural foi mais comum na instituição universitária. CONCLUSÃO: Mantendo a mesma técnica cirúrgica e com população...

It has been demonstrated that lymph nodes harvest from surgical specimens of colorectal cancer is one of the most important features for appropriate staging of the disease and to plain the best treatment. The perception of differences in the number of harvest lymph nodes in surgical specimens of colorectal cancer by the same surgeons in different hospitals motivated this investigation. The aims of this study was to assess whether there is difference in the number of lymph nodes and some histopathological features in surgical specimens of colorectal cancer obtained by two surgeons who work both in a university hospital and in a private one. METHODS: We retrospectively evaluated 122 patients, obtaining data on the type of institution (university or private), demographic features, staging, tumor site, histological type, open or laparoscopic access, indication of radiotherapy, number of harvest lymph nodes, presence of vascular, lymphatic and neural invasions. RESULTS: Sixty-five patients were operated in a university institution and 57 in two private institutions. There was no difference between groups in terms of age, stage, tumor site, details of radiotherapy and type of operation. The laparoscopic route was more common in the university institution. The median of lymph nodes harvested was 25 (P25-75: 15-34) in the university institution and 15 in the private ones (P25-75, 12-17) (p <.0001). The finding of 12 or more lymph nodes was more common in academic institution (55/65 versus 40/57, p =. 024). The presence of information of lymphatic, vascular and perineural invasion was more common in the university institution. CONCLUSION: Keeping the same surgical technique and with comparable population of patients, there was considerable difference in the number of lymph nodes harvested between university and private institutions, as like as the report of other relevant data for the histopathological staging, which impacts indication for adjuvant...

Análise de 33 peças cirúrgicas de colectomias laparoscópicas para câncer, durante a curva de aprendizado inicial: margens oncológicas e número de linfonodos não diferem de colectomias abertas / Analysis of 33 surgical specimens of laparoscopic resections for colorectal cancer in the early learning curve: margins and nodes harvest do not differ from open resections

INTRODUÇÃO: A colectomia laparoscópica é considerada um procedimento com longa curva de aprendizado. Apesar de cirurgiões experientes em laparoscopia apresentarem resultados oncológicos semelhantes aos de colectomias abertas, é importante avaliar se durante a curva de aprendizado esses resultados também podem ser alcançados. O objetivo deste trabalho foi avaliar as margens de ressecção e o número de linfonodos obtidos nas peças cirúrgicas dos casos iniciais de colectomias laparoscópicas realizadas por cirurgiões especialistas, comparando-os com colectomias abertas. MÉTODOS: Foram avaliadas as peças cirúrgicas dos 33 primeiros casos de colectomias laparoscópicas para câncer colorretal. As seguintes variáveis foram analisadas: idade, gênero, localização do tumor, classificação anátomo-patológica, número de linfonodos e margens proximal e distal. Os dados foram comparados com grupo controle de 45 pacientes submetidos a colectomia aberta para câncer colorretal. Foram utilizados os testes estatísticos qui-quadrado , teste t de Student e Mann-Whitney. RESULTADOS: Os grupos laparoscópico e aberto foram semelhantes em relação à idade, localização do tumor e estadiamento loco-regional. O grupo laparoscópico apresentou predominância do sexo feminino. As margens cirúrgicas distais foram semelhantes nos dois grupos [média de 7,15 cm (DP ± 9,98) e 8,26 cm (DP ± 11,5) para os grupos aberto e laparoscópico, respectivamente, p=NS]. O número de linfonodos por peça cirúrgica também não apresentou diferença entre os grupos. A média de linfonodos para o grupo aberto e laparoscópico foram 19 (DP ± 19,41) e 21 (DP ± 14,73) respectivamente, (p=NS). CONCLUSÃO: Não houve diferença entre as margens oncológicas e o número de linfonodos quando comparadas peças cirúrgicas de colectomias laparoscópicas durante a curva de aprendizado com peças de colectomias abertas. Apesar da dificuldade técnica comumente observada no início da experiência com colectomia laparoscópica...

