ABSTRACT
Esophageal cancer is an aggressive tumor that has a high rate of incidence and mortality worldwide. It is the 10th most frequent type in Brazil, being squamous cell carcinoma (ESCC) the predominant subtype. There is currently an incessant search to identify the frequently altered genes associated with esophageal squamous cell carcinoma biology that could be druggable. This study aimed to analyze the somatic mutation profile of a large panel of cancer-related genes in Brazilian ESCC. In a series of 46 ESCC diagnoses at Barretos Cancer Hospital, DNA isolated from paired fresh-frozen and blood tissue, a panel of 150 cancer-related genes was analyzed by next-generation sequencing. The genes with the highest frequency of mutations were TP53 (39/46, 84.8%), followed by NOTCH1 (7/46, 15.2%), NFE2L2 (5/46, 10.8%), RB1 (3/46, 6.5%), PTEN (3/46, 6.5%), CDKN2A (3/46, 6.5%), PTCH1 (2/46, 4.3%) and PIK3CA (2/46, 4.3%). There was no significant association between molecular and patients' clinicopathological features. Applying an evolutionary action score of p53 (EAp53), we observed that 14 (35.9%) TP53 mutations were classified as high-risk, yet no association with overall survival was observed. Concluding, this the largest mutation profile of Brazilian ESCC patients, which helps in the elucidation of the major cancer-related genes in this population.
Subject(s)
Esophageal Squamous Cell Carcinoma/epidemiology , Esophageal Squamous Cell Carcinoma/genetics , Transcriptome/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Brazil/epidemiology , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Female , Gene Expression/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/genetics , Genomics/methods , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation/geneticsABSTRACT
BACKGROUND: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. AIM: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. METHODS: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. CONCLUSION: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.
Subject(s)
Stomach Neoplasms , Brazil , Consensus , Gastrectomy , Humans , Lymph Node Excision , Stomach Neoplasms/surgeryABSTRACT
ABSTRACT Background : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. Aim : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. Methods: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. Results : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. Conclusion : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.
RESUMO Racional: O II Consenso Brasileiro de Câncer Gástrico da Associação Brasileira de Câncer Gástrico ABCG (Parte 1) foi recentemente publicado. Nesta ocasião inúmeros especialistas que atuam no tratamento desta doença expressaram suas opiniões diante declarações apresentadas. Objetivo: Apresentar as Diretrizes da ABCG (Parte 2) quanto às indicações de tratamento cirúrgico, técnicas operatórias, extensão de ressecção e terapia combinada. Métodos: Para formulação destas diretrizes os autores realizaram extensa e atual revisão referente a cada declaração presente no II Consenso, utilizando as bases Medline/PubMed, Cochrane Library e SciELO, inicialmente com os seguintes descritores: câncer gástrico, gastrectomia, linfadenectomia, terapia combinada. Ainda, cada declaração foi classificada de acordo com o nível de evidência e grau de recomendação. Resultados: Das 43 declarações presentes neste estudo, 11 (25,6%) foram classificadas com nível de evidência A, 20 (46,5%) B e 12 (27,9%) C. Quanto ao grau de recomendação, 18 (41,9%) declarações obtiveram grau de recomendação 1, 14 (32,6%) 2a, 10 (23,3%) 2b e um (2,3%) 3. Conclusão: O complemento das diretrizes aqui presentes possibilita que cirurgiões e oncologistas que atuam no combate ao câncer gástrico possam oferecer o melhor tratamento possível, de acordo com as condições locais disponíveis.
Subject(s)
Humans , Stomach Neoplasms/surgery , Brazil , Consensus , Gastrectomy , Lymph Node ExcisionABSTRACT
BACKGROUND: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented. AIM: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients. METHODS: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3. CONCLUSION: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.
Subject(s)
Endoscopy, Digestive System , Neoplasm Staging , Stomach Neoplasms , Brazil , Consensus , Follow-Up Studies , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgerySubject(s)
Gallbladder Neoplasms/surgery , Laparoscopy/methods , Robotic Surgical Procedures/methods , Adult , Cholecystectomy , Female , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: This study addressed whether the positive node-ratio (N-ratio) for patients who underwent curative-intent treatment was an independent prognostic factor of overall survival (OS) for gastric adenocarcinoma (GA). METHODS: Consecutive patients who underwent gastrectomy for GA with at least 15 harvested nodes were evaluated for 5-year OS. The best threshold was determined using the area under an receiver operating characteristic (ROC) curve. Univariate and multivariate models were assessed looking for independent prognostic factors for OS. RESULTS: From 1994 to 2015, 398 consecutive patients were evaluated. The N-ratio ≥11% had an accuracy of 0.764, the sensitivity of 71.1%, the specificity of 81.7%, positive predictive value (PPV) of 91.7%, and odds ratio (OR) of 11. After multivariate analysis for OS, age ≥70 years (HR 1.44), need for total gastrectomy (HR 1.45), need for extended resection (HR 1.7), and N-ratio ≥11% (HR 3.7) were unfavorable prognostic factors. D2 lymphadenectomy (HR 0.53) was a protective factor. The median OS according to N-ratio was 14 months for N-ratio >11 vs 58 months for N-ratio <11%. CONCLUSION: The N-ratio ≥11% was an independent negative prognostic factor for patients who underwent treatment for GA with curative intent. The N-ratio ≥11% presented high specificity, high PPV and high OR for risk of death for 5 years after surgery.
