Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas.

OBJECTIVE: To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity. DESIGN: We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial. RESULTS: We found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-ß may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded CXCL13 + tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens. CONCLUSION: We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.

Clinical outcomes of patients with pancreatic tumors discussed in Tumor Board.

OBJECTIVE: the recommendations of the decisions made by the Tumor Board (TB) should be followed to identify barriers that may interfere with the execution of the previously decided, best care for the patient. The aim of this study is to assess whether the TB conduct decision was performed in patients with pancreatic tumors, their life status 90 days after the TB decision, and to analyze the reasons why the conduct was not performed. METHODS: we conducted a retrospective study with patients with pancreas tumors, evaluated between 2017 and 2019. We collected data on epidemiological status, whether the TB procedure was performed, the reason for not performing it, life status 90 days after the TB decision, and how many times each patient was discussed at a meeting. We compared categorical variables using the chi square test, numerical variables were presented as means and standard deviation. RESULTS: we studied 111 session cases, in 95 patients, 86 (90.5%) diagnosed with cancer. After 90 days of TB, 83 patients (87.37%) remained alive, 9 had (9.47%) died, and 3 (3.16%) were lost to follow-up. The TB decision was not observed in 12 (10.8%) cases and the reasons were: 25% (3) for loss of follow-up, 8.33% (1) for patient refusal, and 66.67% (8) due to clinical worsening. The cases of patients with metastases had a lower rate of TB conduct compliance (p=0.006). CONCLUSIONS: the TB conduct was performed in most cases and the most evident reason for non-compliance with the conducts is the patient's clinical worsening.

Evaluation of prognostic factors in patients undergoing first-line chemotherapy for advanced biliary tract cancer: a retrospective analysis from a South American cancer centre.

INTRODUCTION: Biliary tract cancers (BTCs) are rare tumours with regional differences. Prognostic factors are poorly understood. Gemcitabine + platinum (GP) is the standard first-line chemotherapy in metastatic patients. We aimed to search for prognostic factors in patients with advanced disease in a cancer centre in South America. METHODS: We conducted a retrospective analysis of patients with advanced BTC treated with chemotherapy. Variables were age (< or ≥70 years), Eastern Cooperative Oncology Group (ECOG) performance status (0/1 versus 2/3), gender, primary site (intrahepatic (IHC), extrahepatic (EHC), gallbladder (GB)), staging (locally advanced versus metastatic), metastatic sites, albumin (>3.5 g/dL versus <3.5 g/dL), biliary obstruction and first-line chemotherapy (GP, 5FU-based or single-agent). Cox regression method was used to explore factors. RESULTS: From 2010 to 2017, 104 patients were included. Median age was 62 years (32-86) and 22.1% were older than 70 years. Most patients had ECOG performance status 0/1 (63.4%), were female (51.9%) and were metastatic (82.7%). Bone metastases were found in 19.2%. Primary IHC, EHC and GB were 54.8%, 36.5% and 8.7%, respectively. GP was used by 79.8%. Median follow-up was 32.4 months. Median overall survival (mOS) was 11.4 months. In univariate analysis, male (p = 0.007), albumin < 3.5 g/dL (p = 0.001), biliary obstruction (p = 0.006), 5FU-based (p = 0.006) and single-agent (p < 0.0001) were associated with worse OS. ECOG performance status 2/3 (p = 0.058) and bone metastases (p = 0.051) were marginally related. In multivariate analysis, male (p = 0.003), bone metastases (p = 0.023), biliary obstruction (p = 0.001), 5FU-based (p = 0.016) and single-agent (p = 0.023) were independently associated with inferior OS. CONCLUSION: In this retrospective study, we observed that male patients, bone metastases, biliary obstruction and regimens other than GP had worse survival. Larger studies should be conducted to confirm our findings.

Allium vegetables intake and the risk of gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

ENDOSCOPIC CHARACTERISTICS OF PATIENTS WITH COMPLETE PATHOLOGICAL RESPONSE AFTER NEOADJUVANT CHEMOTHERAPY FOR GASTRIC AND ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMAS.

