LEONARDO CARDILI

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6
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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 27
  • article 9 Citação(ões) na Scopus
    SclerosingTSC1mutated renal cell carcinoma: An unusual pattern mimickingMITFfamily translocation renal cell carcinoma
    (2020) WILLIAMSON, Sean R.; CARDILI, Leonardo; WHITELEY, Lisa J.; SANCHEZ, Jessica; KIS, Olena
    The tuberous sclerosis genes andMTORare increasingly being found to have important roles in novel subtypes of renal cancer, particularly emerging entities eosinophilic solid and cystic renal cell carcinoma (RCC) and high-grade oncocytic renal tumor (HOT)/RCC with eosinophilic and vacuolated cytoplasm. We report a unique renal neoplasm in a 66-year-old woman that initially mimicked MITF family translocation RCC due to mixed clear and eosinophilic cells, extensive stromal hyalinization, and psammoma bodies, yet which was negative forTFE3andTFEBfluorescence in situ hybridization and a next generation sequencing (NGS) gene fusion assay. Cytoplasmic stippling triggered consideration of TSC-associated neoplasms, and a targeted NGS assay revealed a variant in exon 21 ofTSC1resulting in c.2626G>T p.(Glu876*) truncating mutation. This report adds to the morphologic spectrum of TSC-related renal neoplasms, including prominent stromal hyalinization as a potentially deceptive pattern. Due to the overlap in cytoplasmic stippling between eosinophilic solid and cystic RCC and HOT/RCC with eosinophilic and vacuolated cytoplasm, it is debatable which category this example would best fit. Further understanding of these entities and other renal neoplasms with alterations in the TSC genes will elucidate whether they should be considered a family of tumors.
  • article 1 Citação(ões) na Scopus
    GASTRIC CANCER WITH POSITIVE EXPRESSION OF ESTROGEN RECEPTOR ALPHA: A CASE SERIES FROM A SINGLE WESTERN CENTER
    (2021) SILVA, Alice Cristina Castro D. A.; PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; CARDIL, Leonardo; RIBEIRO JR., Ulysses; ZILBERSTEIN, Bruno; MELLO, Evandro Sobroza de; CASTRIA, Tiago Biachi de
    BACKGROUND: Despite advances in therapies, the prognosis of patients with advanced gastric cancer (GC) remains poor. Several studies have demonstrated the expression of estrogen receptor alpha (ERa); however, its significance in GC remains controversial. AIM: The present study aims to report a case series of GC with ERa-positive expression and describe their clinicopathological characteristics and prognosis. METHODS: We retrospectively evaluated patients with GC who underwent gastrectomy with curative intent between 2009 and 2019. ERa expression was assessed by immunohistochemistry through tissue microarray construction. Patients with ERa-negative gastric adenocarcinoma served as a comparison group. RESULTS: During the selected period, 6 (1.8%) ERa-positive GC were identified among the 345 GC patients analyzed. All ERa-positive patients were men, aged 34-78 years, and had Lauren diffuse GC and pN+ status. Compared with ERa-negative patients, ERa-positive patients had larger tumor size (p=0.031), total gastrectomy (p=0.012), diffuse/mixed Lauren type (p=0.012), presence of perineural invasion (p=0.030), and lymph node metastasis (p=0.215). The final stage was IIA in one case, IIIA in three cases, and IIIB in two cases. Among the six ERa-positive patients, three had disease recurrence (peritoneal) and died. There was no significant difference in survival between ERa-positive and ERa-negative groups. CONCLUSIONS: ERa expression is less common in GC, is associated with diffuse histology and presence of lymph node metastasis, and may be a marker related to tumor progression and worse prognosis. Also, a high rate of peritoneal recurrence was observed in ERa-positive patients. HEADINGS: Stomach Neoplasms. Estrogen Receptor alpha. Immunohistochemistry. Molecular Targeted Therapy. Prognosis
  • article 0 Citação(ões) na Scopus
    Scoring system for prediction of overall survival in patients with renal cell carcinoma T3aN0M0
    (2024) SUARTZ, Caio Vinicius; CORDEIRO, Mauricio Dener; CARVALHO, Paulo Afonso de; GALLUCCI, Fabio Pescarmona; RIBEIRO-FILHO, Leopoldo Alves; CARDILI, Leonardo; SIVARAMAN, Arjun; AUDENET, Francois; MOTA, Jose Mauricio; NAHAS, William Carlos
    ObjectiveWe aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma.MethodsWe reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical-pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan-Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy.ResultsWe analyzed 362 patients classified as pT3aN0M0 stage with a median follow-up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time-dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma.ConclusionPatients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow-up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy.
