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
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Prognostic Role of Neutrophil/Lymphocyte Ratio in Resected Gastric Cancer: A Systematic Review and Meta-analysis(2018) SZOR, Daniel Jose; DIAS, Andre Roncon; PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; RIBEIRO-JUNIOR, UlyssesHigh levels of inflammatory markers and the neutrophil-lymphocyte ratio appear to be associated with worse overall survival in solid tumors. However, few studies have analyzed the role of the neutrophil-lymphocyte ratio in gastric cancer patients scheduled to undergo curative resection. In the present study, a systematic review and meta-analysis was performed to analyze the relationship between the neutrophil-lymphocyte ratio and overall survival in patients with gastric cancer submitted to curative resection and to identify the clinicopathological features (age, gender, tumor depth, nodal involvement and tumor differentiation) that are correlated with high neutrophil-lymphocyte ratios. A literature search of PubMed, Scopus, Cochrane and EMBASE through November 2017 was conducted. Articles that included gastric cancer patients submitted to curative resection and preoperatory neutrophil-lymphocyte ratio values were included. A total of 7 studies comprising 3264 patients from 5 different countries were included. The meta-analysis revealed an association of high neutrophil-lymphocyte ratios with older age, male gender, lower 5-year overall survival, increased depth of tumor invasion, positive nodal involvement but not with histological differentiation. Evaluation of the neutrophil-lymphocyte ratio is a cost-effective method that is widely available in preoperatory settings. Furthermore, it can effectively predict prognosis, as high values of this biomarker are related to more aggressive tumor characteristics. This ratio can also be used to stratify risk in patients within the same disease stage and may be used to assist in individualized follow-up and treatment.
- Isolated splenic metastasis from lung squamous cell carcinoma(2012) DIAS, Andre R.; PINTO, Rodrigo A.; RAVANINI, Juliana N.; LUPINACCI, Renato M.; CECCONELLO, Ivan; RIBEIRO JR., UlyssesIsolated splenic metastasis from lung cancer is a very rare occurrence with only a few reports available. Here, we report the case of a 82-year-old male who underwent a bilobectomy for a lung squamous cell carcinoma and 16 months later developed an isolated splenic metastasis. Additionally, previous reports are reviewed and discussed.
- 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.
- 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.
- 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.
- 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, IvanBackground: 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.
- 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