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
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- 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.
- Tumor growth pattern as predictor of colorectal liver metastasis recurrence(2014) PINHEIRO, Rafael S.; HERMAN, Paulo; LUPINACCI, Renato M.; LAI, Quirino; MELLO, Evandro S.; COELHO, Fabricio F.; PERINI, Marcos V.; PUGLIESE, Vincenzo; ANDRAUS, Wellington; CECCONELLO, Ivan; D'ALBUQUERQUE, Luiz CarneiroBACKGROUND: Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence. METHODS: We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing). RESULTS: Tumor recurrence was observed in 65 patients (71.4%). According to multivariate analysis, 3 or more lesions (P = .05) and the infiltrative tumor margin type (P = .05) were unique independent risk factors for recurrence. Patients with infiltrative margins had a 5-year disease-free survival rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P = .05). CONCLUSIONS: CRM patients with pushing margins presented superior disease-free survival rates compared with patients with infiltrative margins. Thus, the adoption of the margin pattern can represent a tool for improved selection of patients for adjuvant treatment.
- Prognostic implication of mucinous histology in resected colorectal cancer liver metastases(2014) LUPINACCI, Renato Micelli; MELLO, Evandro Sobroza; COELHO, Fabricio Ferreira; KRUGER, Jaime Arthur Pirolla; PERINI, Marcos Vinicius; PINHEIRO, Rafael S.; FONSECA, Gilton Marques; CECCONELLO, Ivan; HERMAN, PauloBackground. Colorectal mucinous adenocarcinoma (MAC) is a subtype of colorectal adenocarcinoma with prominent mucin production associated with proximal location of tumor, advanced stage at diagnosis, microsatellite instability, and BRAF mutation. The prognostic implication of MAC in colorectal cancer liver metastases (CRCLM) is unknown. The purpose of our study was to determine the frequency and elucidate the prognostic implication of mucinous histology in CRCLM. Methods. The medical records of 118 patients who underwent CRCLM resection between 2000 and 2010 were reviewed. Clinicopathologic variables and outcome parameters were examined. Resected specimens were submitted to routine histologic evaluation. Patients were grouped according to the metastasis mucinous content: >50%, MAC;.<50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Results. Mean follow-up after resection was 37 months. Tumor recurrence was, observed in 75% of patients. Overall survival and disease-free survival rates after hepatectomy were 61%, 56%, and 26%, 24% at 3 and 5 years, respectively. Tumors with mucinous component (AIM and MAC) were related to proximal location of the primary tumor and were more frequently observed in females. Multivariate analysis revealed that MAC was an independent negative prognostic factor (hazard ratio, 3.13; 95% CI, 1.30-6.68; P = .011) compared with non-MAC (NMA and AIM). Conclusion. MAC has an adverse prognostic impact compared with NMA, which may influence therapeutic strategy raising an important subject for discussion and future investigation.
- Dimensão da margem cirúrgica nas ressecções de metástase hepática de câncer colorretal: impacto na recidiva e sobrevida(2013) HERMAN, Paulo; PINHEIRO, Rafael S.; MELLO, Evandro S.; LAI, Quirino; LUPINACCI, Renato M.; PERINI, Marcos V.; PUGLIESE, Vincenzo; ANDRAUS, Wellington; COELHO, Fabricio F.; CECCONELLO, Ivan; D'ALBUQUERQUE, Luiz C.BACKGROUND: Approximately 50% of the patients with a colorectal tumor develop liver metastasis, for which hepatectomy is the standard care. Several prognostic factors have been discussed, among which is the surgical margin. This is a recurring issue, since no consensus exists as to the minimum required distance between the metastatic nodule and the liver transection line. AIM: To evaluate the surgical margins in liver resections for colorectal metastases and their correlation with local recurrence and survival. METHODS: A retrospective study based on the review of the medical records of 91 patients who underwent resection of liver metastases of colorectal cancer. A histopathological review was performed of all the cases; the smallest surgical margin was verified, and the late outcome of recurrence and survival was evaluated. RESULTS: No statistical difference was found in recurrence rates and overall survival between the patients with negative or positive margins (R0 versus R1); likewise, there was no statistical difference between subcentimeter margins and those greater than 1 cm. The disease-free survival of the patients with microscopically positive margins was significantly worse than that of the patients with negative margins. The uni- and multivariate analyses did not establish the surgical margin (R1, narrow or less than 1 cm) as a risk factor for recurrence. CONCLUSION: The resections of liver metastases with negative margins, independently of the margin width, had no impact on tumor recurrence (intra- or extrahepatic) or patient survival
