EVANDRO SOBROZA DE MELLO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Lymph Node Yield After Neoadjuvant Chemoradiotherapy in Rectal Cancer Specimens: A Randomized Trial Comparing Two Fixatives(2018) DIAS, Andre R.; PEREIRA, Marina Alessandra; MELLO, Evandro Sobroza de; NAHAS, Sergio Carlos; CECCONELLO, Ivan; RIBEIRO JR., UlyssesBACKGROUND: It is widely reported that neoadjuvant chemoradiation reduces lymph node yield in rectal cancer specimens. Some have questioned the adequacy of finding 12 lymph nodes for accurate staging, and fewer nodes were correlated with good response. Others reported that low lymph node count raises the chance for understaging and correlates with worse survival. In addition, a few studies demonstrated that diligent specimen analysis increases lymph node count. OBJECTIVE: The aim of this study was to compare Carnoy's solution and formalin concerning lymph node yield in specimens of patients with rectal cancer after neoadjuvant chemoradiation. DESIGN: This is a prospective randomized trial that was conducted from 2012 to 2015. SETTINGS: This study was performed in a reference cancer center in Brazil. PATIENTS: Patients who underwent low anterior resection with total mesorectal excision after neoadjuvant chemoradiation for rectal adenocarcinoma were included. INTERVENTION: Rectosigmoid specimens were randomized for fixation with Carnoy's solution or formalin. MAIN OUTCOME MEASURES: A total of 130 specimens were randomized. After dissection, the residual fat from the formalin group was immersed in Carnoy's solution in search for missed lymph nodes (Revision). RESULTS: The Carnoy's solution group had superior lymph node count (24.0 vs 16.3, p < 0.01) and fewer cases with <12 lymph nodes (6 vs 22, p = 0.001). The Revision group found lymph nodes in all cases (mean, 11.1), retrieving metastatic lymph nodes in 6 patients. It reduced the formalin cases with <12 lymph nodes from 33.8% to 4.6% and upstaged 2 patients. Tumor response to neoadjuvant chemoradiotherapy was not associated with lymph node count. LIMITATIONS: This was a unicentric study. CONCLUSIONS: Compared with formalin, the Carnoy's solution increases lymph node count and reduces the cases with <12 lymph nodes. Harvested lymph nodes are missed following routine analysis and this is clinically relevant. Finding <12 lymph nodes is not a sign of good response to neoadjuvant chemoradiation (www.clinicaltrials.gov. Unique identifier: NCT02629315). See Video Abstract at http://links.lww.com/DCR/A694.
- Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases(2018) FONSECA, Gilton M.; MELLO, Evandro S. de; FARAJ, Sheila F.; KRUGER, Jaime A. P.; COELHO, Fabricio F.; JEISMANN, Vagner B.; LUPINACCI, Renato M.; CECCONELLO, Ivan; ALVES, Venancio A. F.; PAWLIK, Timothy M.; HERMAN, PauloBackgroundHistomorphological features have been described as prognostic factors after resection of colorectal liver metastases (CLM). The objectives of this study were to assess the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDC) among CLM, and their association with other prognostic factors. MethodsWe evaluated 229 patients who underwent a first resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory infiltrate. Lymphatic and portal invasion were evaluated through D2-40 and CD34 antibody. ResultsFactors independently associated with poor overall survival were nodules>4 (P=0.002), presence of PDC G3 (P=0.007), portal invasion (P=0.005), and absence of tumor pseudocapsule (P=0.006). Factors independently associated with disease-free survival included number of nodules>4 (P<0.001), presence of PDC G3 (P=0.005), infiltrative border (P=0.031), portal invasion (P=0.006), and absent/mild peritumoral inflammatory infiltrate (P=0.002). PDC and TB were also associated with histological factors, as portal invasion (TB), peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of tumor pseudocapsule (TB and PDC). ConclusionsThis is the first study demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor, but it was not an independent predictor of survival.
- Hepatic granulomas: Differential diagnosis(2018) MELLO, E. S. de; ALVES, V. A. Ferreira
- Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma(2018) DANILOVIC, Debora Lucia Seguro; MELLO, Evandro Sobroza de; FRAZZATO, Eliana Salgado Turri; WAKAMATSU, Alda; JORGE, Alexander Augusto de Lima; HOFF, Ana Oliveira; MARUI, SuemiBackgroundNuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. MethodsCoding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. ResultsAlthough no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. ConclusionWe identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences.
- 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.
- 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.
