Prognostic implications of tumor-infiltrating lymphocytes within the tumor microenvironment in gastric cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) play a regulatory role in the tumor-associated immune response and are important in the prognosis and treatment response of several cancers. However, because of its heterogeneity, the prognostic value of TILs in gastric cancer (GC) is still controversial. Thus, this study aimed to investigate the association between the density of TILs and patients' outcomes in GC. METHODS: Patients with gastric adenocarcinoma who underwent curative intent gastrectomy were retrospectively investigated. The groups for analysis were determined on the basis of TIL intensity and percentage of CD3+ T-cell infiltration by immunohistochemical. Furthermore, Epstein-Barr virus (EBV), microsatellite instability (MSI), T-cell ratio of CD4 to CD8, and programmed death protein ligand 1 (PD-L1) status were evaluated. RESULTS: A total of 345 patients were enrolled: 124 patients with GCs (35.9%) were classified as the low-CD3+ TIL group, and 221 patients with GCs (64.1%) were classified as the high-CD3+ TIL group. Poorly differentiated histology (P = .014), EBV-positive status (P < .001), PD-L1-positive status (P = .001), and CD4 < CD8 (P < .001) were associated with high-CD3+ GC. There was no difference regarding MSI status, the degree of tumor invasion (pT), the presence of lymph node metastasis, and pTNM stage between low- and high-CD3+ groups. In survival analysis, the high-CD3+ group had better disease-free survival and overall survival rates than had the low-CD3+ group (P = .055 and P = .041, respectively). In the multivariate analysis, total gastrectomy, lymph node metastasis, advanced pT stage, and low CD3+ levels were independent factors related to worse survival. CONCLUSION: High CD3+ TILs levels were significantly associated with improved survival and could serve as prognostic biomarkers in GC. In addition, CD3+ T-cell infiltration was related to both EBV-positive and PD-L1-positive GC and may assist in the investigation of targets in immunotherapy.

Thawed Porcine Model for Surgical Training: A Novel Conservative Procedure.

Background: General Surgery course is a mandatory in medical schools and continuing surgery training is important even to experienced surgeons which they need to maintain and/or improve their surgical skills. Additionally, the models used for that practice are human cadavers, anesthetized porcine, or simulators and are not accessible for medicine schools or physicians in many countries. Therefore, we present a new technical procedure for preparation of frozen experimental animal's cadavers for medical surgical training. Materials and Methods: To perform the study, one porcine slaughtered and frozen at -20°C was used. The porcine cadaver was thawed at room temperature (25°C) and then the pneumoperitoneum test was performed and viscera inspection carried out. Results: The porcine cadaver took 20 hours to completely thaw. The pneumoperitoneum was successfully performed with total distention of the abdominal cavity. All viscera were well preserved maintaining important in vivo characteristics for consistency. Conclusion: The use of thawed porcine cadaver as a model to train many surgical procedures including videolaparoscopy is feasible. The tissues were well preserved by this method and was financially accessible and could be used for different techniques, equipment, and material tests.

Efficacy and Safety of Sleeve Gastrectomy with Jejunoileal Bypass Compared with Roux-en-Y Gastric Bypass: Results from a Cohort Study.

Background: We previously described sleeve gastrectomy with jejunoileal bypass (SGJIB) as promising novel technique for the surgical treatment of obesity Methods: A retrospective analysis of a prospective database in a Private Practice of Alimentary Tract Surgery in São Paulo, Brazil. We analyzed 176 patients with 60 months of follow-up, 74 of whom underwent Vertical Sleeve Gastrectomy with Jejunoileal Bypass (VSG-JIB) (50 women and 24 men) with a mean age of 38 years and a mean body mass index (BMI) of 40 kg/m2, and 102 patients underwent Roux-en-Y gastric bypass (RYGB) (90 women and 12 men) with a mean age of 36.5 years and a mean BMI of 39.73 kg/m2. Results: There was no statistically significant difference in long-term weight loss between the two groups. The rate of postoperative complications immediately after surgery was similar, but there was a tendency toward less severe complications in the SGJIB cohort. Conclusion: Sleeve gastrectomy with jejunoileal bypass is a novel surgical procedure for weight loss with comparable efficacy and safety compared with laparoscopic RYGB.

Weight and Glucose Control in Rats Submitted to Sleeve Gastrectomy with Cafeteria Diet-Induced Obesity.