- Infiltrative Tumor Borders in Colorectal Liver Metastasis: Should We Enlarge Margin Size?(2021) JAYME, Vitoria Ramos; FONSECA, Gilton Marques; AMARAL, Isaac Massaud Amim; COELHO, Fabricio Ferreira; KRUGER, Jaime Arthur Pirola; JEISMANN, Vagner Birk; PINHEIRO, Rafael Soares Nunes; MELLO, Evandro Sobroza de; HERMAN, PauloBackground Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLMs). Despite an improvement in results following resection, recurrence rates remain high. Many histopathological features have been reported as prognostic factors. Infiltrative borders are known to be associated with worse prognosis; however, margin size has never been evaluated together with the type of tumor border. In the present study, we analyzed the prognosis of patients with resected CRLM according to tumor growth pattern (TGP) and whether a larger margin size would bring any prognostic benefit. Patients and Methods Medical records from a prospective database of 645 patients who underwent hepatic resection for CRLM between January 2004 and December 2019 at a single center were reviewed, and 266 patients were included in the analytic cohort. TGP (pushing or infiltrative) was evaluated regarding the impact in overall and disease-free survival. The impact of margin size (<= or > 1 cm) on survival and hepatic recurrence according to TGP was also evaluated. Results TGP was defined as infiltrative in 182 cases (68.4%) and pushing in 84 patients (31.6%). Patients with infiltrative-type border presented worse overall survival and disease-free survival, as well as higher intrahepatic recurrence (p < 0.05). Larger margin size did not impact the prognosis of patients with infiltrative borders. Conclusions Patients with infiltrative-type border present worse prognosis and higher intrahepatic recurrence. Larger margin size (> 1 cm) does not change the prognosis in patients with infiltrative border, showing that tumor biology is the most important factor for survival.
- 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.
- Histopathological factors versus margin size in single colorectal liver metastases: Does a 1-cm margin size matter?(2022) FONSECA, Gilton M.; MELLO, Evandro S. de; FARAJ, Sheila F.; KRUGER, Jaime A. P.; JEISMANN, Vagner B.; COELHO, Fabricio F.; ALVES, Venancio A. F.; HERMAN, PauloBackground and objective: The ideal margin width for surgical resection of colorectal liver metastases has been extensively studied, but not sufficiently in accordance with other pathological factors. The aim of this study was to assess for the first time the prognostic impact of margin widths according to different prognostic pathological factors in colorectal liver metastasis. Methods: We evaluated 101 patients with a single resected metastasis. Slides stained by HE were assessed for the presence of poorly differentiated clusters, peritumoral inflammatory infiltrate, tumor pseudocapsule, and tumor borders pattern. Overall survival, disease-free survival, and hepatic recurrence were evaluated. The pathologic factors prognostic impact was evaluated according to a (< or >) 10-mm margin size. Results: Factors independently associated with a shorter overall survival were absence of tumor pseudocapsule (p < 0.001) and infiltrative tumor border pattern (p = 0.019). The absence of tumor pseudocapsule was the only factor independently associated with shorter disease-free survival (p < 0.001). Hepatic recurrence was associated with infiltrative tumor border and absence of pseudocapsule. Margin width > 10 mm did not impact overall survival independently of the studied histological prognostic factors. Conclusions: In colorectal liver metastasis resection, the absence of tumor pseudocapsule was significantly associated with shorter overall survival and disease-free survival and hepatic recurrence. However, margins larger than 10 mm did not offer survival benefit when other pathologic negative prognostic factors were concomitantly analyzed, reinforcing the idea that biology, rather than margin size, is crucial for prognosis.