  • article 1 Citação(ões) na Scopus
    Immunoexpression of BAP1, ROS1, and ALK in Spitzoid Melanocytic Tumors
    (2018) CARDILI, Leonardo; VIANA, Cristiano Ribeiro; GERMANO, Andressa; FERNANDES, Mariana; BARCELLOS, Denise; LANDMAN, Gilles
    Background. Spitzoid tumors are a heterogeneous group of melanocytic neoplasms that frequently imposes diagnostic difficulties. Lately, several advances in molecular biology afforded significant discoveries on the pathogenesis of these tumors. BAP1 (BRCA-1 associated protein-1) inactivation and anomalous expression of kinase translocation-related proteins are among the main criteria launched by new classification proposals. Our aim was to systematically assess the immunoexpression of BAP1, ROS1 (receptor tyrosine kinase c-Ros oncogene 1), and ALK (anaplastic lymphoma receptor tyrosine kinase) proteins in an unpublished series of spitzoid tumors. Methods. Retrospective study based on 47 formalin-fixed paraffin-embedded tissue samples from 3 different institutions. BAP1, ROS1, and ALK immunostains were performed in all cases. We included 27 Spitz tumors without significant abnormality, 15 atypical spitzoid tumors, and 5 spitzoid melanomas. Results. We observed loss of BAP1 nuclear immunolabeling in 4.3% of evaluable cases (2/46), both of them atypical spitzoid tumors. The proportional frequency of BAP1-inactivated cases among atypical spitzoid tumors was 14.2% (2/14). No immunoexpression of ROS1 or ALK was found. Conclusions. Our study revealed 2 additional BAP1-inactived cases and described its respective frequency. The absence of anomalous expression of translocation-related proteins ALK and ROS1 in this series, composed predominantly of low-grade/low-risk tumors, indicates that translocated spitzoid lesions may not be as prevalent as initially suggested, at least in some populations. Furthermore, our findings encourage additional investigation on unequal occurrence of such immunomarkers among different diagnostic categories of spitzoid neoplasms.
  • article 13 Citação(ões) na Scopus
    A Prospective, Randomized Trial Comparing the Outcomes of Open vs Laparoscopic Partial Nephrectomy
    (2022) GUGLIELMETTI, Giuliano B.; ANJOS, Gabriel C. dos; SAWCZYN, Guilherme; RODRIGUES, Gilberto; CARDILI, Leonardo; CORDEIRO, Mauri Prime Cio D.; NEVES, Luiz C. O.; PONTES JUNIOR, Jose; FAZOLI, Arnaldo; COELHO, Rafael F.; SROUGI, Miguel; NAHAS, William C.
    Purpose: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. Materials and Methods: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. Results: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). Conclusions: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.
  • conferenceObject
    Randomized phase II trial of neoadjuvant androgen deprivation therapy plus abiraterone and apalutamide for patients with high-risk localized prostate cancer: Pathologic response and PSMA imaging correlates.
    (2022) BASTOS, Diogo Assed; COELHO, Rafael; CARDILI, Leonardo; GALIZA, Felipe; ILARIO, Eder Nisi; VIANA, Ublio; MURTA, Claudio Bovolenta; GUGLIELMETTI, Giuliano; CORDEIRO, Mauricio; PONTES JR., Jose; MUNIZ, David Queiroz Borges; SILVA, Jamile Almeida; MOTA, Jose Mauricio; FREITAS, Guilherme Fialho De; LEITE, Katia Ramos Moreira; BUCHPIGUEL, Carlos Alberto; NAHAS, William Carlos
  • conferenceObject
    PD-L1 Expression in Gastric Cancer: Correlation Between the Primary Site and Metastatic Lymph Node
    (2021) COIMBRA, Brendha C.; PEREIRA, Marina A.; CARDILI, Leonardo; RAMOS, Marcus Fernando Kodama P.
  • article 1 Citação(ões) na Scopus
    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 Ribeiro
    Background 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.
  • article
    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 Ribeiro
    Objective: 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.
  • article 6 Citação(ões) na Scopus
    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 de
    Background 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.