Introduction: Sleeve gastrectomy (SG) has been widely disseminated as a surgical treatment for obesity and associated comorbidities, and currently it is one of the most performed surgeries in the world. Experimental research is becoming increasingly relevant to characterize the pathophysiological mechanisms induced by it. Objective: The aim of this study was to standardize an experimental model of SG in rats with obesity induced using a cafeteria diet (CAF) and evaluate variations in weight and glycemic control after vertical SG, maintaining the CAF. Materials and Methods: Twenty Rattus norvegicus albinus rats, Wistar strain, with an average weight of 250 g were used. The animals were randomized into two groups and underwent 4 weeks of obesity induction before the procedure. In 10 animals of the SG group, vertical SG was performed, and in 10 animals of the control/sham (C) group, simulated surgery was performed, consisting of laparotomy and bidigital compression of the stomach. The animals were followed for a total of 8 weeks, with the weight assessed weekly and fasting blood glucose assessed before the start of the CAF, at the time of surgery, and after 4 weeks of the postoperative period, when they were sacrificed. Results: Before obesity induction, the average weight was 257.8 g in the SG group 266.1 g in the C group. After obesity induction, the average weight was 384 g in the vertical sleeve gastrectomy group and 374.8 g in the C group. In the fourth postoperative week, the average weight was 391.6 g in the VSG group and 436.6 g in the C group. The average blood glucose levels were 88.7, 101.8, and 91.3 mg/dL in the VSG group and 86.6, 103.1, and 109.4 mg/dL in the C group, respectively, before the start of the diet, in the fourth preoperative week, and in the fourth postoperative week. Conclusions: Vertical SG in rats is feasible and promotes glycemic control in the postoperative period. CAF allows induction of obesity and changes in blood glucose.

Preoperative albumin-bilirubin score is a prognostic factor for gastric cancer patients after curative gastrectomy.

BACKGROUND: Albumin-bilirubin (ALBI) score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular carcinomas. Currently, this liver function index has been used to predict prognosis in other neoplasms. However, the significance of ALBI score in gastric cancer (GC) after radical resection has not been elucidated. AIM: To evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative treatment. METHODS: Patients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective database. ALBI score was calculated as follows: (log10 bilirubin × 0.660) + (albumin × -0.085). The receiver operating characteristic curve with area under the curve (AUC) was plotted to evaluate the ability of ALBI score in predicting recurrence or death. The optimal cutoff value was determined by maximizing Youden's index, and patients were divided into low and high-ALBI groups. The Kaplan-Meier curve was used to analyze the survival, and the log-rank test was used for comparison between groups. RESULTS: A total of 361 patients (235 males) were enrolled. The median ALBI value for the entire cohort was -2.89 (IQR -3.13; -2.59). The AUC for ALBI score was 0.617 (95%CI: 0.556-0.673, P < 0.001), and the cutoff value was -2.82. Accordingly, 211 (58.4%) patients were classified as low-ALBI group and 150 (41.6%) as high-ALBI group. Older age (P = 0.005), lower hemoglobin level (P < 0.001), American Society of Anesthesiologists classification III/IV (P = 0.001), and D1 lymphadenectomy P = 0.003) were more frequent in the high-ALBI group. There was no difference between both groups in terms of Lauren histological type, depth of tumor invasion (pT), presence of lymph node metastasis (pN), and pathologic (pTNM) stage. Major postoperative complication, and mortality at 30 and 90 days were higher in the high-ALBI patients. In the survival analysis, the high-ALBI group had worse disease-free survival (DFS) and overall survival (OS) compared to those with low-ALBI (P < 0.001). When stratified by pTNM, the difference between ALBI groups was maintained in stage I/II and stage III CG for DFS (P < 0.001 and P = 0.021, respectively); and for OS (P < 0.001 and P = 0.063, respectively). In multivariate analysis, total gastrectomy, advanced pT stage, presence of lymph node metastasis and high-ALBI were independent factors associated with worse survival. CONCLUSION: The preoperative ALBI score is able to predict the outcomes of patients with GC, where high-ALBI patients have worse prognosis. Also, ALBI score allows risk stratification of patients within the same pTNM stages, and represents an independent risk factor associated with survival.

PREOPERATIVE CHEMOTHERAPY VERSUS UPFRONT SURGERY FOR ADVANCED GASTRIC CANCER: A PROPENSITY SCORE MATCHING ANALYSIS.