BACKGROUND: Gastric and esophagogastric junction adenocarcinoma are responsible for approximately 13.5% of cancer-related deaths. Given the fact that these tumors are not typically detected until they are already in the advanced stages, neoadjuvancy plays a fundamental role in improving long-term survival. Identification of those with complete pathological response (pCR) after neoadjuvant chemotherapy (NAC) is a major challenge, with effects on organ preservation, extent of resection, and additional surgery. There is little or no information in the literature about which endoscopic signs should be evaluated after NAC, or even when such re-evaluation should occur. AIM: To describe the endoscopic aspects of patients with gastric and esophagogastric junction adenocarcinomas who underwent NAC and achieved pCR, and to determine the accuracy of esophagogastroduodenoscopy (EGD) in predicting the pCR. METHODS: A survey was conducted of the medical records of patients with these tumors who were submitted to gastrectomy after NAC, with anatomopathological result of pCR. RESULTS: Twenty-nine patients were identified who achieved pCR after NAC within the study period. Endoscopic responses were used to classify patients into two groups: G1-endoscopic findings consistent with pCR and G2-endoscopic findings not consistent with pCR. Endoscopic evaluation in G1 was present in an equal percentage (47.4%; p=0.28) in Borrmann classification II and III. In this group, the predominance was in the gastric body (57.9%; p=0.14), intestinal subtype with 42.1% (p=0.75), undifferentiated degree, 62.5% (p=0.78), Herb+ in 73.3% (p=0.68). The most significant finding, however, was that the time interval between NAC and EGD was longer for G1 than G2 (24.4 vs. 10.2 days, p=0.008). CONCLUSION: EGD after NAC seems to be a useful tool for predicting pCR, and it may be possible to use it to create a reliable response classification. In addition, the time interval between NAC and EGD appears to significantly influence the predictive power of endoscopy for pCR.

Clinical outcomes of patients with pancreatic tumors discussed in Tumor Board / Desfechos clínicos dos pacientes com tumores de pâncreas discutidos em Tumor Board

ABSTRACT Objective: the recommendations of the decisions made by the Tumor Board (TB) should be followed to identify barriers that may interfere with the execution of the previously decided, best care for the patient. The aim of this study is to assess whether the TB conduct decision was performed in patients with pancreatic tumors, their life status 90 days after the TB decision, and to analyze the reasons why the conduct was not performed. Methods: we conducted a retrospective study with patients with pancreas tumors, evaluated between 2017 and 2019. We collected data on epidemiological status, whether the TB procedure was performed, the reason for not performing it, life status 90 days after the TB decision, and how many times each patient was discussed at a meeting. We compared categorical variables using the chi square test, numerical variables were presented as means and standard deviation. Results: we studied 111 session cases, in 95 patients, 86 (90.5%) diagnosed with cancer. After 90 days of TB, 83 patients (87.37%) remained alive, 9 had (9.47%) died, and 3 (3.16%) were lost to follow-up. The TB decision was not observed in 12 (10.8%) cases and the reasons were: 25% (3) for loss of follow-up, 8.33% (1) for patient refusal, and 66.67% (8) due to clinical worsening. The cases of patients with metastases had a lower rate of TB conduct compliance (p=0.006). Conclusions: the TB conduct was performed in most cases and the most evident reason for non-compliance with the conducts is the patient's clinical worsening.

RESUMO Objetivo: as recomendações das decisões em Tumor Board (TB) deveriam ser acompanhadas para identificar barreiras que possam interferir na execução do melhor cuidado para o paciente decidido previamente. O objetivo do estudo é avaliar se a decisão de conduta em TB foi realizada em pacientes com tumores pancreáticos, o status de vida 90 dias após TB e analisar os motivos pelos quais a conduta não foi realizada. Métodos: estudo retrospectivo com pacientes com tumores de pâncreas, avaliados entre 2017 a 2019. Dados epidemiológicos, se a conduta de TB foi realizada, o motivo da não realização, o status de vida em 90 dias após decisão de TB e quantas vezes cada paciente foi discutido em reunião foram coletados. As variáveis categóricas foram comparadas pelo teste de qui-quadrado; variáveis numéricas foram apresentadas como médias e desvio padrão. Resultados: 111 casos, 95 pacientes, 86 (90,5%) com diagnóstico de câncer. Após 90 dias de TB, 83 pacientes (87,37%) permaneceram vivos, 9 pacientes (9,47%) faleceram e 3 (3,16%) perderam o seguimento. A conduta do TB não foi realizada em 12 (10,8%) dos casos e os motivos foram: 25% (3) por perda de seguimento, 8,33% (1) por recusa do paciente e 66,67% (8) devido à piora clínica. Os casos de pacientes com metástases tiveram menor execução de conduta de TB (p=0,006). Conclusões: a conduta do TB é realizada na maior parte dos casos e o motivo mais evidente para o não cumprimento das condutas é a piora clínica do paciente.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

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.

