BRUNO ZILBERSTEIN

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Departamento de Gastroenterologia, Faculdade de Medicina - Docente

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Assunto: Stomach neoplasms ×

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  • article 3 Citação(ões) na Scopus
    RECURRENCE IN PN0 GASTRIC CANCER: RISK FACTORS IN THE OCCIDENT
    (2021) NOBRE, Karolyne Ernesto Luiz; PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; RIBEIRO, Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; DIAS, Andre Roncon
    Background: Nearly 10% of node negative gastric cancer patients who underwent curative surgery have disease recurrence. Western data is extremely poor on this matter and identifying the risk factors that associate with relapse may allow new strategies to improve survival. Aim: Verify the clinical and pathological characteristics that correlate with recurrence in node negative gastric cancer. Methods: All gastric cancer patients submitted to gastrectomy between 2009 and 2019 at our institution and pathologically classified as N0 were considered. Their data were available in a prospective database. Inclusion criteria were: gastric adenocarcinoma, node negative, gastrectomy with curative intent, R0 resection. Main outcomes studied were: disease-free survival and overall survival. Results: A total of 270 patients fulfilled the inclusion criteria. Mean age was 63-year-old and 155 were males. Subtotal gastrectomy and D2 lymphadenectomy were performed in 64% and 74.4%, respectively. Mean lymph node yield was 37.6. Early GC was present in 54.1% of the cases. Mean follow-up was 40.8 months and 19 (7%) patients relapsed. Disease-free survival and overall survival were 90.9% and 74.6%, respectively. Independent risk factors for worse disease-free survival were: total gastrectomy, lesion size >= 3.4 cm, higher pT status and <16 lymph nodes resected. Conclusion: In western gastric cancer pN0 patients submitted to gastrectomy, lymph node count <16, pT3-4 status, tumor size >= 3.4 cm, total gastrectomy and presence of lymphatic invasion, are all risk factors for disease relapse.
  • article 30 Citação(ões) na Scopus
    Carnoy's solution increases the number of examined lymph nodes following gastrectomy for adenocarcinoma: a randomized trial
    (2016) DIAS, Andre Roncon; PEREIRA, Marina Alessandra; MELLO, Evandro Sobroza; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; RIBEIRO JUNIOR, Ulysses
    Pathological examination of a minimum of 16 lymph nodes is recommended following surgery for gastric adenocarcinoma, despite this a longer survival is expected when 30 or more lymph nodes are examined. Small lymph nodes are difficult to identify, and fat-clearing solutions have been proposed to improve this, but there is no evidence of their clinical benefit. Fifty D2 subtotal gastrectomy specimens were randomized for fixation in Carnoy's solution (CS) or 10 % neutral buffered formalin (NBF), with subsequent fat dissection. After dissection, the residual fat from the NBF group, instead of being discarded, was immersed in CS and dissected again. Data from 25 D2 subtotal gastrectomies performed before the study were also analyzed. The mean number of examined lymph nodes was 50.4 and 34.8 for CS and NBF, respectively (p < 0.001). Missing lymph nodes were found in all cases from the residual fat group (mean of 16.9), and in eight of them (32 %) metastatic lymph nodes were present; this allowed the upstaging of two patients. Lymph nodes in the CS group were smaller than those in the NBF group (p = 0.01). The number of retrieved lymph nodes was similar among the NBF and Retrospective groups (p = 0.802). Compared with NBF, CS increases lymph node detection following gastrectomy and allows a more accurate pathological staging. No influence of the research protocol on the number of examined lymph nodes was observed.
  • article
    Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer
    (2022) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; MORAES, Rafael Dyer Rodrigues de; RIBEIRO, Renan Ribeiro E.; ALVES, Venancio Avancini Ferreira; ZILBERSTEIN, Bruno; MELLO, Evandro Sobroza de; JR, Ulysses Ribeiro
    Objective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune -related score.Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC).Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival.Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.