BACKGROUND: Surgical resection remains the main curative therapeutic modality for advanced gastric cancer. Recently, the association of preoperative chemotherapy has allowed the improvement of results without increasing surgical complications. AIMS: To evaluate the surgical and oncological outcomes of preoperative chemotherapy in a real-world setting. METHODS: A retrospective review of gastric cancer patients who underwent gastrectomy was performed. Patients were divided into two groups for analysis: upfront surgery and preoperative chemotherapy. The propensity score matching analysis, including 9 variables, was applied to adjust for potential confounding factors. RESULTS: Of the 536 patients included, 112 (20.9%) were referred for preoperative chemotherapy. Before the propensity score matching analysis, the groups were different in terms of age, hemoglobin level, node metastasis at clinical stage- status, and extent of gastrectomy. After the analysis, 112 patients were stratified for each group. Both were similar for all variables assigned in the score. Patients in the preoperative chemotherapy group had less advanced postoperative p staging (p=0.010), postoperative n staging (p<0.001), and pTNM stage (p<0.001). Postoperative complications, 30- and 90-days mortality were similar between both groups. Before the propensity score matching analysis, there was no difference in survival between the groups. After the analysis, patients in the preoperative chemotherapy group had better overall survival compared to upfront surgery group (p=0.012). Multivariate analyses demonstrated that American Society of Anesthesiologists III/IV category and the presence of lymph node metastasis were factors significantly associated with worse overall survival. CONCLUSIONS: Preoperative chemotherapy was associated with increased survival in gastric cancer. There was no difference in the postoperative complication rate and mortality compared to upfront surgery.

INTRAPERITONEAL CHEMOTHERAPY FOR GASTRIC CANCER WITH PERITONEAL CARCINOMATOSIS: STUDY PROTOCOL OF A PHASE II TRIAL.

BACKGROUND: Peritoneal carcinomatosis in gastric cancer is considered a fatal disease, without expectation of definitive cure. As systemic chemotherapy is not sufficient to contain the disease, a multimodal approach associating intraperitoneal chemotherapy with surgery may represent an alternative for these cases. AIMS: The aim of this study was to investigate the role of intraperitoneal chemotherapy in stage IV gastric cancer patients with peritoneal metastasis. METHODS: This study is a single institutional single-arm prospective clinical trial phase II (NCT05541146). Patients with the following inclusion criteria undergo implantation of a peritoneal catheter for intraperitoneal chemotherapy: Stage IV gastric adenocarcinoma; age 18-75 years; Peritoneal carcinomatosis with peritoneal cancer index<12; Eastern Cooperative Oncology Group 0/1; good clinical status; and lab exams within normal limits. The study protocol consists of four cycles of intraperitoneal chemotherapy with paclitaxel associated with systemic chemotherapy. After treatment, patients with peritoneal response assessed by staging laparoscopy undergo conversion gastrectomy. RESULTS: The primary outcome is the rate of complete peritoneal response. Progression-free and overall survivals are other outcomes evaluated. The study started in July 2022, and patients will be screened for inclusion until 30 are enrolled. CONCLUSIONS: Therapies for advanced gastric cancer patients have been evaluated in clinical trials but without success in patients with peritoneal metastasis. The treatment proposed in this trial can be promising, with easy catheter implantation and ambulatory intraperitoneal chemotherapy regime. Verifying the efficacy and safety of paclitaxel with systemic chemotherapy is an important progress that this study intends to investigate.

Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer.

BACKGROUND: Gastric cancer (GC) is still a prevalent neoplasm around the world and its main treatment modality is surgical resection. The need for perioperative blood transfusions is frequent, and there is a long-lasting debate regarding its impact on survival. AIM: To evaluate the factors related to the risk of receiving red blood cell (RBC) transfusion and its influence on surgical and survival outcomes of patients with GC. METHODS: Patients who underwent curative resection for primary gastric adenocarcinoma at our Institute between 2009 and 2021 were retrospectively evaluated. Clinicopathological and surgical characteristics data were collected. The patients were divided into transfusion and non-transfusion groups for analysis. RESULTS: A total of 718 patients were included, and 189 (26.3%) patients received perioperative RBC transfusion (23 intraoperatively, 133 postoperatively, and 33 in both periods). Patients in the RBC transfusions group were older (P < 0.001), and had more comorbidities (P = 0.014), American Society of Anesthesiologists classification III/IV (P < 0.001), and lower preoperative hemoglobin (P < 0.001) and albumin levels (P < 0.001). Larger tumors (P < 0.001) and advanced tumor node metastasis stage (P < 0.001) were also associated with the RBC transfusion group. The rates of postoperative complications (POC) and 30-d and 90-d mortality were significantly higher in the RBC transfusion group than in the non-transfusion group. Lower hemoglobin and albumin levels, total gastrectomy, open surgery, and the occurrence of POC were factors associated with the RBC transfusion. Survival analysis demonstrated that the RBC transfusions group had worse disease-free survival (DFS) and overall survival (OS) compared with patients who did not receive transfusion (P < 0.001 for both). In multivariate analysis, RBC transfusion, major POC, pT3/T4 category, pN+, D1 lymphadenectomy, and total gastrectomy were independent risk factors related to worse DFS and OS. CONCLUSION: Perioperative RBC transfusion is associated with worse clinical conditions and more advanced tumors. Further, it is an independent factor related to worse survival in the curative intent gastrectomy setting.