- Pathologic complete response implies a fewer number of lymph nodes in specimen of rectal cancer patients treated by neoadjuvant therapy and total mesorectal excision(2018) BUSTAMANTE-LOPEZ, Leonardo Alfonso; NAHAS, Caio Sergio Rizkallah; NAHAS, Sergio Carlos; MARQUES, Carlos Frederico Sparapan; PINTO, Rodrigo Ambar; COTTI, Guilherme Cutait; IMPERIALE, Antonio Rocco; MELLO, Evandro Sobroza de; RIBEIRO JUNIOR, Ulysses; CECCONELLO, IvanStudies have suggested that the use of neoadjuvant chemoradiation results in a lower lymph nodes yield in rectal cancer patients. Objective: To evaluate factors associated with less than 12 lymph nodes harvested on patients with rectal cancer treated with preoperative chemoradiotherapy followed by total mesorectal excision. Patients: This was a cohort/retrospective single cancer center study. Low and mid locally advanced rectal cancer or T2N0 under risk of sphincter resection underwent chemoradiotherapy followed by total mesorectal excision with curative intent. Chemotherapy consisted of 5-FU and leucovorin IV. Total dose of pelvic radiation was 5040 Gys. All patients were staged and restaged by digital rectal examination, proctoscopy, colonoscopy, CT of abdomen and chest, and MRI of the pelvis. Patients were stratified in two groups: >= 12 and < 12 L N retrieved. The possible factors affecting number of LN were analyzed. Results: 95 patients ma the inclusion criteria. Mean LN harvest was 23.2 (3-67). 81 patients (85%) had >= 12 L N. Gender, age, tumor size, tumor stage, tumor location, length of specimen, presence of LN involvement, type of surgery, and surgical access showed no association with number of LN retrieved. Only pathological complete response showed a statistically significant association with < 12 L N on univariate (p = 0.004) and multivariate analyses (p = 0.002). Limitations: Data were collected retrospectively. The number of patients disparity between the two groups. Conclusions: Complete pathologic response is associated with < 12 L N harvested. Thus, the number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection in patients with pathologic complete response.
conferenceObject VALIDATION OF EXPANDED ENDOSCOPIC SUBMUCOSAL DISSECTION CRITERIA FOR TREATMENT OF EARLY GASTRIC ADENOCARCINOMA IN A WESTERN CENTER(2018) PESSORRUSSO, Fernanda C.; FELIPE-SILVA, Aloisio; JACOB, Carlos E.; RAMOS, Marcus F.; ZILBERSTEIN, Bruno; ALVES, Venancio A.; MELLO, Evandro S.; PEREIRA, Marina; CECCONELLO, Ivan; RIBEIRO, Ulysses; MALUF-FILHO, Fauze- Reply to ""Poorly differentiated clusters in colorectal liver metastases: Prognostic significance in synchronous and metachronous metastases""(2018) FONSECA, Gilton M.; MELLO, Evandro S. de; COELHO, Fabricio F.; KRUGER, Jaime A. P.; FARAJ, Sheila F.; JEISMANN, Vagner B.; PAWLIK, Timothy M.; HERMAN, Paulo
- Risk Factors for Lymph Node Metastasis in Western Early Gastric Cancer After Optimal Surgical Treatment(2018) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; FARAJ, Sheila Friedrich; YAGI, Osmar Kenji; SAFATLE-RIBEIRO, Adriana Vaz; MALUF-FILHO, Fauze; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; MELLO, Evandro Sobroza de; RIBEIRO JR., UlyssesLymph node metastasis (LNM) has a strong influence on the prognosis of patients with early gastric cancer (EGC). As minimally invasive treatments are considered appropriate for EGC, and lymphadenectomy may be restricted or even eliminated in some cases; it is imperative to identify the main risk factors for LNM to individualize the therapeutic approach. This study aims to evaluate the risk factors for LNM in EGC and to determine the adequacy of the endoscopic resection criteria in a western population. EGC patients who underwent gastrectomy with lymphadenectomy were retrospectively analyzed utilizing a prospective database. The clinicopathological variables were assessed to determine which factors were associated to LNM. Among 474 enrolled patients, 105 had EGC (22.1%). LNM occurred in 13.3% of all EGC (10% T1a; 15.4% T1b). Tumor size, venous, lymphatic, and perineural invasions were confirmed as independent predictors of LNM by multivariate analysis. Expanded criteria were safely adopted only in selected cases, and 13.6% of patients who matched expanded indication had LNM. Tumor size, venous, lymphatic, and perineural invasions were associated with LNM and should be considered as surrogate markers for surgical treatment of EGC. Expanded criteria for endoscopic resection can be safely adopted only in selected cases.