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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- 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.
- 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
- 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.
- 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.
- Searching for SARS-CoV-2 in Cancer Tissues: Results of an Extensive Methodologic Approach based on ACE2 and Furin Expression(2022) RICARDO, Sara; CANAO, Pedro; MARTINS, Diana; MAGALHAES, Ana C.; PEREIRA, Marina; RIBEIRO-JUNIOR, Ulysses; MELLO, Evandro Sobroza de; ALVES, Venancio A.; PINTO, Regina; LEITAO, Dina; ALVES, Georgina; OLIVEIRA, Rute; WILTON, Joana; COSTELHA, Susete; MEIRELES, Diana; CABANES, Didier; DAVID, Leonor; SCHMITT, FernandoSimple Summary SARS-CoV-2 is the virus that causes COVD-19; there is consensus that this virus infects cells presenting the angiotensin-converting enzyme 2 (ACE2) receptor at the cell surface. In our study, we assessed the expression profiles of cancer cells regarding the expressions of ACE2 and furin (another important player in the infection process). We analyzed a series of formalin-fixed paraffin-embedded samples of tumor tissues from cancer patients who underwent surgery at the beginning of the pandemic, including some cases with known positive results for SARS-CoV-2. Our goal was to explore the possibility of viral infections in cancer tissues by detecting viral RNA and/or proteins using histology-based methods. From this extensive methodologic approach, we show that colon and gastric carcinoma cells present high expression levels of ACE2 and furin, contrasting with a negative expression profile of ACE2 in thyroid carcinoma. Some cases tested positive for SARS-CoV-2 by PCR extracted from tissue sections, but in situ hybridization and immunohistochemistry did not show consistent results of a viral presence in the cancer cells. Our study raises the possibility of ACE2-mediated viral tropism for cancer tissues to be clarified in future studies. SARS-CoV-2 pandemics have been massively characterized on a global scale by the rapid generation of in-depth genomic information. The main entry gate of SARS-CoV-2 in human cells is the angiotensin-converting enzyme 2 (ACE2) receptor. The expression of this protein has been reported in several human tissues, suggesting a correlation between SARS-CoV-2 organotropism and ACE2 distribution. In this study, we selected (a series of) 90 patients who were submitted to surgery for tumor removal between the beginning of the SARS-CoV-2 pandemic and the closure of operating rooms (by the end of March 2020) in two different countries-Portugal and Brazil. We evaluated the expressions of ACE2 and furin (another important factor for virus internalization) in colon (n = 60), gastric (n = 19), and thyroid (n = 11) carcinomas. In a subseries of cases with PCR results for SARS-CoV-2 detection in the peri-operatory window (n = 18), we performed different methodological approaches for viral detections in patient tumor samples. Our results show that colon and gastric carcinomas display favorable microenvironments to SARS-CoV-2 tropism, presenting high expression levels of ACE2 and furin. From the subseries of 18 cases, 11 tested positive via PCR detection performed in tumor blocks; however, a direct association between the ACE2 expression and SARS-CoV-2 infection was not demonstrated in cancer cells using histology-based techniques, such as immunohistochemistry or in situ hybridization. This study raises the possibility of ACE2-mediated viral tropism in cancer tissues to be clarified in future studies.
- 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.
- Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence(2022) FONSECA, Leonardo G. Da; HASHIZUME, Pedro H.; OLIVEIRA, Irai Santana de; IZQUIERDO-SANCHEZ, Laura; SAUD, Lisa Rodrigues da Cunha; XERFAN, Mariana Pinheiro; ALVES, Venancio Avancini Ferreira; MELLO, Evandro Sobroza de; HERMAN, Paulo; BANALES, Jesus M.; OLIVEIRA, Claudia P.; CARRILHO, Flair J.Simple Summary A potential relationship between cholangiocarcinoma and metabolic disorders has been suggested, but there is a lack of published data. This study aimed to describe the prevalence of metabolic disorders in a cohort of 122 patients with cholangiocarcinoma and report clinical outcomes. We found a prevalence of 42.6% of metabolic disorders. There was no significant difference in overall survival between patients with or without metabolic disorders, although there was a better survival in the subgroup of patients undergoing surgical resection. This indicates a need to better explore the association between cholangiocarcinoma in a metabolic background. Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (""metabolic disorder group"") and (2) without any of these features (""non-metabolic-disorder group""). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1-17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The ""metabolic disorder group"" (n = 52) had a median survival of 15.5 months (95% CI 10.9-33.9) vs. 11.5 months (95% CI 8.4-16.5) in the ""non-metabolic-disorder group"" (n = 70) (HR: 1.10; 95% CI 0.62-1.94). Patients with resectable disease in the ""metabolic group"" had longer survival than patients in the ""non-metabolic group"" (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6-26.9); HR = 0.12, 95% CI 0.03-0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background.
- Biochemical and molecular characterization of thyroid tissue by micro-Raman spectroscopy and gene expression analysis(2016) NETO, Lazaro P. M.; MARTIN, Airton A.; SOTO, Claudio A. T.; SANTOS, Andre B.; MELLO, Evandro S.; PEREIRA, Marina A.; CERNEA, Claudio R.; BRANDAO, Lenine G.; CANEVARI, Renata A.Thyroid carcinomas represent the main endocrine malignancy and their diagnosis may produce inconclusive results. Raman spectroscopy and gene expression analysis have shown excellent results on the differentiation of carcinomas. This study aimed to improve the discrimination between different thyroid pathologies combining of both analyses. A total of 35 thyroid tissues samples including normal tissue (n= 10), goiter (n= 10), papillary (n= 10) and follicular carcinomas (n= 5) were analyzed. Confocal Raman spectra was obtain by using a Rivers Diagnostic System, 785 nm laser excitation and CCD detector. The data was processed by the software Labspec5 and Origin 8.5 and analyzed by Minitab (R) program. The gene expression analysis was performed by qRT-PCR technique for TG, TPO, PDGFB, SERPINA1, LGALS3 and TFF3 genes and statistically analyzed by Mann-Whitney test. The confocal Raman spectroscopy allowed a maximum discrimination of 91.1% between normal and tumor tissues, 84.8% between benign and malignant pathologies and 84.6% among carcinomas analyzed. Significant differences was observed for TG, LGALS3, SERPINA1 and TFF3 genes between benign lesions and carcinomas, and SERPINA1 and TFF3 genes between papillary and follicular carcinomas. Principal component analysis was performed using PC1 and PC2 in the papillary carcinoma samples that showed over gene expression when compared with normal sample, where 90% of discrimination was observed at the Amide 1 (1655 cm(-1)), and at the tyrosine spectra region (856 cm(-1)). The discrimination of tissues thyroid carried out by confocal Raman spectroscopy and gene expression analysis indicate that these techniques are promising tools to be used in the diagnosis of thyroid lesions.