Gastroduodenal Perforation in Cancer Patients: Association with Chemotherapy and Prognosis.

BACKGROUND: Gastroduodenal perforation stands out as one of the complications in cancer patients. Despite its high mortality, its characteristics are still poorly described. This study aimed to evaluate the characteristics and outcomes of cancer patients who had gastroduodenal perforation, and the influence of chemotherapy (CMT) in these cases. METHOD: A retrospective analysis of patients who underwent emergency surgery with an intraoperative finding of gastroduodenal perforation. Patients who performed CMT within 60 days before perforation were considered as the CMT group. RESULTS: Among 45 patients included, 16 (35.5%) were classified as the CMT group and the remaining 29 (64.5%) patients as the non-CMT group. There was no difference between the groups regarding sex, age, BMI, comorbidity, and laboratory exams. ECOG 2-3 was significantly more frequent in the CMT group (68.8% vs. 34.5% p = 0.027). Major postoperative complications were similar between both groups (75% vs. 58.6%, p = 0.272). The sepsis of abdominal focus was the main postoperative complication. The 30-day mortality was 55.6%, with no difference between non-CMT and CMT groups (62.5% vs. 51.7%, respectively; p = 0.486). A multivariate analysis of risk factors showed that only an age of ≥65 years was related to 30-day mortality. CONCLUSIONS: Patients with gastroduodenal perforation and oncologic treatment present high mortality, regardless of receiving recent CMT.

STAGING LAPAROSCOPY IS STILL A VALUABLE TOOL FOR OPTIMAL GASTRIC CANCER MANAGEMENT.

BACKGROUND: Complete surgical resection is the main determining factor in the survival of advanced gastric cancer patients, but is not indicated in metastatic disease. The peritoneum is a common site of metastasis and preoperative imaging techniques still fail to detect it. AIM: The aim of this study was to evaluate the role of staging laparoscopy in the staging of advanced gastric cancer patients in a Western tertiary cancer center. METHODS: A total of 130 patients with gastric adenocarcinoma who underwent staging laparoscopy from 2009 to 2020 were evaluated from a prospective database. Clinicopathological characteristics were analyzed to identify factors associated with the presence of peritoneal metastasis and were also evaluated the accuracy and strength of agreement between computed tomography and staging laparoscopy in detecting peritoneal metastasis and the change in treatment strategy after the procedure. RESULTS: The peritoneal metastasis was identified in 66 (50.76%) patients. The sensitivity, specificity, and accuracy of computed tomography in detecting peritoneal metastasis were 51.5, 87.5, and 69.2%, respectively. According to the Kappa coefficient, the concordance between staging laparoscopy and computed tomography was 38.8%. In multivariate analysis, ascites (p=0.001) and suspected peritoneal metastasis on computed tomography (p=0.007) were statistically correlated with peritoneal metastasis. In 40 (30.8%) patients, staging and treatment plans changed after staging laparoscopy (32 patients avoided unnecessary laparotomy, and 8 patients, who were previously considered stage IVb by computed tomography, were referred to surgical treatment). CONCLUSION: The staging laparoscopy demonstrated an important role in the diagnosis of peritoneal metastasis, even with current advances in imaging techniques.