Disparities in access to health care system as determinant of survival for patients with pancreatic cancer in the State of São Paulo, Brazil.

Little is known about the features and outcomes of Brazilian patients with pancreatic cancer. We sought to describe the socio-economic characteristics, patterns of health care access, and survival of patients diagnosed with malignant pancreatic tumors from 2000 to 2014 in São Paulo, Brazil. We included patients with malignant exocrine and non-classified pancreatic tumors according to the International Classifications of Disease (ICD)-O-2 and -O-3, diagnosed from 2000 to 2014, who were registered in the FOSP database. Prognostic factors for overall survival (OS) in the subgroup of patients with ductal or non-specified (adeno)carcinoma were evaluated using Cox proportional hazard model. The study population consists of 6855 patients. Median time from the first visit to diagnosis and treatment were 13 (Interquartile range [IQR] 4-30) and 24 (IQR 8-55) days, respectively. Both intervals were longer for patients treated in the public setting. Median OS was 4.9 months (95% confidence interval [95% CI] 4.7-5.2). Increasing age, male gender, lower educational level, treatment in the public setting, absence of treatment, advanced stage, and treatment from 2000 to 2004 were associated with inferior OS. From 2000-2004 to 2010-2014, no improvement in OS was seen for patients treated in the public setting. Survival of patients with malignant pancreatic tumors remains dismal. Socioeconomical variables, especially health care funding, are major determinants of survival. Further work is necessary to decrease inequalities in access to medical care for patients with pancreatic cancer in Brazil.

Informed consent and a risk-based approach to oncologic surgery in a cancer center during the COVID-19 pandemic.

BACKGROUND: Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). OBJECTIVES: To report an IC and an algorithm developed for oncologic surgery during the COVID-19 outbreak. METHODS: We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS-CoV-2 test and described all perioperative steps of this program. RESULTS: Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS-CoV-2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. CONCLUSIONS: During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.

Endoscopic characteristics of patients with complete pathological response after neoadjuvant chemotherapy for gastric and esophagogastric junction adenocarcinomas / Características endoscópicas de pacientes com resposta patológica completa após quimioterapia neoadjuvante para adenocarcinomas gástricos e de junção esofagogástrica

ABSTRACT Background: Gastric and esophagogastric junction adenocarcinoma are responsible for approximately 13.5% of cancer-related deaths. Given the fact that these tumors are not typically detected until they are already in the advanced stages, neoadjuvancy plays a fundamental role in improving long-term survival. Identification of those with complete pathological response (pCR) after neoadjuvant chemotherapy (NAC) is a major challenge, with effects on organ preservation, extent of resection, and additional surgery. There is little or no information in the literature about which endoscopic signs should be evaluated after NAC, or even when such re-evaluation should occur. Aim: To describe the endoscopic aspects of patients with gastric and esophagogastric junction adenocarcinomas who underwent NAC and achieved pCR, and to determine the accuracy of esophagogastroduodenoscopy (EGD) in predicting the pCR. Methods: A survey was conducted of the medical records of patients with these tumors who were submitted to gastrectomy after NAC, with anatomopathological result of pCR. Results: Twenty-nine patients were identified who achieved pCR after NAC within the study period. Endoscopic responses were used to classify patients into two groups: G1-endoscopic findings consistent with pCR and G2-endoscopic findings not consistent with pCR. Endoscopic evaluation in G1 was present in an equal percentage (47.4%; p=0.28) in Borrmann classification II and III. In this group, the predominance was in the gastric body (57.9%; p=0.14), intestinal subtype with 42.1% (p=0.75), undifferentiated degree, 62.5% (p=0.78), Herb+ in 73.3% (p=0.68). The most significant finding, however, was that the time interval between NAC and EGD was longer for G1 than G2 (24.4 vs. 10.2 days, p=0.008). Conclusion: EGD after NAC seems to be a useful tool for predicting pCR, and it may be possible to use it to create a reliable response classification. In addition, the time interval between NAC and EGD appears to significantly influence the predictive power of endoscopy for pCR.