- Histopathological prognostic factors for colorectal liver metastases: A systematic review and meta-analysis of observational studies(2021) OLIVEIRA, Cassio Virgilio Cavalcante de; FONSECA, Gilton Marques; KRUGER, Jaime Arthur Pirola; MELLO, Evandro Sobroza de; COELHO, Fabricio Ferreira; HERMAN, PauloIntroduction. Resection is the mainstay of treatment for colorectal liver metastases (CRLMs). Many different histopathological factors related to the primary colorectal tumour have been well studied; however, histopathological prognostic factors related to CRLMs are still under evaluation. Objective. To identify histopathological factors related to overall survival (OS) and disease-free survival (DFS) in patients with resected CRLMs. Methods. A systematic review was performed with the following databases up to August 2020: PubMed, EMBASE, Web of Science, SciELO, and LILACS. The GRADE approach was used to rate the overall certainty of evidence by outcome. Results. Thirty-three studies including 4,641 patients were eligible. We found very low certainty evidence that the following histopathological prognostic factors are associated with a statistically significant decrease in OS: presence of portal vein invasion (HR, 410.50 [95% CI, 0.37 to 0.68]; I-2=0%), presence of perineural invasion (HR, 0.55 [95% CI, 420.36 to 0.83]; I-2=0%), absence of pseudocapsule (HR, 0.41 [CI 95%, 0.29 to 0.57], p<0.00001; I-2=0%), presence of satellite nodules (OR, 0.45 [95% CI, 0.26 to 0.80]; I-2=0%), and the absence of peritumoural inflammatory infiltrate (OR, 0.20 [95% CI, 0.08 to 0.54]; I-2=0%). Outcome data on DFS were scarce, except for tumour borders, which did not present a significant impact, precluding the meta-analysis. Conclusion. Of the histopathological prognostic factors studied, low- to moderate-certainty evidence shows that vascular invasion, perineural invasion, absence of pseudocapsule, presence of satellite nodules, and absence of peritumoral inflammatory infiltrate are associated with shorter overall survival in CRLMs.
- Intrahepatic Lymphatic Invasion but not Vascular Invasion is a Major Prognostic Factor after Resection of Colorectal Cancer Liver Metastases(2014) LUPINACCI, Renato Micelli; MELLO, Evandro Sobrosa; PINHEIRO, Rafael S.; MARQUES, Gilton; COELHO, Fabricio Ferreira; KRUGER, Jaime Arthur Pirolla; PERINI, Marcos Vinicius; HERMAN, PauloDespite advances in diagnosis and surgical strategies, up to 70 % of patients will develop recurrence of the disease after resection of colorectal cancer liver metastases (CRCLM). The purpose of our study was to determine the frequency of four different mechanisms of intrahepatic dissemination, and to evaluate the impact of each mechanism on patient outcomes. The medical records of 118 patients who underwent a first resection of CRCLM during the period between 2000 and 2010 were reviewed. Clinicopathologic variables and outcome parameters were examined. Resected specimens were submitted to routine histological evaluation, and immunohistochemical staining with D2-40 (lymphatic vessels), CD34 (blood vessels), CK-7 (biliary epithelium), and CK-20 (CRC cells). The mean follow-up after resection was 38 months. Tumor recurrence was observed in 76 patients, with a median interval of 13 months after resection. Overall survival and disease-free survival (DFS) rates after hepatectomy were 62 and 56 %, and 26 and 24 % at 3 and 5 years, respectively. Intrahepatic microscopic invasion included portal venous in 49 patients, sinusoidal in 43 patients, biliary in 20 patients, and lymphatic in 33 patients. Intra-hepatic lymphatic invasion was the only mechanism of dissemination independently associated with the risk of hepatic recurrence (odds ratio 2.75) and shorter DFS (p = 0.006). Intrahepatic lymphatic invasion is a significant prognostic factor. Other mechanisms of invasion, although frequently observed, are not related to recurrence or survival, suggesting that the lymphatic system is the main route for dissemination of CRCLM. Furthermore, immunohistochemical detection of intrahepatic lymphatic invasion might be of value in clinical practice.
- 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