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
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- A case report of diffuse hyperplastic gastropathy with multiple polypoid formations in a patient with pernicious anemia, Helicobacter pylori infection, hypergastrinemia and hypoalbuminaemia: Do not forget of Menetrier's disease(2020) WAISBERG, Daniel Reis; MELLO, Evandro Sobroza de; TUSTUMI, Francisco; SZOR, Daniel Jose; CHARRUF, Amir Zeide; FUHRO, Felipe Emanuel; WAISBERG, Jaques; DIAS, Andre RonconINTRODUCTION: Menetrier's disease is a rare condition, frequently associated with Helicobacter pylori infection, hypergastrinemia and hypoalbuminaemia. PRESENTATION OF THE CASE: A case of a 55 years-old female patient with a previous diagnosis of pernicious anemia complaining of epigastric discomfort, hyporexia, vomiting, and weight loss is reported. Endoscopy showed multiple gastric polyploid formations and Helicobacter pylori infection was detected. Laboratory tests showed elevated gastrin serum levels and presence of antibodies antiparietal cells, as well as microcytic hypochromic anemia compatible with chronic iron deficiency. Albumin serum level was slightly decreased. Full thickness biopsy performed via echoendoscopy reported gastritis cystica/polyposa profunda. Given the association of diffuse involvement of the entire stomach, the possibility of developing malignant disease and the clinical symptoms, the patient underwent laparoscopic total gastrectomy with Roux-en-Y reconstruction. The surgical specimen showed the mucosa hyperemic and swollen, with prominent gastric folds. Hyperplastic elongation of gastric foveolas associated with disappearance of oxyntic glands was compatible with Menetrier's disease. DISCUSSION: The Menetrier's disease diagnosis may be tricky, especially when an unusual endoscopic presentation is associated with other conditions that may mislead the diagnostic evaluation. The differential diagnoses were gastric malignancies, Zollinger-Ellison syndrome, massive gastric polyposis and gastritis cystica/polyposa proftaida. CONCLUSION: Clinical, laboratory, endoscopic and histopathological findings are paramount for reaching the diagnosis of Menetrier's disease, but it should be suspected in all cases of upper gastrointestinal symptoms and hypertrophied gastric mucosa. (C) 2020 The Authors.
- Incidentally Detected Small Cell Transformation in a Patient With Resected Oligometastatic EGFR- Mutated Cancer Treated With Osimertinib(2020) TEIXEIRA, Carlos Henrique A.; MELLO, Evandro S. de; YEN, Cheng Tzu; HANRIOT, Rodrigo de Morais; YOUNES, Riad Naim
conferenceObject Immunohistochemical Scores for Programmed Death Ligand-1 (PD-L1) Expression and Prognostic in Patients with Gastric Cancer(2020) PEREIRA, Marina A.; RAMOS, Marcus Fernando Kodama P.; RIBEIRO, Renan Ribeiro e; DIAS, Andre R.; RIBEIRO JR., Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; MELLO, Evandro Sobroza; CASTRIA, Tiago B.