LUCIANA OBA ONISHI KIKUCHI

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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

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  • article 21 Citação(ões) na Scopus
    Early Age Hepatocellular Carcinoma Associated With Hepatitis B Infection in South America
    (2017) CHAN, Aaron J.; BALDERRAMO, Domingo; KIKUCHI, Luciana; BALLERGA, Esteban Gonzalez; PRIETO, Jhon E.; TAPIAS, Monica; IDROVO, Victor; DAVALOS, Milagros B.; CAIRO, Fernando; BARREYRO, Fernando J.; PAREDES, Sebastian; HERNANDEZ, Nelia; AVENDANO, Karla; FERRER, Javier Diaz; YANG, Ju Dong; CARRERA, Enrique; MATTOS, Angelo Z.; HIRSCH, Bruno S.; GONCALVES, Pablo T.; CARRILHO, Flair J.; ROBERTS, Lewis R.; DEBES, Jose D.
  • article 25 Citação(ões) na Scopus
    Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases
    (2015) CHAGAS, Aline Lopes; KIKUCHI, Luciana; HERMAN, Paulo; ALENCAR, Regiane S. S. M.; TANI, Claudia M.; DINIZ, Marcio Augusto; PUGLIESE, Vincenzo; ROCHA, Manoel de Souza; D'ALBUQUERQUE, Luiz Augusto Carneiro; CARRILHO, Flair Jose; ALVES, Venancio A. F.
    OBJECTIVES: Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival. METHODS: We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed. RESULTS: The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had ""pure fibrolamellar hepatocellular carcinoma,'' whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having ""mixed fibrolamellar hepatocellular carcinoma.'' The median overall survival was 36 months. The presence of ""mixed fibrolamellar hepatocellular carcinoma'' and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery. CONCLUSION: Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival.
  • article 19 Citação(ões) na Scopus
    Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography-mass spectrometry
    (2015) PASSOS-CASTILHO, Ana Maria; CARVALHO, Valdemir Melechco; CARDOZO, Karina Helena Morais; KIKUCHI, Luciana; CHAGAS, Aline Lopes; GOMES-GOUVEA, Michele Soares; MALTA, Fernanda; NASTRI, Ana Catharina de Seixas-Santos; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; GRANATO, Celso Francisco Hernandes
    Background: Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers. Methods: An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases. Results: The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols. Conclusions: UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.
  • conferenceObject
    Serum Lipidomic Profiling for Screening Potential Biomarkers of Liver Cirrhosis among Patients with Chronic Hepatitis C
    (2015) PASSOS-CASTILHO, Ana Maria; FERRAZ, Maria Lucia; CARVALHO, Valdemir M.; CARDOZO, Karina H.; KIKUCHI, Luciana; CHAGAS, Aline; PINHO, Joao Renato R.; GOMES-GOUVEA, Michele S.; MALTA, Fernanda; CARRILHO, Flair J.; GRANATO, Celso
  • article 20 Citação(ões) na Scopus
    Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival
    (2014) KIKUCHI, Luciana; MENEZES, Marcos; CHAGAS, Aline L.; TANI, Claudia M.; ALENCAR, Regiane S. S. M.; DINIZ, Marcio A.; ALVES, Venancio A. F.; D'ALBUQUERQUE, Luiz Augusto Carneiro; CARRILHO, Flair Jose
    AIM: To evaluate outcomes of radiofrequency ablation (RFA) therapy for early hepatocellular carcinoma (HCC) and identify survival-and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography (CT) or magnetic resonance imaging (MRI) (single nodule of <= 5 cm, or multi-(up to 3) nodules of <= 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Cancer do Estado de Sao Paulo, Brazil were enrolled in the study. RFA of the liver tumors (with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response (absence of enhancing tissue at the tumor site) or incomplete response (enhancing tissue remaining at the tumor site). Overall survival and disease-free survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients (age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo (range, 1-33). The study population showed predominance of male sex (76%), less severe liver disease (Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor (65%). The maximum tumor diameters ranged from 10 to 50 mm (median, 26 mm). The initial (immediately post-procedure) rate of RFA-induced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule (vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema (resolved with intervention) and intestinal perforation (led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis (HR = 15; 95% CI: 3-76 mo; P = 0.001). The 1- and 2-year cumulative disease-free survival rates were 65% and 36%, respectively. CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.