Preoperative chemotherapy versus upfront surgery for advanced gastric cancer: a propensity score matching analysis / Quimioterapia pré-operatória versus cirurgia de princípio para câncer gástrico avançado: análise por escore de propensão

ABSTRACT BACKGROUND: Surgical resection remains the main curative therapeutic modality for advanced gastric cancer. Recently, the association of preoperative chemotherapy has allowed the improvement of results without increasing surgical complications. AIMS: To evaluate the surgical and oncological outcomes of preoperative chemotherapy in a real-world setting. METHODS: A retrospective review of gastric cancer patients who underwent gastrectomy was performed. Patients were divided into two groups for analysis: upfront surgery and preoperative chemotherapy. The propensity score matching analysis, including 9 variables, was applied to adjust for potential confounding factors. RESULTS: Of the 536 patients included, 112 (20.9%) were referred for preoperative chemotherapy. Before the propensity score matching analysis, the groups were different in terms of age, hemoglobin level, node metastasis at clinical stage- status, and extent of gastrectomy. After the analysis, 112 patients were stratified for each group. Both were similar for all variables assigned in the score. Patients in the preoperative chemotherapy group had less advanced postoperative p staging (p=0.010), postoperative n staging (p<0.001), and pTNM stage (p<0.001). Postoperative complications, 30- and 90-days mortality were similar between both groups. Before the propensity score matching analysis, there was no difference in survival between the groups. After the analysis, patients in the preoperative chemotherapy group had better overall survival compared to upfront surgery group (p=0.012). Multivariate analyses demonstrated that American Society of Anesthesiologists III/IV category and the presence of lymph node metastasis were factors significantly associated with worse overall survival. CONCLUSIONS: Preoperative chemotherapy was associated with increased survival in gastric cancer. There was no difference in the postoperative complication rate and mortality compared to upfront surgery.

RESUMO RACIONAL: A ressecção cirúrgica continua sendo a principal modalidade terapêutica curativa para o câncer gástrico avançado. Recentemente, a associação de quimioterapia pré-operatória tem permitido a melhora dos resultados sem aumentar as complicações cirúrgicas. OBJETIVOS: Avaliar os resultados cirúrgicos e oncológicos da quimioterapia pré-operatória em um cenário do mundo real. MÉTODOS: Realizou-se uma revisão retrospectiva de pacientes com câncer gástrico submetidos à gastrectomia. Os pacientes foram divididos em dois grupos para análise: cirurgia inicial e quimioterapia pré-operatória. A análise por escore de propensão, incluindo 9 variáveis, foi aplicada para ajustar possíveis fatores de confusão. RESULTADOS: Dos 536 pacientes incluídos, 112 (20,9%) foram encaminhados para quimioterapia pré-operatória. Antes da análise por escore de propensão, os grupos eram diferentes em termos de idade, nível de hemoglobina, status de node metastasis at clinical stage e extensão da gastrectomia. Após a análise, 112 pacientes foram estratificados para cada grupo. Ambos foram semelhantes para todas as variáveis atribuídas no escore. O grupo da quimioterapia pré-operatória apresentou estágios postoperative p staging (p=0,010), postoperative n staging (p<0,001) e pTNM menos avançados (p<0,001). As complicações pós-operatórias e a mortalidade em 30 e 90 dias foram semelhantes entre os grupos. Antes da análise por escore de propensão, não houve diferença na sobrevida entre os dois grupos. Após a análise, o grupo da quimioterapia pré-operatória apresentou melhor sobrevida global em comparação ao grupo da cirurgia inicial (p=0,012). As análises multivariadas demostraram que a categoria American Society of Anesthesiologists III/IV e a metástase linfonodal foram fatores significativamente associados à pior sobrevida global. CONCLUSÕES: A quimioterapia pré-operatória foi associada à maior sobrevida no câncer gástrico. Não houve diferença na taxa de complicações pós-operatórias e mortalidade em comparação com a cirurgia inicial.

Intraperitoneal chemotherapy for gastric cancer with peritoneal carcinomatosis: study protocol of a phase ii trial / Quimioterapia intraperitoneal para o câncer gástrico com carcinomatose peritoneal: protocolo de estudo de um ensaio de fase ii