RESUMO Racional: O adenocarcinoma gástrico e da junção esofagogástrica é responsável por aproximadamente 13,5% das mortes relacionadas ao câncer. Dado que esses tumores não são normalmente detectados até que já estejam em estágios avançados, a neoadjuvância desempenha um papel fundamental na melhoria da sobrevida em longo prazo. A identificação daqueles com resposta patológica completa (pCR) após a quimioterapia neoadjuvante (NAC) é um grande desafio, com efeitos na preservação do órgão, extensão da ressecção e cirurgia adicional. Há pouca ou nenhuma informação na literatura sobre quais sinais endoscópicos devem ser avaliados após a NAC, ou mesmo quando essa reavaliação deve ocorrer. Objetivo: Descrever os aspectos endoscópicos de pacientes com adenocarcinoma gástrico e da junção esofagogástrica que foram submetidos à quimioterapia neoadjuvante e alcançaram pCR, e determinar a acurácia da esofagogastroduodenoscopia (EGD) em predizer a pCR. Métodos: Foram revisados os prontuários de pacientes submetidos à gastrectomia subtotal e total após NAC, com resultado anatomopatológico de pCR. Resultados: Vinte e nove pacientes que alcançaram pCR após NAC foram identificados no período estudado. As respostas endoscópicas foram usadas para classificar os pacientes em dois grupos: G1- achados endoscópicos consistentes com pCR, G2 - achados endoscópicos não consistentes com pCR. A avaliação endoscópica no G1 esteve presente em igual percentual (47,4%; p=0,28) na classificação de Borrmann II e III. Nesse grupo, a predominância foi no corpo gástrico (57,9%; p=0,14), subtipo intestinal com 42,1% (p=0,75), grau indiferenciado, 62,5% (p=0,78), Herb+ em 73,3% (p=0,68). O achado mais significativo, no entanto, foi que o intervalo de tempo entre NAC e EGD foi maior para G1 do que G2 (24,4 vs. 10,2 dias, p=0,008). Conclusão: A EGD após NAC, nessa pesquisa, sugeriu ser método útil para prever pCR, mediante uma classificação de resposta confiável. Além disso, o intervalo de tempo entre NAC e EGD parece influenciar significativamente a sua capacidade preditiva de diagnosticar a pCR.

Brazilian gastric cancer association guidelines (part 2): update on treatment / Diretrizes da associação brasileira de câncer gástrico (parte 2): atualização sobre o tratamento

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.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

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.

The diffuse-type gastric cancer epidemiology enigma.

BACKGROUND: Intestinal and diffuse gastric adenocarcinomas differ in clinical, epidemiological and molecular features. However, most of the concepts related to the intestinal-type are translated to gastric adenocarcinoma in general; thus, the peculiarities of the diffuse-type are underappreciated. RESULTS: Besides its growing importance, there are many gaps about the diffuse-type carcinogenesis and, as a result, its epidemiologic and pathogenetic features remain poorly understood. CONCLUSIONS: Alternative hypotheses to explain these features are discussed, including the role of the gastric microbiota, medical therapies, and modifications in the stomach's microenvironment.

