BRAZILIAN CONSENSUS ON INCIDENTAL GALLBLADDER CARCINOMA.

BACKGROUND: Incidental gallbladder cancer is defined as a cancer discovered by histological examination after cholecystectomy. It is a potentially curable disease. However, some questions related to their management remain controversial and a defined strategy is associated with better prognosis. AIM: To develop the first evidence-based consensus for management of patients with incidental gallbladder cancer in Brazil. METHODS: Sixteen questions were selected, and 36 Brazilian and International members were included to the answer them. The statements were based on current evident literature. The final report was sent to the members of the panel for agreement assessment. RESULTS: Intraoperative evaluation of the specimen, use of retrieval bags and routine histopathology is recommended. Complete preoperative evaluation is necessary and the reoperation should be performed once final staging is available. Evaluation of the cystic duct margin and routine 16b1 lymph node biopsy is recommended. Chemotherapy should be considered and chemoradiation therapy if microscopically positive surgical margins. Port site should be resected exceptionally. Staging laparoscopy before reoperation is recommended, but minimally invasive radical approach only in specialized minimally invasive hepatopancreatobiliary centers. The extent of liver resection is acceptable if R0 resection is achieved. Standard lymph node dissection is required for T2 tumors and above, but common bile duct resection is not recommended routinely. CONCLUSIONS: It was possible to prepare safe recommendations as guidance for incidental gallbladder carcinoma, addressing the most frequent topics of everyday work of digestive and general surgeons.

Brazilian consensus on incidental gallbladder carcinoma / Consenso brasileiro de carcinoma incidental de vesícula biliar

ABSTRACT Background: Incidental gallbladder cancer is defined as a cancer discovered by histological examination after cholecystectomy. It is a potentially curable disease. However, some questions related to their management remain controversial and a defined strategy is associated with better prognosis. Aim: To develop the first evidence-based consensus for management of patients with incidental gallbladder cancer in Brazil. Methods: Sixteen questions were selected, and 36 Brazilian and International members were included to the answer them. The statements were based on current evident literature. The final report was sent to the members of the panel for agreement assessment. Results: Intraoperative evaluation of the specimen, use of retrieval bags and routine histopathology is recommended. Complete preoperative evaluation is necessary and the reoperation should be performed once final staging is available. Evaluation of the cystic duct margin and routine 16b1 lymph node biopsy is recommended. Chemotherapy should be considered and chemoradiation therapy if microscopically positive surgical margins. Port site should be resected exceptionally. Staging laparoscopy before reoperation is recommended, but minimally invasive radical approach only in specialized minimally invasive hepatopancreatobiliary centers. The extent of liver resection is acceptable if R0 resection is achieved. Standard lymph node dissection is required for T2 tumors and above, but common bile duct resection is not recommended routinely. Conclusions: It was possible to prepare safe recommendations as guidance for incidental gallbladder carcinoma, addressing the most frequent topics of everyday work of digestive and general surgeons.

RESUMO Racional: Carcinoma incidental da vesícula biliar é definido como uma neoplasia descoberta por exame histológico após colecistectomia videolaparoscópica. É potencialmente uma doença curável. Entretanto algumas questões relacionadas ao seu manuseio permanecem controversas e uma estratégia definida está associada com melhor prognóstico. Objetivo: Desenvolver o primeiro consenso baseado em evidências para o manuseio de pacientes com carcinoma incidental da vesícula biliar no Brasil. Métodos: Dezesseis questões foram selecionadas e para responder as questões e 36 membros das sociedades brasileiras e internacionais foram incluídos. As recomendações foram baseadas em evidências da literatura atual. Um relatório final foi enviado para os membros do painel para avaliação de concordância. Resultados: Avaliação intraoperatória da peça cirúrgica, uso de bolsas para retirar a peça cirúrgica e exame histopatológico de rotina, foram recomendados. Avaliação pré-operatória completa é necessária e deve ser realizada assim que o estadiamento final esteja disponível. Avaliação da margem do ducto cístico e biópsia de rotina do linfonodo 16b1 são recomendadas. Quimioterapia deve ser considerada e quimioradioterapia indicada se a margem cirúrgica microscópica seja positiva. Os portais devem ser ressecados excepcionalmente. O estadiamento laparoscópico antes da operação é recomendado, mas o tratamento radical por abordagem minimamente invasiva deve ser realizado apenas em centros especializados em cirurgia hepatopancreatobiliar minimamente invasiva. A extensão da ressecção hepática é aceitável até que seja alcançada a ressecção R0. A linfadenectomia padrão é indicada para tumores iguais ou superiores a T2, mas a ressecção da via biliar não é recomendada de rotina. Conclusões: Recomendações seguras foram preparadas para carcinoma incidental da vesícula biliar, destacando os mais frequentes tópicos do trabalho diário do cirurgião do aparelho digestivo e hepatopancreatobiliar.

KRAS mutation status is highly homogeneous between areas of the primary tumor and the corresponding metastasis of colorectal adenocarcinomas: one less problem in patient care.

Background: Mutations in KRAS are negative predictors of the response to anti-EGFR therapies in the treatment of metastatic colorectal cancer. Yet, the ideal tissue to test for KRAS mutation-primary or metastatic-remains unknown, as is the validity of testing only 1 area of the primary tumor. The aim of this study was to determine the heterogeneity of KRAS mutational status between areas of the primary lesion and between paired primary CRC and the corresponding lymph node (LN), liver, and lung metastasis with a high-sensitivity sequencing method. Design: DNA from 2 or 3 areas from the primary tumor and 1 area of metastatic tissue was obtained from formalin-fixed paraffin-embedded specimens from 102 metastatic CRC patients. Mutations in KRAS codons 12, 13, and 61 were analyzed by pyrosequencing. RESULTS: Ninety-one cases had DNA extracted from more than 1 area of the primary tumor. Only 1 patient showed intratumor heterogeneity, which involved KRAS mutation type, not KRAS mutational status. We examined KRAS mutations in 97 primaries and matched metastatic samples, recording 2 discordant cases, representing 2.1% of our cohort of matched samples. Conclusion:KRAS status is highly homogeneous throughout primary CRC tumor areas and consistent between the primary tumor and metastatic tissue in the same patient. Our data suggest that testing KRAS mutations in only 1 area of the primary or metastatic tissue is suitable for predicting the response to anti-EGFR treatment and guiding clinical decisions.