  • article 15 Citação(ões) na Scopus
    Risk factors associated with the development of gastric cancer - case-control study
    (2018) RAMOS, Marcus Fernando Kodama Pertille; RIBEIRO JUNIOR, Ulysses; VISCONDI, Juliana Kodaira Yukari; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; ELUF-NETO, Jose
  • article 18 Citação(ões) na Scopus
    Surgical outcomes of gastrectomy with D1 lymph node dissection performed for patients with unfavorable clinical conditions
    (2019) RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; YAGI, Osmar Kenji; ZAIDAN, Evelise Pelegrinelli; RIBEIRO-JUNIOR, Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, Ivan
    Background: Gastric cancer (GC) patients with advanced age and/or multiple morbidities have limited expected survival and may not benefit from extended lymph node resection. The aim of this study was to evaluate the surgical outcomes of these GC patients who underwent gastrectomy with Dl dissection. Methods: We retrospectively reviewed all GC patients who underwent gastrectomy with curative intent from 2009 to 2017. The decision to perform D1 was based on preoperative multidisciplinary meeting, and/or intraoperative clinical judgment. Results: Among 460 enrolled patients, 73 (15.9%) underwent D1 lymphadenectomy and 387 (84.1%) D2 lymphadenectomy. Male gender, older age, American Society of Anesthesiologists score (ASA) III/IV, higher neutrophil-to-lymphocyte ratio (NLR) and higher Charlson Comorbidity Index (CCI) were more common in the D1 group. Postoperative major complications were significantly higher in D1 group (24.7% vs 12.4%, p < 0.001) and mostly related to clinical complications. Locoregional recurrence was higher in the D1 group (53.8% vs 39.5%, p = 0.330) however, without statistical significance. No difference was found in disease-free survival (DFS) between D1 and D2 patients with positive lymph nodes (p = 0.192), whereas overall survival was longer in the D2 group (p < 0.001). Multivariate analysis showed a statistically significant impact on survival of age >= 70 years, CCI >= 5, total gastrectomy, D1 lymphadenectomy and advanced stages (III/IV). Conclusions: Frail patients had high surgical mortality even when submitted to D1 dissection. DFS was comparable to D2. Extent of lymphadenectomy in high-risk patients should take in account the expectation of a decrease in surgical risk with the possibility of impairment of long-term survival.
  • article 1 Citação(ões) na Scopus
    IMPACT OF AGING IN THE SURGICAL OUTCOMES OF GASTRIC CANCER PATIENTS
    (2021) DIAS, Andre Roncon; PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; RIBEIRO JR, Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, Ivan
    ABSTRACT BACKGROUND: As age advances, a higher burden of comorbidities and less functional reserve are expected, however, the impact of aging in the surgical outcomes of gastric cancer (GC) patients is unknown. OBJECTIVE: The aim of this study is to evaluate surgical outcomes of GC patients according to their age group. METHODS: Patients submitted to gastrectomy with curative intent due to gastric adenocarcinoma were divided in quartiles. Each group had 150 patients and age limits were: ≤54.8, 54.9-63.7, 63.8-72, >72. The outcomes assessed were: postoperative complications (POC), 90-day postoperative mortality, disease-free survival (DFS) and overall survival (OS). RESULTS: Major surgical complications were 2.7% in the younger quartile vs 12% for the others (P=0.007). Major clinical complications raised according to the age quartile: 0.7% vs 4.7% vs 5.3% vs 7.3% (P<0.042). ASA score and age were independent risk factors for major POC. The 90-day mortality progressively increased according to the age quartile: 1.3% vs 6.0% vs 7.3% vs 14% (P<0.001). DFS was equivalent among quartile groups, while OS was significantly worse for those >72-year-old. D2 lymphadenectomy only improved OS in the three younger quartiles. Age >72 was an independent risk factor for worse OS (hazard ratio of 1.72). CONCLUSION: Patients <55-year-old have less surgical complications. As age progresses, clinical complications and 90-day mortality gradually rise. OS is worse for those above age 72, and D2 lymphadenectomy should be individualized after this age.
  • article
    Preoperative albumin-bilirubin score is a prognostic factor for gastric cancer patients after curative gastrectomy
    (2023) SZOR, Daniel Jose; PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; TUSTUMI, Francisco; DIAS, Andre Roncon; ZILBERSTEIN, Bruno; RIBEIRO, Ulysses
    BACKGROUNDAlbumin-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.AIMTo evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative treatment.METHODSPatients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective database. ALBI score was calculated as follows: (log10 bilirubin x 0.660) + (albumin x -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.RESULTSA 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.CONCLUSIONThe 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.
  • article 8 Citação(ões) na Scopus
    Simplified technique for reconstruction of the digestive tract after total and subtotal gastrectomy for gastric cancer
    (2014) ZILBERSTEIN, Bruno; JACOB, Carlos Eduardo; BARCHI, Leandro Cardoso; YAGI, Osmar Kenji; RIBEIRO-JR, Ulysses; COIMBRA, Brian Guilherme Monteiro Marta; CECCONELLO, Ivan
    BACKGROUND: Laparoscopic surgery has been increasingly applied to gastric cancer surgery. Gastrointestinal tract reconstruction totally done by laparoscopy also has been a challenge for those who developed this procedure. AIM - To describe simplified reconstruction after total or subtotal gastrectomy for gastric cancer by laparoscopy and the results of its application in a series of cases. METHODS - In the last four years, 75 patients were operated with gastric cancer and two with GIST. Thirty-four were women and 43 men. The age ranged from 38 to 77 years with an average of 55 years. In two patients with GIST a total and a subtotal gastrectomy were performed. In the other 75 patients were done 21 total gastrectomies and 54 subtotal. In all cancers, gastrectomy with D2 lymphadenectomy was completed with at least 37 lymph nodes removed. Was used in these operations a modified laparoscopic technique proposed by the authors consisting in a latero lateral esophagojejunal anastomosis with linear stapler in TG as well in STG, and reconstruction of the digestive continuity also in the upper abdomen. RESULTS - The intraoperative and immediate postoperative course were uneventful, except for one case of bleeding due to an opening clip, necessitating re-intervention. The operative time was 300 minutes, with no difference between total or subtotal gastrectomy. The number of lymph nodes removed varied from 28 to 69, averaging 37. Postoperative staging showed one case in T4 N2 M0; 13 in T2 N0 MO; 27 in T2 N1 M0; 24 in T3 N1 M0 and 10 in T3 N2 M0. Complication in only one case was observed on the 10th postoperative day with a small anastomotic leakage in esophagojejunal anastomose with spontaneous closure. CONCLUSION - The patient's evolution with no complications, no mortality and just one small anastomotic leakage with no systemic repercussions is a strong indication of the liability and feasibility of this innovative technical method.