ABSTRACT BACKGROUND: Peritoneal carcinomatosis in gastric cancer is considered a fatal disease, without expectation of definitive cure. As systemic chemotherapy is not sufficient to contain the disease, a multimodal approach associating intraperitoneal chemotherapy with surgery may represent an alternative for these cases. AIMS: The aim of this study was to investigate the role of intraperitoneal chemotherapy in stage IV gastric cancer patients with peritoneal metastasis. METHODS: This study is a single institutional single-arm prospective clinical trial phase II (NCT05541146). Patients with the following inclusion criteria undergo implantation of a peritoneal catheter for intraperitoneal chemotherapy: Stage IV gastric adenocarcinoma; age 18-75 years; Peritoneal carcinomatosis with peritoneal cancer index<12; Eastern Cooperative Oncology Group 0/1; good clinical status; and lab exams within normal limits. The study protocol consists of four cycles of intraperitoneal chemotherapy with paclitaxel associated with systemic chemotherapy. After treatment, patients with peritoneal response assessed by staging laparoscopy undergo conversion gastrectomy. RESULTS: The primary outcome is the rate of complete peritoneal response. Progression-free and overall survivals are other outcomes evaluated. The study started in July 2022, and patients will be screened for inclusion until 30 are enrolled. CONCLUSIONS: Therapies for advanced gastric cancer patients have been evaluated in clinical trials but without success in patients with peritoneal metastasis. The treatment proposed in this trial can be promising, with easy catheter implantation and ambulatory intraperitoneal chemotherapy regime. Verifying the efficacy and safety of paclitaxel with systemic chemotherapy is an important progress that this study intends to investigate.

RESUMO RACIONAL: A carcinomatose peritoneal no câncer gástrico é considerada uma doença fatal, sem expectativa de cura definitiva. Como a quimioterapia sistêmica não é suficiente para conter a doença, uma abordagem multimodal associando a quimioterapia intraperitoneal à cirurgia pode representar uma alternativa para esses casos. OBJETIVOS: Investigar o papel da quimioterapia intraperitoneal em pacientes com câncer gástrico estágio IV com metástases peritoneais. MÉTODOS: Trata-se de um ensaio clínico prospectivo unicêntrico, braço único, fase II (NCT05541146). Pacientes com os seguintes critérios de inclusão serão submetidos à implantação de cateter peritoneal para quimioterapia intraperitoneal: adenocarcinoma gástrico estágio IV; idade 18-75 anos; carcinomatose peritoneal com índice de câncer peritoneal<12; ECOG 0/1; bom estado clínico e exames laboratoriais dentro da normalidade. O protocolo do estudo consiste em 4 ciclos de quimioterapia intraperitoneal com Paclitaxel associado à quimioterapia sistêmica. Após o tratamento, os pacientes com resposta peritoneal avaliada por laparoscopia serão submetidos à gastrectomia de conversão. RESULTADOS: O desfecho primário é a taxa de resposta peritoneal completa. A sobrevida livre de progressão e global são outros desfechos avaliados. O estudo foi iniciado em julho de 2022 e os pacientes serão selecionados para inclusão até que 30 sejam inscritos. CONCLUSIONS: Terapias para pacientes com câncer gástrico avançado foram avaliadas em ensaios clínicos, mas sem sucesso em pacientes com metástase peritoneal. O tratamento proposto neste estudo pode ser promissor, com fácil implantação do cateter e regime de quimioterapia intraperitoneal ambulatorial. Verificar a eficácia e segurança do Paclitaxel associado à quimioterapia sistêmica é um progresso importante que o presente estudo pretende investigar.

Short-Term Surgical Outcomes of Robotic Gastrectomy Compared to Open Gastrectomy for Patients with Gastric Cancer: a Randomized Trial.

BACKGROUND: Robotic gastrectomy (RG) has been shown to be a safe and feasible method in gastric cancer (GC) treatment. However, most studies are in Eastern cohorts and there is great interest in knowing whether the method can be used routinely, especially in the West. OBJECTIVES: The aim of this study was to compare the short-term surgical outcomes of D2-gastrectomy by RG versus open gastrectomy (OG). METHODS: Single-institution, open-label, non-inferiority, randomized clinical trial performed between 2015 and 2020. GC patients were randomized (1:1 allocation) to surgical treatment by RG or OG. Da Vinci Si platform was used. INCLUSION CRITERIA: gastric adenocarcinoma, stage cT2-4 cN0-1, potentially curative surgery, age 18-80 years, and ECOG performance status 0-1. EXCLUSION CRITERIA: emergency surgery and previous gastric or major abdominal surgery. Primary endpoint was short-term surgical outcomes. The study is registered at clinicaltrials.gov (NCT02292914). RESULTS: Of 65 randomized patients, 5 were excluded (3 palliatives, 1 obstruction and emergency surgery, and 1 for material shortage). Consequently, 31 and 29 patients were included for final analysis in the OG and RG groups, respectively. No differences were observed between groups regarding age, sex, BMI, comorbidities, ASA, and frequency of total gastrectomy. RG had similar mean number of harvested lymph nodes (p = 0.805), longer surgical time (p < 0.001), and less bleeding (p < 0.001) compared to OG. Postoperative complications, length of hospital stay, and readmissions in 30 days were equivalent between OG and RG. CONCLUSIONS: RG reduces operative bleeding by more than 50%. The short-term outcomes were non-inferior to OG, although surgical time was longer in RG.