Resection of liver metastasis from neuroendocrine tumors: evaluation of results and prognostic factors.

OBJECTIVES: to determine the prognostic factors that may impact on morbidity and mortality and survival of patients undergoing surgical treatment of liver metastases from neuroendocrine tumors. METHODS: We studied 22 patients undergoing liver resection for metastases from neuroendocrine tumors between 1997 and 2007. Epidemiological and clinical data were correlated with morbidity and mortality and overall and disease-free survivals. RESULTS: twelve patients were male and ten female, with a mean age of 48.5 years. Bilobar disease was present in 17 patients (77.3%). In ten patients (45.5%) the primary tumor originated in the pancreas, terminal ileum in eight, duodenum in two, rectum in one and jejunum in one. Complete surgical resection (R0) was achieved in 59.1% of patients. Eight patients (36.3%) developed complications in the immediate postoperative period, one of them dying from septicemia. All patients undergoing re-hepatectomy and/or two-stage hepatectomy had complications in the postoperative period. The overall survival at one and five years was 77.3% and 44.2%. The disease-free survival at five years was 13.6%. The primary pancreatic neuroendocrine tumor (p = 0.006) was associated with reduced overall survival. Patients with number of metastatic nodules < 10 (p = 0.03) and asymptomatic at diagnosis (p = 0.015) had higher disease-free survival. CONCLUSION: liver metastases originating from pancreatic neuroendocrine tumors proved to be a negative prognostic factor. Symptomatic patients with multiple metastatic nodules showed a significant reduction in disease-free survival.

Resection of liver metastasis from neuroendocrine tumors: evaluation of results and prognostic factors / Ressecção de metástases hepáticas de tumores neuroendócrinos: avaliação dos resultados e fatores prognósticos

OBJECTIVES: To determine the prognostic factors that may impact on morbidity and mortality and survival of patients undergoing surgical treatment of liver metastases from neuroendocrine tumors. METHODS: We studied 22 patients undergoing liver resection for metastases from neuroendocrine tumors between 1997 and 2007. Epidemiological and clinical data were correlated with morbidity and mortality and overall and disease-free survivals. RESULTS: twelve patients were male and ten female, with a mean age of 48.5 years. Bilobar disease was present in 17 patients (77.3%). In ten patients (45.5%) the primary tumor originated in the pancreas, terminal ileum in eight, duodenum in two, rectum in one and jejunum in one. Complete surgical resection (R0) was achieved in 59.1% of patients. Eight patients (36.3%) developed complications in the immediate postoperative period, one of them dying from septicemia. All patients undergoing re-hepatectomy and/or two-stage hepatectomy had complications in the postoperative period. The overall survival at one and five years was 77.3% and 44.2%. The disease-free survival at five years was 13.6%. The primary pancreatic neuroendocrine tumor (p = 0.006) was associated with reduced overall survival. Patients with number of metastatic nodules < 10 (p = 0.03) and asymptomatic at diagnosis (p = 0.015) had higher disease-free survival. CONCLUSION: liver metastases originating from pancreatic neuroendocrine tumors proved to be a negative prognostic factor. Symptomatic patients with multiple metastatic nodules showed a significant reduction in disease-free survival.

OBJETIVOS: Determinar fatores prognósticos com possível impacto na morbimortalidade e sobrevida de pacientes submetidos ao tratamento cirúrgico das metástases hepáticas de tumores neuroendócrinos. MÉTODOS: foram estudados 22 pacientes submetidos à ressecção hepática por metástases de tumores neuroendócrinos entre 1997 e 2007. Dados epidemiológicos e clínicos foram correlacionados com morbimortalidade e sobrevidas global e livre de doença. RESULTADOS: doze pacientes eram do sexo masculino e dez do feminino com média de idade de 48,5 anos. Doença bilobar esteve presente em 17 pacientes (77,3%). Em dez pacientes (45,5%) o tumor primário se originou no pâncreas, em oito no íleo terminal, em dois no duodeno, em um no reto e em um no jejuno. Ressecção cirúrgica completa (R0) foi alcançada em 59,1% dos pacientes. Oito pacientes (36,3%) evoluíram com complicações no pós-operatório imediato, com um paciente evoluindo ao óbito por septicemia. Todos os pacientes submetidos à re-hepatectomia e/ou hepatectomia em dois tempos evoluíram com complicações no período pós-operatório. A sobrevida global em um e cinco anos foi 77,3% e 44,2%. A sobrevida livre de doença em cinco anos foi 13,6%. O tumor neuroendócrino primário do pâncreas (p=0,006) foi associado à redução na sobrevida global. Os pacientes com número de nódulos metastáticos <10 (p=0,03) e os assintomáticos ao diagnóstico (p=0,015), apresentaram maior sobrevida livre de doença. CONCLUSÃO: metástases hepáticas oriundas de tumores neuroendócrinos pancreáticos demonstraram ser um fator prognóstico negativo. Pacientes sintomáticos e com múltiplos nódulos metastáticos apresentam redução significativa na sobrevida livre de doença.