Subject(s)
Adenocarcinoma/mortality , Lymph Node Excision , Lymph Nodes/pathology , Stomach Neoplasms/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Female , Gastrectomy , Humans , Lymphatic Metastasis , Male , Predictive Value of Tests , Prognosis , Retrospective Studies , Sensitivity and Specificity , Stomach Neoplasms/pathology , Stomach Neoplasms/surgeryABSTRACT
ABSTRACT Background: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. Aim: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. Methods: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. Results: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. Conclusion: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.
RESUMO Racional: Desde a publicação do primeiro Consenso Brasileiro sobre Câncer Gástrico em 2012 realizado pela Associação Brasileira de Câncer Gástrico (ABCG), novos conceitos sobre o diagnóstico, estadiamento, tratamento e seguimento foram incorporados. Objetivo: Promover uma atualização aos profissionais que atuam no combate ao câncer gástrico (CG) e fornecer diretrizes quanto ao manejo dos pacientes portadores desta afecção. Métodos: Cinquenta e nove especialistas responderam 67 declarações sobre o diagnóstico, estadiamento, tratamento e prognóstico do CG com cinco alternativas possíveis: 1) concordo plenamente; 2) concordo parcialmente; 3) indeciso; 4) discordo e 5) discordo fortemente. Foi considerado consenso a concordância de pelo menos 80% da soma das respostas "concordo plenamente" e "concordo parcialmente". Este artigo apresenta apenas as respostas dos especialistas participantes. Os comentários sobre cada declaração, assim como uma revisão da literatura serão apresentados em publicações futuras. Resultados: Das 67 declarações, houve consenso em 50 (74%). Em 10 declarações, houve concordância de 100%. Conclusão: O tratamento do câncer gástrico evoluiu consideravelmente nos últimos anos. Este consenso reúne princípios consolidados nas últimas décadas, novos conhecimentos adquiridos recentemente, assim como perspectivas promissoras sobre o manejo desta doença.
Subject(s)
Humans , Stomach Neoplasms , Societies, Medical , Brazil , ConsensusABSTRACT
BACKGROUND: The extension of lymphadenectomy for GA remains on debate even after Eastern and Western clinical trials. The main concern is if morbidity of extended lymphadenectomy could be justified based on benefits in oncologic outcomes. This study addressed the extension of lymphadenectomy as a prognostic factor of overall survival (OS) for gastric adenocarcinoma (GA). METHODS: Consecutive patients who underwent gastrectomy for GA were retrospectively evaluated. Univariate and multivariate models assessed determinants of OS. RESULTS: From 1994 to 2015, 656 consecutive patients who underwent gastrectomy were evaluated. Briefly, 455 (69.4%) were male, 397 (60.5%) underwent total gastrectomy, Roux-en-Y reconstruction was done in 483 (73.6%), and R0 resection was achieved in 632 patients (96.3%). According to multivariate analysis, the risk of death was increased with older age (≥70-y), high-grade tumors, lesionsâ¯≥â¯5â¯cm, positive nodesâ¯≥â¯3, and extra-gastric resections. Otherwise, D2 lymphadenectomy improved median OS (37 versus 16 months), 3-y (51.1 versus 32.2%), 5-y (43.2 versus 26), and 10-y OS (30.6 versus 9.4%), with HR of 0.48 (95% CI 0.34-0.67, pâ¯<â¯0.001). The general median OS was 31 months and 3-, 5-, and 10-y were 47.6, 40, and 27%, respectively. The median follow-up for all patients was 26 months, and for survivors was 65 months. CONCLUSION: This study showed D2 lymphadenectomy for GA as an independent prognostic factor for OS, even after 5-y and until 10-y. Our study suggests that D2 should be offered as the curative-intent treatment for all patients with GA that fit to undergo surgery.
