ANDRE RONCON DIAS
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject PREOPERATIVE CHEMOTHERAPY VERSUS UPFRONT SURGERY FOR STAGE CT4 GASTRIC CANCER: WHAT IS THE BEST STRATEGY?(2022) DIAS, Andre R.; PEREIRA, Marina A.; RAMOS, Marcus F.; RIBEIRO, Ulysses; ZILBERSTEIN, Bruno; NAHAS, Sergio Carlos- INTRAPERITONEAL CHEMOTHERAPY FOR GASTRIC CANCER WITH PERITONEAL CARCINOMATOSIS: STUDY PROTOCOL OF A PHASE II TRIAL(2023) RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; CHARRUF, Amir Zeide; VICTOR, Carolina Ribeiro; GREGORIO, Joao Vitor Antunes Marques; ALBAN, Luciana Bastos Valente; MONIZ, Camila Motta Venchiarutti; ZILBERSTEIN, Bruno; MELLO, Evandro Sobroza De; HOFF, Paulo Marcelo Gehm; JUNIOR, Ulysses Ribeiro; DIAS, Andre RonconBackground: 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.
- 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 RibeiroObjective: 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.
- Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy(2018) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; FARAJ, Sheila Friedrich; CIRQUEIRA, Cinthya dos Santos; MELLO, Evandro Sobroza de; ZILBERSTEIN, Bruno; ALVES, Venancio Avancini Ferreira; RIBEIRO JR., UlyssesObjective: Adjuvant chemotherapy with 5-fluorouracil (5-FU) has been widely used in gastric cancer (GC) patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase (TS), and high levels of TS correlate with resistance to treatment with fluoropyrimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods: We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry (IHC) in tumor cells by tissue microarray (TMA). TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score: negative, low and high. Results: TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age (P=0.007), high neutrophil/lymphocyte ratio (P=0.048), well/moderately differentiated histology (P=0.001), intestinal Lauren type (P<0.001) and absence of perineural invasion (P=0.003). Among 285 patients, 133 stage II/III patients (46.7%) received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival (DFS) in stage III GC patients who received 5-FU-based chemotherapy (P=0.007). Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. Conclusions: High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.
- FAILURE TO RESCUE AFTER GASTRECTOMY: A NEW INDICATOR OF SURGICAL QUALITY(2023) HONG, Stefany; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; JR, Ulysses Ribeiro; D'ALBUQUERQUE, Luiz Augusto Carneiro; RAMOS, Marcus Fernando Kodama PertilleBackground: The main treatment modality for gastric cancer is surgical resection with lymphadenectomy. Despite advances in perioperative care, major surgical complications can occur in up to 20% of cases. To determine the quality of surgical care employed, a new indicator called failure to rescue (FTR) was proposed, which assesses the percentage of patients who die after complications occur.Aims: To assess the rate of FTR after gastrectomy and factors associated with its occurrence.Methods: Patients with gastric cancer who underwent gastrectomy with curative intent were retrospectively evaluated. According to the occurrence of postoperative complications, patients were divided into FTR group (grade V complications) and rescued group (grade III/IV complications).Results: Among the 731 patients, 114 had major complications. Of these patients, 76 (66.7%) were successfully treated for the complication (rescued group), while 38 (33.3%) died (FTR group). Patients in the FTR group were older (p=0.008; p<0.05), had lower levels of hemoglobin (p=0.021; p<0.05) and albumin (p=0.002; p<0.05), and a higher frequency of ASA III/IV (p=0.033; p<0.05). There were no differences between the groups regarding surgical and pathological characteristics. Clinical complications had a higher mortality rate (40.0% vs 30.4%), with pulmonary complications (50.2%) and infections (46.2%) being the most lethal. Patients with major complications grade III/IV had worse survival than those without complications.Conclusions: The FTR rate was 33.3%. Advanced age, worse performance, and nutritional parameters were associated with FTR.
- 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, UlyssesBACKGROUNDAlbumin-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.
- STAGING LAPAROSCOPY IS STILL A VALUABLE TOOL FOR OPTIMAL GASTRIC CANCER MANAGEMENT(2022) SAKAMOTO, Erica; RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; RIBEIRO JUNIOR, Ulysses; ZILBERSTEIN, Bruno; NAHAS, Sergio CarlosComplete 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 RESUMO -Racional: O tratamento de escolha para pacientes com hipertensao portal detect it. AI M: The aim of this study was to evaluate the role of staging laparoscopy in the esqustossomotica com sangramento de vriz e a desconexao azigo-portal mais staging of advanced gastric cancer patients in a Wes tern tertiary cancer center. METHODS: A total oesplenectomiaf 130 p atie(DAPE)nts with gassociadaastric aa denterapiocarcinmendoscopica.a who undPorem,erwe nt sestudostagin g lamostrmparos copyaumento from do calibre das varizes em alguns pacientes durante o seguimeto em lngo prazo. Objtivo: 2009 to 2020 were evaluated from a prospective database. Clinicopathological characteristics Avaliar o impacto da DAPE e tratamento endoscopico pos-operatorio no comportamento were analyzed to identify factors associated with the presence of peritoneal metastasis and were also evaluated the accuracy and strength of agreement between computed das varizes esofagicas e recidiva hemorragica, de pacientes esquistossomoticos. Metodos: tomography and staging laparoscopy in detecting peritoneal metastasis and the change in Form sudados 36 pacientes om seguimento superio a cinco anos, distribuios em treatment strategy after the procedure. RESULTS: The peritoneal metastasis was identified indois 6 6 (5grupos:0.76 %) quedapati edant s. Thpressaoe se nsiportaltivit y, sabaixopec ifideci ty,30% an ed acimacura cdey of30% co mputecomparadosd tom ogcomrap ho y calibre das varizes esofagicas no pos-operatorio precoce e tardio alem do indie e recidiva in detecting peritoneal metastasis were 51.5, 87.5, and 69.2%, respectively. According to the hemorragica. Resultados 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 esofagicas que, durante o seguimento aumentaram de calibre e foram controladas com 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 oa vided ucomportamentonnecessa rydo l apacalibreroto mdasy, andvarizes 8 p atnoie nts, whopos-operatorio were p revioprecoceusly conemnsi detardioed stanemge IVos b indies de recidiva hemorragica. Conclusao 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.