Does hipec improve outcomes in gastric cancer patients treated with perioperative chemotherapy and radical surgery? A propensity-score matched analysis.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with improved survival when compared with surgery alone for non-metastatic gastric cancer patients in randomized trials and meta-analyses. However, little evidence is available regarding the use of HIPEC in nonmetastatic patients who are treated with perioperative chemotherapy and radical surgery. The aim of this study was to investigate the putative survival benefit of HIPEC in the subgroup of gastric cancer patients treated with perioperative chemotherapy and surgery. PATIENTS AND METHODS: This was a retrospective cohort study that included gastroesophageal junction and gastric cancer patients who were treated with perioperative chemotherapy and curative resection in a single cancer center in the period between 2006 and 2017. In this time period, younger patients with diffuse-type tumors and serosa invasion or positive lymph node disease were often offered an adjuvant HIPEC protocol. This study compared the survival outcomes of these patients to the ones of those who received only perioperative chemotherapy and resection. A 2:1 propensity-score matched analysis for the two groups was also performed, and variables used were postchemotherapy T (ypT) and N (ypN) stages, histology and tumor site. RESULTS: The study population comprised 269 subjects, 241 treated with chemotherapy and surgery and 28 who also received HIPEC. The mean age was 59 years old (standard deviation: 12.2) and 60% of all individuals were male. A total gastrectomy was performed in 137 patients and a distal resection in 132, with a D2-lymphadenectomy in 97.4% of the sample. Overall 60-day morbidity and mortality rates were 35.3% and 3.3%, respectively. In the HIPEC group, patients were younger, and more frequently had American Society of Anesthesiologists (ASA) 1 to 2 classification, tumors located in the gastric body, had diffuse histology, and ypN+ disease. Overall survival (OS; 5 years) results in the HIPEC and no HIPEC group were 59.5% vs 68.7% (P = .453), and disease-free survival (DFS) ones were 49.5% and 65.8% (P = .060), respectively. In the multivariable Cox regression model, ypT and ypN were independent overall and DFS predictors; also, ASA 3 to 4 classification and diffuse histology were associated with worse OS. In the matched analysis, HIPEC did not improve either overall (53.5% vs 59.5%; P = .517) or DFS (50.0% vs 49.5%; P = .993). CONCLUSION: Treatment with HIPEC in patients who received perioperative chemotherapy and a D2-resection did not improve survival outcomes. Both ypT and ypN stages remained as the most important survival predictors in this cohort.

Ii brazilian consensus on gastric cancer by the brazilian gastric cancer association / Ii consenso brasileiro de câncer gástrico realizado pela associação brasileira de câncer gástrico

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.

Padrão de resposta patológica à quimioterapia neoadjuvante em câncer gástrico: relação com fatores prognósticos e sobrevida / Pathologic response profile to neoadjuvant chemotherapy in gastric cancer: relationship with prognostic factors and survival

Introdução: A quimioterapia perioperatória e cirurgia são o padrão de tratamento para pacientes com câncer gastroesofágico avançado, entretanto, seu impacto entre aqueles tratados com cirurgia radical carece de avaliação mais detalhada. Apresentamos os resultados desta abordagem de tratamento multimodal em uma coorte de pacientes com câncer gástrico tratados com linfadenectomia D2. Objetivo: identificar fatores prognósticos associados à melhora da sobrevida e resposta patológica associados ao tratamento neoadjuvante. Pacientes e métodos. Este estudo de coorte retrospectivo envolveu pacientes tratados com quimioterapia perioperatória e ressecção em um único centro oncológico no Brasil entre 2006 e 2016. Indivíduos com tumores do coto gástrico, tumores de esôfago ou tratados com quimioterapia intra-peritoneal foram excluídos. A análise de sobrevivência com intenção de tratar foi realizada para todos os indivíduos que iniciaram a quimioterapia neoadjuvante, e os fatores prognósticos foram determinados entre aqueles que tiveram ressecção R0. Resultados. Este estudo incluiu 239 pacientes, dos quais 198 tiveram ressecção R0. A média de idade foi de 59,9 anos e a maioria apresentava doença em estágio clínico IIB ou III (88%). Entre os 239 pacientes que iniciaram quimioterapia neoadjuvante, 207 (86,6%) completaram todos os ciclos de tratamento neoadjuvante, e a ressecção cirúrgica foi realizada em 225 indivíduos (94,1%). As taxas gerais de morbidade e mortalidade em 60 dias foram de 35,6% e 4,4%, respectivamente. Para toda a coorte, a sobrevida mediana foi de 78 meses e a taxa de sobrevida em 5 anos foi de 55,3%. Os fatores associados à pior sobrevida foram estágio ypT3­4, ypN, estágio, ressecção estendida e sem quimioterapia adjuvante. Conclusões. A quimioterapia perioperatória resultou em resultados muito bons para pacientes tratados com cirurgia radical, e o downstaging após a quimioterapia mostrou ser um determinante principal do prognóstico