INTRODUCTION: Colorectal laparoscopic surgery is considered a procedure with long learning curve. Despite surgeons with experience in laparoscopic surgery are able to achieve the same oncological results obtained in open procedures, it is important to evaluate if these good results are sustained during the learning curve. The aim of this study was to evaluate the adequacy of the margins and the lymph nodes harvest in early learning curve of laparoscopic colectomies performed by specialized surgeons compared to open colectomies. METHODS: Thirty-three surgical specimens of laparoscopic resections for colorectal cancer performed during the early learning curve were evaluated. The following data were analyzed: age, sex, tumor location, pathologic classification, lymph node harvest and proximal and distal margins. Data were compared to a control group of 45 open resections for colorectal cancer. RESULTS: Age, tumor location and Dukes classification of laparoscopic and open groups were similar. Laparoscopic group had more female patients. Distal margins were similar between the groups [mean of 7,15 cm (SD ± 9,98) for open and 8,26 cm (SD ± 11,5) for laparoscopic group, p=NS]. There was no difference in the lymph nodes harvest between the groups. The mean of lymph nodes harvest of open and laparoscopic groups were 19 (SD ± 19,41) and 21 (SD ± 14,73), respectively, (p=NS). CONCLUSION: Oncologic margins and lymph nodes harvest obtained during early learning curve of laparoscopic resections were similar to open procedures. Despite the natural difficulties faced during early learning curve, oncologic criteria can be achieved when laparoscopic colorectal resections are performed by specialized surgeons working with gastrointestinal pathology team.

Impacto do uso da solução reveladora de linfonodos no estadiamento do câncer colorretal / Impact of the use of fat clearance solution in the harvest of lymph nodes and the staging of colorectal cancer

INTRODUÇÃO: A avaliação anátomo-patológica do câncer colorretal (CCR) em relação ao acometimento linfonodal é fundamental para o prognóstico da doença e para a indicação de terapias adjuvantes. Tem sido considerado um número mínimo de 12 linfonodos na peça cirúrgica para que se obtenha adequado estadiamento linfonodal, embora se admita que quanto maior o número de linfonodos dissecados, maior é a probabilidade de se encontrar linfonodos metastáticos. OBJETIVOS: avaliar o número de linfonodos obtidos em peças cirúrgicas de CCR antes e após a utilização rotineira de solução reveladora de linfonodos na gordura mesocólica. MATERIAL E MÉTODOS: Foram avaliados 706 laudos anátomo-patológicos de CCR, sendo 582 sem tratamento do espécime cirúrgico com solução reveladora e 124 após uso de solução reveladora. Resultados: Houve predominância do sexo feminino (57,6 por cento) e a média de idade foi de 61,36 anos. A maioria dos tumores localizava-se distalmente à flexura esplênica (60 por cento). A média de linfonodos dissecados após uso da solução reveladora foi igual a 28,97, enquanto que no período anterior ao uso desta solução esta média foi de 16,73 (p < 0,001). A porcentagem de peças com 11 linfonodos dissecados ou menos (pNx) diminuiu significativamente após a utilização da solução reveladora (32,7 para 3,2 por cento, com p < 0,0001). Ao contrário, houve aumento significativo do número de casos estadiados como pN0, pN1, pN2 e pN3 após o uso da solução reveladora. CONCLUSÃO: O uso da solução reveladora de linfonodos causa grande impacto no estudo anátomo-patológico das peças cirúrgicas do CCR, sendo altamente aconselhável sua introdução na rotina dos serviços de patologia cirúrgica.

INTRODUCTION: Accurate pathological study of colorectal cancer (CRC) specimens is of paramount importance to prognosis and indication of adjuvant therapies. Despite the minimum of 12 lymph nodes has been considered adequate to correctly establish the stage of disease, a bigger harvest of lymph nodes would increase the number of metastatic lymph nodes obtained. AIMS: To evaluate the harvest of lymph nodes from mesocolic fat before and after the introduction of routine use of a revealing solution of lymph nodes. Methods: We evaluated a total of 706 pathological reports of CRC, 582 without use of revealing solution and 124 with use of this solution. RESULTS: most of patients were females (57.6 percent) with mean age of 61.36 years. Sixty per cent of tumors were located distally to splenic flexure. The average of lymph nodes obtained was 16.73 and 28.97 before and after use of revealing solution, respectively (p < 0,001). Percentage of specimens with eleven or less lymph nodes (Nx) decreased significantly after use of revealing solution (32.7 to 3.2 percent; p < 0,0001). In opposite, there was a significative increase in number of cases sorted as pN0, pN1, pN2 e pN3 after use of revealing solution. CONCLUSION: The use of revealing solution of lymph nodes causes great impact in the pathological study of CRC and its routine use is strongly recommended in the surgical pathology services.