Nonoperative vs Operative Management of Uncomplicated Acute Appendicitis: A Systematic Review and Meta-analysis.

Importance: Appendectomy remains the standard of care for uncomplicated acute appendicitis despite several randomized clinical trials pointing to the safety and efficacy of nonoperative management of this disease. A meta-analysis of randomized clinical trials may contribute to the body of evidence and help surgeons select which patients may benefit from surgical and nonsurgical treatment. Objective: To assess the efficacy and safety of nonoperative management vs appendectomy for acute uncomplicated appendicitis. Data Sources: A systematic review was conducted using indexed sources (Embase and PubMed) to search for published randomized clinical trials in English comparing nonoperative management with appendectomy in adult patients presenting with uncomplicated acute appendicitis. To increase sensitivity, no limits were set for outcomes reported, sex, or year of publication. All nonrandomized or quasi-randomized trials were excluded, and validated primers were used. Study Selection: Among 1504 studies imported for screening, 805 were duplicates, and 595 were excluded for irrelevancy. A further 96 were excluded after full-text review, mainly owing to wrong study design or inclusion of pediatric populations. Eight studies met the inclusion criteria and were selected for the meta-analysis. Data Extraction and Synthesis: Meta-extraction was conducted with independent extraction by multiple reviewers using the Covidence platform for systematic reviews and in accordance with PRISMA guidelines. Data were pooled by a random-effects model. Main Outcomes and Measures: Treatment success and major adverse effects at 30 days' follow-up. Results: The main outcome (treatment success proportion at 30 days of follow-up) was not significantly different in the operative and nonoperative management cohorts (risk ratio [RR], 0.85; 95% CI, 0.66-1.11). Likewise, the percentage of major adverse effects was similar in both cohorts (RR, 0.72; 95% CI, 0.29-1.79). However, in the nonoperative management group, length of stay was significantly longer (RR, 1.48; 95% CI, 1.26-1.70), and a median cumulative incidence of 18% of recurrent appendicitis was observed. Conclusions and Relevance: These results point to the general safety and efficacy of nonoperative management of uncomplicated acute appendicitis. However, this strategy may be associated with an increase in duration of hospital stay and a higher rate of recurrent appendicitis. This meta-analysis may help inform decision-making in nonoperative management of uncomplicated acute appendicitis.

Gastric cancer with microsatellite instability displays increased thymidylate synthase expression.

BACKGROUND: Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. METHODS: We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). RESULTS: Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. CONCLUSION: MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.

Multivisceral resection compared to standard gastrectomy for gastric adenocarcinoma: A propensity score-matching analysis.

BACKGROUND: Multivisceral resection (MVR) in locally advanced gastric cancer (GC) is a morbid procedure. However, the precise impact of removing additional organs remains controversial. This study aimed to compare the outcomes of MVR versus standard gastrectomy (SG) in an unbiased cohort. METHODS: Patients who underwent curative-intent surgery for gastric adenocarcinoma were considered. Those submitted to SG were compared to the ones who received MVR using Propensity Score Matching (PSM) analysis. RESULTS: A total of 685 GC patients were included (621 SG and 64 MVR). Groups were distinct concerning the extent of the gastrectomy, tumor size, pTNM, R0, postoperative complications, and 90-day mortality. After PSM, 57 patients were matched in each group. All variables assigned in the score were well matched. Postoperative complication, 90-day mortality, and overall survival (OS) became similar among groups. Age >65 years old and resection of two or more organs, besides the stomach, were factors associated with 90-day mortality. R1 and not received multimodal therapy were independent prognostic factors for worse OS. CONCLUSIONS: After PSM, the difference in morbidity, mortality, and survival of MVR compared to SG was no longer statistically significant, suggesting that MVR is an acceptable therapeutic strategy to patients with advanced GC.

Preoperative chemotherapy is a better strategy than upfront surgery in cT4 gastric cancer.