- Gastric trichobezoar(2017) SZOR, Daniel Jose; DIAS, Andre RonconKey Clinical Message Trichobezoar is a rare gastrointestinal pathology, but should be considered in patients with abdominal mass and previous history of trichophagia. In physical examination, it is important to verify signs of alopecia. Minimally invasive surgery is a secure method to remove the specimen from the stomach.
conferenceObject MULTIVISCERAL RESECTION COMPARED TO STANDARD GASTRECTOMY FOR GASTRIC ADENOCARCINOMA: A PROPENSITY SCORE-MATCHING ANALYSIS(2022) DIAS, Andre R.; PEREIRA, Marina A.; RAMOS, Marcus F.; RIBEIRO, Ulysses; ZILBERSTEIN, Bruno; NAHAS, Sergio Carlos- Minimally invasive surgery for gastric cancer in Brazil: current status and perspectives-a report from the Brazilian Laparoscopic Oncologic Gastrectomy Group (BLOGG)(2017) KASSAB, Paulo; COSTA JR., Wilson Luiz da; JACOB, Carlos Eduardo; CORDTS, Roberto de Moraes; CASTRO, Osvaldo Antonio Prado; BARCHI, Leandro Cardoso; CECCONELLO, Ivan; CHARRUF, Amir Zeide; COIMBRA, Felipe Jose Fernandez; CURY, Antonio Moris; DINIZ, Alessandro Landskron; FARIAS, Igor Correia de; FREITAS JR., Wilson Rodrigues de; GODOY, Andre Luis de; ILIAS, Elias Jirjoss; MALHEIROS, Carlos Alberto; RAMOS, Marcus Fernando Kodama Pertille; RIBEIRO, Heber Salvador de Castro; DIAS, Andre Roncon; THULER, Fabio Rodrigues; YAGI, Osmar Kenji; LOURENCO, Laercio Gomes; ZILBERSTEIN, BrunoThe minimally invasive surgery for gastric cancer in Brazil has begun about two years after the first laparoscopic gastrectomy (LG) performed by Kitano in Japan, in 1991. Although the report of first surgeries shows the year of 1993, there was no dissemination of the technique until the years 2010. At that time with the improvement of optical devices, laparoscopic instruments and with the publications coming from Asia, several Brazilian surgeons felt encouraged to go to Korea and Japan to learn the standardization of the LG. After that there was a significant increase in that type of surgery, especially after the IRCAD opened a branch in Brazil. The growing interest for the subject led some services to begin their own experience with the LG and, since the beginning, the results were similar with those found in the open surgery. Nevertheless, there were some differences with the papers published initially in Japan and Korea. In those countries, the surgeries were laparoscopic assisted, meaning that, in the majority of cases, the anastomoses were done through a mini-incision in the end of the procedure. In Brazil since the beginning it was performed completely through laparoscopic approach due to the skills acquired by Brazilian surgeons in bariatric surgeries. Another difference was the stage. While in the east the majority of cases were done in T1 patients, in Brazil, probably due to the lack of early cases, the surgeries were done also in advanced cases. The initial experience of Zilberstein et al. revealed low rates of morbidity without mortality. Comparing laparoscopic and open surgery, the group from Barretos/IRCAD showed shorter surgical time (216x255 minutes), earlier oral or enteral feeding and earlier hospital discharge, with a smaller number of harvested lymph nodes (28 in laparoscopic against 33 in open surgery). There was no significant difference regarding morbidity, mortality and reoperation rate. In the first efforts to publish a multicentric study the Brazilian Gastric Cancer Association (BGCA) collected data from three institutions analyzing 148 patients operated from 2006 to 2016. There were 98 subtotal, 48 total and 2 proximal gastrectomies. The anastomoses were totally laparoscopic in 105, laparoscopic assisted in 21, cervical in 2, and 20 open (after conversion). The reconstruction methods were: 142 Roux-en-Y, two Billroth I, and three other types. The conversion rate was 13.5% (20/148). The D2 dissection was performed in 139 patients. The mean number of harvested lymph nodes was 34.4. If we take only the D2 cases the mean number was 39.5. The morbidity rate was 22.3%. The mortality was 2.7%. The stages were: IA-59, IB-14, IIA-11, IIB-15, IIIA-9, IIIB-19, IIIC-11 and stage IV-three cases. Four patients died from the disease and 10 are alive with disease. The participating services have already begun the robotic gastrectomy with satisfactory results. The intention of this group is to begin now a prospective multicentric study to confirm the data already obtained with the retrospective studies.