- Genomic Biomarkers and Underlying Mechanism of Benefit from BCG Immunotherapy in Non-Muscle Invasive Bladder Cancer(2020) BASTOS, Diogo A.; MATTEDI, Romulo L.; BARREIRO, Rodrigo; SANTOS, Filipe F. dos; BUZATTO, Vanessa; MASOTTI, Cibele; SOUZA, Jussara M.; LIMA, Mariana Z. T. de; FRIGUGLIETTI, Giulia W.; DZIK, Carlos; JARDIM, Denis L. F.; COELHO, Rafael; RIBEIRO FILHO, Leopoldo A.; CORDEIRO, Mauricio D.; NAHAS, William C.; MELLO, Evandro S. de; CHAMMAS, Roger; REIS, Luiz Fernando L.; BETTONI, Fabiana; GALANTE, Pedro A. F.; CAMARGO, Anamaria A.BACKGROUND: Optimal therapy for high-risk non-muscle invasive bladder cancer (NMIBC) includes intravesical instillation of Bacillus Calmette-Guerin (BCG). However, about 25-45% of patients do not benefit from BCG immunotherapy, and there is no biomarker to guide therapy. Also, many questions regarding BCG mechanisms of action remain unanswered. OBJECTIVE: To identify genomic biomarkers and characterize the underlying mechanism of benefit from BCG in NMIBC. PATIENTS AND METHODS: Pre-treatment archival index-tumors of 35 patients with NMIBC treated with BCG were analyzed by whole-exome sequencing (WES). Tumor mutation burden (TMB) and neoantigen load (NAL) were correlated with BCG response rate (RR) and recurrence-free survival (RFS). The presence of deleterious mutations in DNA damage response (DDR) genes was also compared between BCG-responsive (BCG-R, N= 17) and unresponsive (BCG-UR, N= 18) subgroups. RESULTS: TMB and NAL were higher in BCG-R compared to BCG-UR patients (median TMB 4.9 vs. 2.8 mutations/Mb, P = 0.017 and median NAL 100 vs. 65 neoantigens, P = 0.032). Improved RR and RFS were observed in patients with high vs. low TMB (RR 71% vs. 28%, P = 0.011 and mRFS 38.0 vs. 15.0 months, P = 0.009) and with high vs. low NAL (RR 71% vs. 28%, P = 0.011 and mRFS 36.0 vs. 18.5 months, P = 0.016). The presence of deleterious mutations in DDR genes was associated with improved RFS (mRFS 35.5 vs. 11.0 months, P = 0.017). CONCLUSIONS: In our cohort, improved outcomes after BCG immunotherapy were observed in patients with high TMB, high NAL and deleterious mutations in DDR genes. BCG may induce tumor-specific immune response by enhancing the recognition of neoantigens.
- Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of gastric cancer(2020) PEIXOTO, Renata D'Alpino; ROCHA-FILHO, Duilio R.; WESCHENFELDER, Rui F.; REGO, Juliana F. M.; RIECHELMANN, Rachel; COUTINHO, Anelisa K.; FERNANDES, Gustavo S.; JACOME, Alexandre A.; ANDRADE, Aline C.; MURAD, Andre M.; MELLO, Celso A. L.; MIGUEL, Diego S. C. G.; GOMES, Diogo B. D.; RACY, Douglas J.; MORAES, Eduardo D.; AKAISHI, Eduardo H.; CARVALHO, Elisangela S.; MELLO, Evandro S.; MALUF FILHO, Fauze; COIMBRA, Felipe J. F.; CAPARELI, Fernanda C.; ARRUDA, Fernando F.; VIEIRA, Fernando M. A. C.; TAKEDA, Flavio R.; COTTI, Guilherme C. C.; PEREIRA, Guilherme L. S.; PAULO, Gustavo A.; RIBEIRO, Heber S. C.; LOURENCO, Laercio G.; CROSARA, Marcela; TONETO, Marcelo G.; OLIVEIRA, Marcos B.; OLIVEIRA, Maria de Lourdes; BEGNAMI, Maria Dirlei; FORONES, Nora M.; YAGI, Osmar; ASHTON-PROLLA, Patricia; AGUILLAR, Patricia B.; AMARAL, Paulo C. G.; HOFF, Paulo M.; ARAUJO, Raphael L. C.; PAULA FILHO, Raphael P. Di; GANSL, Rene C.; GIL, Roberto A.; PFIFFER, Tulio E. F.; SOUZA, Tulio; JR, Ulysses Ribeiro; JESUS, Victor Hugo F.; JR, Wilson L. Costa; PROLLA, GabrielGastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.