Association of the presence of Helicobacter in gallbladder tissue with cholelithiasis and cholecystitis.

The presence of Helicobacter DNA species has been investigated in the biliary epithelium of patients with biliary diseases. However, conflicting results have been observed that may have been due to the small number of subjects studied, difficulty in obtaining a healthy control group, absence of controlling for confounding factors, or differences among populations. Therefore, we investigated the presence of Helicobacter species by culture and nested PCR of 16S rRNA genes in gallbladder tissue and bile from 46 Brazilian subjects with and 18 without cholelithiasis. The control group was mainly composed of liver donors and of patients who had submitted to cholecystectomy as part of the surgical treatment for morbid obesity. No Helicobacter species were grown from the bile or gallbladder tissues. Helicobacter DNA was detected in the gallbladder tissue and bile from 31.3 and 42.9% of the patients, respectively. In a logistic regression model, cholelithiasis was positively and independently associated with the female gender (P = 0.02), increasing age (P = 0.002), and the presence of Helicobacter DNA in the gallbladder tissue (P = 0.009). The presence of Helicobacter DNA in the bile was not associated with cholelithiasis (P = 0.8). A significant association between the presence of Helicobacter DNA in the gallbladder epithelium and histological cholecystitis, even after adjusting for gender and age (P = 0.002), was also observed. The sequences of the 16S rRNA genes were >99% similar to that of Helicobacter pylori. In conclusion, our results support the hypothesis that Helicobacter is associated with the pathogenesis of human cholelithiasis and cholecystitis.

babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil.

The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.

Role of corpus gastritis and cagA-positive Helicobacter pylori infection in reflux esophagitis.

Considering that the role of Helicobacter pylori infection in gastroesophageal reflux and reflux esophagitis (GERD) is still controversial and that the role of virulence markers of the bacterium has not been evaluated in most studies of GERD, we investigated the association among H. pylori infection with cagA-positive and -negative strains, corpus gastritis, and GERD in a large group of patients by controlling for confounding factors. We studied prospectively 281 consecutive adult patients: 93 with GERD and 188 controls. H. pylori infection status was diagnosed by culture, by the preformed urease test, with a carbolfuchsin-stained smear, and by histology. The cagA status was determined by PCR of H. pylori isolates and gastric biopsy specimens. H. pylori infection was diagnosed in 191 (68.0%) of 281 patients. Among the 93 patients with GERD, 84 presented with mild or moderate esophagitis and 9 presented with severe esophagitis. In the multivariate analysis, the age of the patients and the degree of oxyntic gastritis were associated with GERD. Among the strains isolated from patients with GERD and from the control group, 24.4 and 66.9%, respectively, were positive for cagA (P < 0.001). Compared to infection with cagA-negative strains, infection with cagA-positive H. pylori strains was associated with a more intense gastritis in the corpus (P = 0.001). cagA status (odds ratio [OR] = 0.16, 95% confidence interval [CI] = 0.07 to 0.40), gastritis of the corpus (OR = 0.69, 95% CI = 0.48 to 0.99), and age (OR = 1.04, 95% CI = 1.01 to 1.07) were associated with GERD. In conclusion, the study provides evidence supporting the independent protective roles of cagA-positive H. pylori strains and the degree of corpus gastritis against GERD.

IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis.

BACKGROUND & AIMS: Proinflammatory interleukin (IL)-1 gene polymorphisms associated with high levels of IL-1beta activity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether carriers of these polymorphic genes are protected against gastroesophageal reflux disease (GERD). TNFA-308 polymorphisms were also studied. METHODS: We prospectively evaluated 385 patients without gastric cancer and peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were successfully genotyped for all cytokines studied. The cagA status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31, IL1RN, and TNFA-308 polymorphisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was assessed according to the updated Sydney system. The role of the proinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controlling for confounding factors. RESULTS: IL1B-31 (a near-complete linkage disequilibrium between polymorphism at -31 and -511 was found) and IL1RN*2 allele polymorphisms were associated with GERD. After stratification, in the group of H. pylori-positive patients, cagA-positive status, IL1B-31 polymorphic alleles, IL1RN*2 alleles, and the degree of corpus gastritis were negatively associated with GERD. In the H. pylori-negative group, IL1B-31C/C genotype was inversely associated with GERD even after adjustment for age and sex. CONCLUSIONS: This study provides evidence supporting the independent protective role of cagA-positive H. pylori status and IL1B and ILRN allele polymorphisms against GERD.