BACKGROUND: Chemotherapy (CMT) followed by surgery is recommended by Western countries for advanced gastric cancer (GC). However, cT4 GC usually undergoes upfront surgery, due to symptoms. This study aimed to evaluate if preoperative CMT is a better strategy than upfront surgery in cT4 GC. METHODS: All cT4 GCs who underwent curative gastrectomy were included. Patients were divided according to their initial treatment: upfront surgery (SURG) or CMT + SURG. RESULTS: Among the 226 GC initially staged as cT4, 150 underwent SURG and 76 CMT + SURG. Groups were similar concerning age, comorbidities, American Society of Anesthesiologists, gastrectomy performed, and postoperative complications. The CMT + SURG group had less advanced pTNM. Median overall survival (OS) was 32 and 58.5 months for SURG and CMT + SURG, respectively (p = 0.04). Patients who received perioperative or adjuvant CMT had better OS compared to surgery alone (49.4 vs. 15.9 months, p < 0.001). OS was similar for those receiving preoperative and adjuvant CMT. Non-CMT, pN+, and R1 resection were independent risk factors for worse OS. CONCLUSION: Multimodal treatment associating CMT with surgery, regardless of whether the approach is pre- or postoperative, is essential to improve the survival of cT4 GC. As tolerance to adjuvant treatment is reduced, preoperative CMT is a better strategy than upfront surgery in these patients.

Gastrectomy for elderly gastric cancer patients: A propensity score-matching analysis.

BACKGROUND: Although D2-gastrectomy is the most effective treatment for resectable gastric cancer (GC), it is unclear whether elderly patients have increased risk of morbidity and worse survival. This study aimed to compare the short- and long-term outcomes of older age (OA) patients with those of less advanced age (LAA). METHODS: GC patients undergoing curative gastrectomy were retrospectively analyzed and divided into two groups: OA (>75 years) and LAA (<75 years). Propensity score-matching (PSM) analysis using seven variables was conducted to reduce selection bias. RESULTS: Among 586 patients, 494 (84.3%) were classified as LAA and 92 (15.7%) as OA. OA patients had worse clinical status, higher rates of D1-lymphadenectomy, subtotal gastrectomy, and Lauren type; higher mortality and worse survival. No difference in pathological tumor-node-metastasis (pTNM) stage was observed between groups. Preoperative chemotherapy was performed more frequently in the LAA group. After PSM (92 OA: 92 LAA), all variables included in PSM were matched, and mortality rates and survival became similar between groups. In multivariate analysis, American Society of Anaesthesiologists score III/IV was an independent factor associated with a 90-day mortality after PSM. CONCLUSION: Gastrectomy in elderly GC patients has similar outcomes compared with younger ones. Clinical status and disease stage are more important than the patient's age.

Characteristics of postintubation dysphagia in ICU patients in the context of the COVID-19 outbreak: A report of 920 cases from a Brazilian reference center.

The purpose of this research was to identify risk factors that were independently related to the maintenance of a swallowing dysfunction in patients affected by critical COVID-19. We conducted a prospective observational cohort study of critical patients with COVID-19, who were admitted to a COVID-19 dedicated intensive care unit (ICU) and required prolonged orotracheal intubation (≥48 hours). Demographic and clinical data were collected at ICU admission and/or at hospital discharge or in-hospital death. Swallowing data was based on The Functional Oral Intake Scale (FOIS) and was collected at two distinct moments: initial swallowing assessment and at patient outcome. Patients were divided into two groups according to their FOIS level assigned on the last swallowing assessment: in-hospital resolved dysphagia-patients with FOIS levels 6 and 7; non-resolved dysphagia at hospital outcome-patients with FOIS levels 1 to 5. Nine hundred and twenty patients were included in our study. Results of the multivariate logistic regression model for the prediction of non-resolved dysphagia at hospital outcome in critical COVID-19 patients. indicated that increasing age (p = 0.002), severity at admission (p = 0.015), body mass index (p = 0.008), use of neuromuscular blockers (p = 0.028), presence of neurologic diseases (p = 0.038), presence of Diabetes Mellitus (p = 0.043) and lower FOIS levels on the initial swallowing assessment (p<0.001) were associated with higher chances of presenting dysphagia at hospital outcome. Critical patients with COVID-19 may experience post-acute COVID-19 dysphagia, indicating the need to prepare for the care/rehabilitation of these patients.