  • article 2 Citação(ões) na Scopus
    Remnant gastric cancer: a neglected group with high potential for immunotherapy
    (2020) RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi de; RIBEIRO, Renan Ribeiro e; CARDILI, Leonardo; MELLO, Evandro Sobroza de; ZILBERSTEIN, Bruno; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan
    Purpose The importance of targeted therapy and interest in the study of predictive markers in gastric cancer (GC) have increased in recent years with the use of anti-HER2 therapy and immunotherapy with anti-PD1/PD-L1 for microsatellite instability (MSI) and PD-L1 + tumors. However, the behavior of remnant GC (RGC) in this scenario is poorly reported. Thus, this study aims to evaluate the clinicopathological characteristics and prognosis of RGC and its association with the expression of current markers for targeted therapy. Methods All RGC resections performed in a single center from 2009 to 2019 were retrospectively reviewed. As a comparison group, 53 primary proximal GC (PGC) who underwent total D2-gastrectomy were selected. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry. Combined Positive Score (CPS) was used to determine PD-L1 positivity. Results A total of 40 RGC were included. RGC patients were older (p = 0.001), had lower BMI (p = 0.001) and number of resected lymph nodes (p < 0.001) compared to the PGC. Regarding markers expression, MSI was higher in RGC than PGC (27.5% vs 9.4%,p = 0.022). The frequency of CPS-positive was 32.5% and 26.4% in RGC and PGC, respectively (p = 0.522). HER2 positivity was 17.5% and 22.6% for RGC and PGC, respectively (p = 0.543). In survival analysis, DFS was better for RGC CPS-positive than RGC CPS-negative (p = 0.039) patients. There was no difference in survival considering MSI status. Conclusion RGC had higher incidence of MSI than PGC, and CPS-positive RGC was associated with better survival. The immunological profile of RGC patients suggests that they would be good candidates for immunotherapy.
  • article 12 Citação(ões) na Scopus
    Gastric partitioning for the treatment of malignant gastric outlet obstruction
    (2019) RAMOS, Marcus Fernando Kodama Pertille; BARCHI, Leandro Cardoso; OLIVEIRA, Rodrigo Jose de; PEREIRA, Marina Alessandra; MUCERINO, Donato Roberto; RIBEIRO JR., Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, Ivan
    BACKGROUND Gastric outlet obstruction (GOO) is one of the main complications in stage IV gastric cancer patients. This condition is usually managed by gastrojejunostomy (GJ). However, gastric partitioning (GP) has been described as an alternative to overcoming possible drawbacks of GJ, such as delayed gastric emptying and tumor bleeding. AIM To compare the outcomes of patients who underwent GP and GJ for malignant GOO. METHODS We retrospectively analyzed 60 patients who underwent palliative gastric bypass for unresectable distal gastric cancer with GOO from 2009 to 2018. Baseline clinicopathological characteristics including age, nutritional status, body mass index, and performance status were evaluated. Obstructive symptoms were graded according to GOO score (GOOS). Surgical outcomes evaluated included duration of the procedure, surgical complications, mortality, and length of hospital stay. Acceptance of oral diet after the procedure, weight gain, and overall survival were the long-term outcomes evaluated. RESULTS GP was performed in 30 patients and conventional GJ in the other 30 patients. The mean follow-up was 9.2 mo. Forty-nine (81.6%) patients died during that period. All variables were similar between groups, with the exception of worse performance status in GP patients. The mean operative time was higher in the GP group (161.2 vs 85.2 min, P < 0.001). There were no differences in postoperative complications and surgical mortality between groups. The median overall survival was 7 and 8.4 mo for the GP and GJ groups, respectively (P = 0.610). The oral acceptance of soft solids (GOOS 2) and low residue or full diet (GOOS 3) were reached by 28 (93.3%) GP patients and 22 (75.9%) GJ patients (P = 0.080). Multivariate analysis demonstrated that GOOS 2 and GOOS 3 were the main prognostic factors for survival (hazard ratio: 8.90, 95% confidence interval: 3.3823.43, P < 0.001). CONCLUSION GP is a safe and effective procedure to treat GOO. Compared to GJ, it provides similar surgical outcomes with a trend to better solid diet acceptance by patients.