Subject(s)
Adenocarcinoma/secondary , Forecasting , Lymph Node Excision/methods , Lymph Nodes/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Aged , Brazil/epidemiology , Female , Follow-Up Studies , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Survival Rate/trendsABSTRACT
Laparoscopy is considered the gold standard approach to perform left lateral sectionectomy (LLS). Furthermore, laparoscopy for cirrhotic patients can reduce intraoperative bleeding and postoperative morbidity when compared to open surgery. Although robotic surgery is feasible for both minor and major liver resections, it remains a work in progress and only few series reported this approach for cirrhotic patients. We reported two cases of 62-year-old men, both with hepatitis C virus and alcoholic cirrhosis, but with compensated liver functions (MELD 9-10 and Child-Pugh A5-A6). The patients were diagnosed with a single lesion in the left lobe. Robotic LLS was performed using intraoperative ultrasound to confirm findings of pre-operative image, and linear staplers were used to control left lobe inflow and outflow. The specimens were removed through Pfannenstiel incision in both patients. Both procedures followed the same standardization. The total operative time was 250 and 151 min with estimated blood loss of 100 and 70 ml, respectively, for cases 1 and 2. The procedures were made without Pringle maneuver and postoperative course was uneventful with hospital discharge at third and fourth postoperative day, respectively. The pathology examination confirmed a 2.5- and 4.5-cm hepatocellular carcinoma, respectively; both presented negative margins and cirrhosis. Robotic LLS seems to be as feasible as conventional laparoscopic approach as a stepwise procedure in a robotic learning curve for liver resection. Its benefits can also be offered to selected cirrhotic patients.
Subject(s)
Hepatectomy/methods , Hepatitis C/surgery , Liver Cirrhosis, Alcoholic/surgery , Minimally Invasive Surgical Procedures/methods , Robotic Surgical Procedures/methods , Humans , Liver/surgery , Male , Middle AgedABSTRACT
BACKGROUND: There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer. METHODS: This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. RESULTS: Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence. CONCLUSIONS: According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors.
Subject(s)
ErbB Receptors/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Humans , Kaplan-Meier Estimate , Middle Aged , Models, Statistical , Predictive Value of Tests , Prognosis , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/metabolism , Receptor, ErbB-4 , Retrospective Studies , Stomach Neoplasms/surgery , SurvivorsABSTRACT
BACKGROUND: Adjuvant chemoradiotherapy (CRT) is the standard treatment in Western countries for gastric cancer patients submitted to curative resection. However, the role of adjuvant CRT in gastric cancer treated with D2 lymphadenectomy has not been well defined. METHODS: We conducted a retrospective study in patients with stage II to IV gastric adenocarcinoma with no distant metastases, who underwent curative resection with D2 lymphadenectomy between January 2002 and December 2007. The present study compared the 3-year overall survival of two treatments (adjuvant CRT according to the INT 0116 trial versus resection alone). Survival curves were estimated by the Kaplan-Meier method and compared with a log-rank test. Multivariate analysis of prognostic factors was performed by the Cox proportional hazards model. RESULTS: A total of 185 patients were included, 104 patients (56 %) received adjuvant CRT and 81 received resection alone. The 3-year overall survival was 64.4 % in the CRT group and 61.7 % in the resection-alone group (p: 0.415). However, according to the Cox proportional hazards model, adjuvant CRT was a prognostic factor for 3-year overall survival (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.26-0.82, p: 0.008). CONCLUSIONS: In the present study, adjuvant CRT was associated with a lower risk of death over a 3-year period in gastric cancer patients treated with D2 lymphadenectomy.
Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/therapy , Chemoradiotherapy, Adjuvant/methods , Lymph Node Excision/methods , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant/mortality , Female , Follow-Up Studies , Gastrectomy/methods , Gastrectomy/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
Os autores analisam 19 casos de neoplasia maligna da papila de Vater registrados no Hospital A. C. Camargo, Säo Paulo, no período de 1953 a 1985. Esta neoplasia representou 0,29% dos tumores do aparelho digestivo registrados nesse período. Os sinais e sintomas mais importantes foram icterícia (94%) e hepatomegalia (75%). O tamanho médio dos tumores foi de 2,4cm. Dezesseis pacientes foram submetidos à cirurgia de Whipple, dois à derivaçäo biliar interna e um à papilotomia endoscópica e radioterapia. A mortalidade pós-operatória para os pacientes submetidos à cirurgia de Whipple foi de 25% e a sobrevida a cinco anos foi de 25%
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Ampulla of Vater , Common Bile Duct Neoplasms , Common Bile Duct Neoplasms/surgery , MethodsABSTRACT
Os autores, analisam a sobrevida de 452 pacientes portadores de adenocarcinoma gástrico matriculados no Departamento de Cirurgia Abdominal do Hospital A.C. Camargo e operados com finalidade radical. Os resultados säo apresentados de acordo com o estádio clínico e o número de linfonodos contaminados, verificando-se que os resultados declinam do EC I para o EC III e também com o número de linfonodos contaminados. Fazem também estudo comparativo dos resultados de tratamento em dois períodos: 1953 e 1970-1980, demonstrando melhora nos índices de sobrevida no segundo período
Subject(s)
Humans , Neoplasm Staging , Lymph Nodes/analysis , Stomach Neoplasms/surgeryABSTRACT
Relatam-se aspectos diagnósticos e terapêuticos de um caso de ruptura de baço em um paciente com linfoma, onde a dificuldade esteve em saber se a ruptura pós-trauma deveu-se a um órgäo infiltrado por linfoma ou näo, mostrando a importância da laparoscopia como método de estadiamento e indicadora do tratamento efetuado
