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
11 resultados
Resultados de Busca
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- Gastric cancer with microsatellite instability displays increased thymidylate synthase expression(2022) PEREIRA, Marina A.; DIAS, Andre R.; RAMOS, Marcus F. K. P.; CARDILI, Leonardo; MORAES, Rafael D. R.; ZILBERSTEIN, Bruno; NAHAS, Sergio C.; MELLO, Evandro S.; JR, Ulysses RibeiroBackground 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.
- Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression(2021) PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi de; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; MORAES, Rafael Dyer Rodrigues; ZILBERSTEIN, Bruno; NAHAS, Sergio Carlos; JR, Ulysses Ribeiro; MELLO, Evandro Sobroza deBackground Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. Methods All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. Results Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. Conclusion CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.
- Preoperative chemotherapy is a better strategy than upfront surgery in cT4 gastric cancer(2022) DIAS, Andre R.; PEREIRA, Marina A.; RAMOS, Marcus F. K. P.; JR, Ulysses Ribeiro; ZILBERSTEIN, Bruno; NAHAS, Sergio C.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.
- Impact of neoadjuvant chemotherapy on surgical and pathological results of gastric cancer patients: A case-control study(2020) CHARRUF, Amir Zeide; RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; CASTRIA, Tiago Biachi de; ZILBERSTEIN, Bruno; CECCONELO, Ivan; RIBEIRO, UlyssesBackground and Objective Neoadjuvant chemotherapy (NACT) followed by radical surgery represents a treatment option for patients with advanced gastric cancer (GC). This case-control study aimed to evaluate the clinicopathological characteristics and surgical outcomes of GC patients who received NACT, and its impact on survival. Methods We retrospectively reviewed all patients with GC who underwent gastrectomy. A total of 45 cases with NACT were matched with consecutive 45 patients who underwent upfront gastrectomy for the following characteristics: gender, age, gastrectomy type, lymphadenectomy extent, American Society of Anesthesiologists class, histological type, cT and cN. Results NACT group had smaller tumors (4.9 vs 6.8 cm P = .006), lower lymphatic invasion rate (40% vs 73.3%, P = .001), lower venous invasion rate (18% vs 46.7%, P = .003) and lower perineural invasion rate (35% vs 77.8%, P < .0001). The ypTNM stage was lower in patients treated with NACT (P < .001). The major postoperative complication (POC) rate was lower in NACT patients (6.7% vs 24.4%, P = .02), as was hospital length of stay (10.8 vs 17 days, P = .005). Conclusions NACT allowed nodal and tumor downstaging. In addition, patients who underwent NACT had fewer POC and shorter length of hospital stay.
- Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer(2018) PEREIRA, Marina A.; RAMOS, Marcus F. K. P.; FARAJ, Sheila F.; DIAS, Andre R.; YAGI, Osmar K.; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; ALVES, Venancio A. F.; MELLO, Evandro S. de; RIBEIRO JR., UlyssesBackground and ObjectivesGastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. MethodsWe evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. ResultsEBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P=0.032), proximal location (P<0.001), undetermined Lauren type (P<0.001), poorly differentiated histology (P=0.043) and severe inflammatory infiltrate (P<0.001). MSI-tumors were associated to older age (P=0.002), subtotal gastrectomy (P=0.004), pN0 (P=0.024) and earlier TNM stage (P=0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P<0.001). MSI was associated to better survival outcomes. ConclusionEBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.
- Multivisceral resection vs standard gastrectomy for gastric adenocarcinoma(2020) DIAS, Andre R.; PEREIRA, Marina A.; OLIVEIRA, Rodrigo J.; RAMOS, Marcus F. K. P.; SZOR, Daniel J.; RIBEIRO, Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, IvanIntroduction Multivisceral resection (MVR) is potentially curative for selected gastric cancer patients, supposedly at the cost of increased complications. However, current data comparing MVR to standard gastrectomy (SG) is lacking. Objectives Compare complications and survival after MVR and SG. Methods In a retrospective cohort of 1015 patients with gastric adenocarcinoma, 58 underwent MVR and 466 SG. Groups were compared concerning their characteristics, complications, and survival. Results One hundred seventy-six patients had postoperative complications. Major complications were more frequent after MVR (P = .002). Surgical mortality was 8.6% and 4.9% for MVR and SG (P = .221). Older age, higher morbidities, and MVR were independent risk factors for major complications. The odds ratio for major complications was 5.89 for MVR with one or two organs and 38.01 for MVR with three or more organs. The pancreas was the most commonly removed organ and pT4b disease were confirmed in 34 (58.6%) of the MVR cases. Disease-free survival (DFS) was lower in MVR patients (51% vs 77.8%; P < .001), being worse according to the number of organs resected. In pN+ patients, DFS was worse after MVR. DFS was equivalent to pT4b and non-pT4b in the MVR group. Conclusions Increased morbidity and lower survival are expected for gastric cancer patients undergoing MVR.
- Reply to: ""Association between neutrophil-lymphocyte ratio and prognosis after potentially curative resection for gastric cancer""(2018) SZOR, Daniel J.; DIAS, Andre R.; PEREIRA, Marina A.; RAMOS, Marcus F. K. P.; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; RIBEIRO JR., Ulysses
- Neutrophil-lymphocyte ratio is associated with prognosis in patients who underwent potentially curative resection for gastric cancer(2018) SZOR, Daniel Jose; DIAS, Andre Roncon; PEREIRA, Marina A.; RAMOS, Marcus F. K. P.; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; RIBEIRO, UlyssesBackground and ObjectivesThe role of inflammation in cancer development is a well-known phenomenon that may be represented by the neutrophil-lymphocyte ratio (NLR). The present research intends to determine the impact of NLR on the survival outcome of patients with gastric cancer (GC), and to evaluate its use as a stratification factor for the staging groups. MethodsData regarding clinical characteristics, surgery, pathology, and follow-up were retrospectively collected from our single-center prospective database. Blood samples were obtained before surgery. ResultsA total of 383 patients (231 males) who underwent gastrectomy with lymphadenectomy were evaluated between 2009 and 2016. NLR established cutoff was 2.44, and patients were divided in NLR 2.44 (hNLR) and <2.44 (lNLR). hNLR patients (38.4% of the cases) had lower disease-free survival and overall survival (OS) compared to lNLR patients (P=0.047 and P=0.045, respectively). Risk stratification according to NLR value was done in same tumor depth (T4 and
- Gastrectomy for elderly gastric cancer patients: A propensity score-matching analysis(2022) DIAS, Andre R.; PEREIRA, Marina A.; RAMOS, Marcus F. K. P.; BARCHI, Leandro C.; JR, Ulysses Ribeiro; ZILBERSTEIN, Bruno; NAHAS, Sergio C.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.
- Multivisceral resection compared to standard gastrectomy for gastric adenocarcinoma: A propensity score-matching analysis(2022) DIAS, Andre Roncon; PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; JR, Ulysses Ribeiro; ZILBERSTEIN, Bruno; NAHAS, Sergio CarlosBackground 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.