Background. Perioperative chemotherapy and surgery are the standard of care in advanced gastroesophageal cancer patients, but its impact among those treated with radical surgery still needs further assessment. We present the results of this multimodality treatment approach in a gastric cancer patients cohort treated with D2 lymphadenectomy. We aimed to identify prognostic factors associated with improved survival. Patients and Methods. This retrospective cohort study enrolled patients treated with perioperative chemotherapy and resection in a single cancer center in Brazil between 2006 and 2016. Subjects presenting tumors of the gastric stump, esophageal tumors, or treated with intraperitoneal chemotherapy were excluded. Intention-to-treat survival analysis was performed for all subjects who started neoadjuvant chemotherapy, and prognostic factors were determined among those who had R0 resection. Results. This study included 239 patients, of whom 198 had R0 resection. The mean age was 59.9 years, and most had clinical stage IIB or III disease (88%). Among the 239 patients who started neoadjuvant chemotherapy, 207 (86.6%) completed all neoadjuvant treatment cycles, and surgical resection was performed in 225 subjects (94.1%). Overall 60-day morbidity and mortality rates were 35.6% and 4.4%, respectively. For the entire cohort, median survival was 78 months and the 5-year survival rate was 55.3%. Factors associated with worse survival were ypT3­4 stage, ypN stage, extended resection, and no adjuvant chemotherapy. Conclusions. Perioperative chemotherapy resulted in very good outcomes for patients treated with radical surgery, and downstaging after chemotherapy was shown to be a major determinant of prognosis

Computed tomography-measured body composition: correlation with postoperative morbidity and mortality in patients with gastroesophageal cancer / Correlação entre a composição corporal medida pela tomografia computadorizada e a morbimortalidade pós-operatória em pacientes com câncer gastroesofágico

Abstract Objective: To determine whether preoperative anthropometric and computed tomography (CT) measurements of body composition can predict postoperative morbidity and mortality in patients with gastric or esophageal cancer. Materials and Methods: This was a retrospective study in which we reviewed the medical records and abdominal CT scans of patients with gastric or esophageal cancer who underwent surgery in 2015 at a cancer center. CT scans performed during routine preoperative evaluation were retrospectively assessed to measure the area of lean body mass at the level of the third lumbar vertebra, as well as the area of visceral and subcutaneous fat. Results: Seventy patients were included in the study. The mean age was 59.9 years (range, 33-82 years), and 47 patients (67.1%) were men. The mean postoperative follow-up period was 14.9 months. Neither postoperative morbidity nor postoperative mortality correlated significantly with gender, age, the type of primary tumor, the presence of comorbidities, smoking status, body mass index, nutritional status, or visceral fat area. The survival rate was higher for patients with normal lean body mass than for those with low lean body mass (hazard ratio = 0.116; 95% confidence interval: 0.015-0.906; p = 0.040). Conclusion: Our data suggest that lean body mass can be a relevant prognostic factor in patients with gastric or esophageal cancer, and that CT measurements should be included in the routine preoperative evaluation, because it may provide information that aids nutritional and clinical care for these patients.

Resumo Objetivo: Investigar se medidas antropométricas e tomografia computadorizada (TC) da composição corporal podem predizer morbimortalidade pós-operatória em pacientes com câncer gástrico e/ou esofágico. Materiais e Métodos: Estudo retrospectivo que revisou prontuários médicos e TCs abdominais de pacientes com câncer gástrico e/ou esofágico que foram operados em 2015 em um centro de referência oncológico. As TCs realizadas durante a avaliação pré- operatória de rotina foram avaliadas retrospectivamente para medir a área de massa magra ao nível de L3 e gordura visceral e subcutânea. Resultados: Setenta pacientes foram incluídos no estudo. A média de idade foi 59,9 anos (faixa de 33-82 anos), e 47 desses pacientes (67,1%) eram homens. O seguimento pós-operatório médio foi 14,9 meses. Não houve associação significativa entre morbidade ou mortalidade pós-operatória e sexo, idade, tumor primário, comorbidades, tabagismo, índice de massa corpórea, diagnóstico nutricional ou área de gordura visceral. A taxa de sobrevida foi maior para pacientes com área de massa magra normal, em comparação com pacientes com baixa área de massa magra (hazard ratio = 0,116; intervalo de confiança 95% = 0,015-0,906; p = 0,040). Conclusão: Nossos dados sugerem que a área de massa magra pode ser um importante fator prognóstico em pacientes com câncer gástrico e/ou esofágico, e sua medida na TC deve ser incluída na avaliação pré-operatória de rotina, podendo fornecer informações que auxiliem no manejo clínico e nutricional desses pacientes.