- 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, IvanPurpose 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.
conferenceObject Retrospective analysis of intraoperative radiation therapy with low-kilovoltage x-rays (IORT-LK) in soft tissue sarcomas (STS).(2020) DAVID, Waldec Jorge; HANRIOT, Rodrigo De Morais; PAULA FILHO, Raphael Paulo Di; SILVA, Pedro Alexandre Ismael Amaral; COSTA, Marcos Andre De Sa Barreto; YEN, Cheng Tzu; MELLO, Evandro Sobroza de- Cancer-associated fibroblast regulation by microRNAs promotes invasion of oral squamous cell carcinoma(2020) MATOS, Leandro Luongo; MENDERICO JUNIOR, Gilberto Mendes; THEODORO, Therese Rachell; PASINI, Fatima Solange; ISHIKAWA, Marina de Menezes; RIBEIRO, Andromeda Aryane Bomtempo; MELLO, Evandro Sobroza de; PINHAL, Maria Aparecida da Silva; MOYSES, Raquel Ajub; KULCSAR, Marco Aurelio Vamondes; DEDIVITIS, Rogerio Aparecido; CERNEA, Claudio Roberto; KOWALSKI, Luiz PauloThe objective of the present study was to evaluate the role of microRNA-mediated remodeling of the extracellular matrix in the process of tumor invasion of oral squamous cell carcinoma and to evaluate its relationship with the prognosis of these patients. This was a retrospective study on material from the paraffin blocks of patients operated on for oral squamous cell carcinoma, in addition to a group of healthy oral mucosa samples of paired patients. miR-1-3p, miR-133-3p, and miR-21-5p were differentially expressed between the superficial and deep tumor groups. miR-21-5p was the one with the greatest accuracy in the differentiation between superficial and deep tumors. By immunohistochemistry, the group of deep tumors showed greater immunoreactivity to matrix metalloproteinases 2 and 9 and laminin a in tumor-associated fibroblasts, with consequent degradation of the basal membrane, measured by greater loss of continuity of type IV collagen. This process was also associated with lower and higher expression of miR-1-3p and miR-21-5p, respectively. There was also a trend toward better overall and disease-free survival rates in patients with higher miR-133a-3p. The present study showed the interaction between microRNAs and extracellular matrix remodeling in oral squamous cell carcinoma.
conferenceObject Remnant Gastric Cancer: Neglect Group with High Potential for Immunotherapy(2020) RAMOS, Marcus Fernando Kodama P.; PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi; RIBEIRO, Renan Ribeiro e; MELLO, Evandro Sobroza; DIAS, Andre Roncon; ZILBERSTEIN, Bruno; RIBEIRO JR., Ulysses; CECCONELLO, Ivan- Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?(2020) RAMOS, Marcus F. K. P.; PEREIRA, Marina A.; AMORIM, Larissa C.; MELLO, Evandro S. de; FARAJ, Sheila F.; JR, Ulysses Ribeiro; HOFF, Paulo M. G.; CECCONELLO, Ivan; CASTRIA, Tiago B. deBackground Gastric cancer (GC) has been defined in distinct molecular subtypes with different therapeutic implications. However, its clinical significance and prognosis regarding standard chemotherapy (CMT) remains unclear. This study aimed to analyze the impact of perioperative or adjuvant treatment among subtypes of GC. Methods We retrospectively evaluated all stage II/III patients with GC who underwent a curative gastrectomy. Based on immunohistochemistry and in situ hybridization techniques, GC was classified into five subtypes: Epstein-Barr virus (EBV) positive, microsatellite instability (MSI), e-cadherin aberrant, p53-aberrant, and p53-normal. Results Among the 178 CG included, 111 patients received CMT and 67 were treated with surgery alone. Survival analysis showed that p53-aberrant GC treated with CMT had better disease-free survival (DFS) compared with surgery alone (P = .001).There was no significant difference in DFS between patients who received CMT and those with surgery alone for EBV, MSI, E-cadherin, and p53-normal GC. An improvement in overall survival was observed only for E-cadherin (P = .001) and p53-aberrant (P < .001) patients who received CMT. Conclusions CMT showed different impact on the survival of CG according to the molecular subtype. No survival benefit was observed for EBV and MSI groups who received CMT. GC with p53-aberrant had a significant benefit in survival with standard therapy.