  • article 38 Citação(ões) na Scopus
    The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib
    (2017) BRANCO, Fernanda; ALENCAR, Regiane S. M.; VOLT, Fernanda; SARTORI, Giovana; DODE, Andressa; KIKUCHI, Luciana; TANI, Claudia M.; CHAGAS, Aline L.; PFIFFER, Tulio; HOFF, Paulo; CARRILHO, Flair J.; MATTOS, Angelo Alves de
    Background and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response , which can be eavaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil, Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database Results. Cirrhosis was present in 94% of patients, 85.6% were child-pugh A, 80.3%BCLC-C,81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1. The median duration of treatment was 10.1 months (range: 0.1-47 months). The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%). The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.
  • conferenceObject
    Hepatitis B and C as Risk Factors for Early Hepatocellular Carcinoma Across South America
    (2016) CHAN, Aaron J.; BALDERRAMO, Domingo; KIKUCHI, Luciana; BALLERGA, Esteban Gonzalez; PRIETO, Jhon; TAPIAS, Monica; IDROVO, Victor; DAVALOS, Milagros; CAIRO, Fernando; BARREYRO, Fernando; PAREDES, Sebastian; HERNANDEZ, Nelia; AVENDANO, Karla; FERRER, Javier Diaz; YANG, Ju Dong; CARRERA, Enrique; RODRIGUEZ, Pablo; HIRSCH, Bruno; MATTOS, Angelo Z.; CARRILHO, Flair J.; ROBERTS, Lewis R.; DEBES, Jose
  • article 9 Citação(ões) na Scopus
    Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer
    (2016) MOREIRA, Joao Paulo; MALTA, Fernanda de Mello; DINIZ, Marcio Augusto; KIKUCHI, Luciana; CHAGAS, Aline Lopes; LIMA, Livia de Souza Botelho; GOMES-GOUVEA, Michele Soares; CASTRO, Vanessa Fusco Duarte de; SANTANA, Rubia Anita Ferraz; SUMITA, Nairo Massakazu; VEZOZZO, Denise Cerqueira Paranagua; CARRILHO, Flair Jose; PINHO, Joao Renato Rebello
    Background: Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. Method of study: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). Results: the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). Conclusions: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.
  • article 14 Citação(ões) na Scopus
    Hepatocellular Carcinoma Management in Nonalcoholic Fatty Liver Disease Patients Applicability of the BCLC Staging System
    (2016) KIKUCHI, Luciana; OLIVEIRA, Claudia P.; ALVARES-DA-SILVA, Mario R.; TANI, Claudia M.; DINIZ, Marcio A.; STEFANO, Jose T.; CHAGAS, Aline L.; ALENCAR, Regiane S. S. M.; VEZOZZO, Denise C. P.; SANTOS, Gilmar R.; CAMPOS, Priscila B.; ALVES, Venancio A. F.; RATZIU, Vlad; CARRILHO, Flair J.
    Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for,patients with HCC arising from NAFLD. Methods: Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated. Results: There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively. Conclusions: The BCLC system is applied in most cases of NAFLD-related HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients.
  • conferenceObject
    TUMOR RESPONSE EVALUATION ACCORDING TO MRECIST CRITERIA IN PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED WITH TACE-DRUG ELUTING BEADS
    (2012) CHAGAS, A. L.; KIKUCHI, L.; FREITAS, N. S.; SANTOS, A. C. B.; ALENCAR, R. S. S. M.; TANI, C. M.; MOREIRA, A. M.; ROCHA, M. S.; D'ALBUQUERQUE, L. A. C.; CARNEVALE, F. C.; CARRILHO, F. J.
    Introduction: Transarterial chemoembolization (TACE) is efficient in reduce tumoral growth and increase survival in patients with hepatocellular carcinoma (HCC). Drug eluting beads (DEB) is an embolizing device that slowly releases chemotherapy to decrease systemic toxicity during TACE. Initial studies showed that TACE-DEB is superior to conventional TACE regarding tumor response and toxicity. There is no study in our population that evaluate HCC response to TACE-DEB, according to mRECIST criteria. Objective: The aim of this study is to evaluate tumor response according to mRECIST criteria in patients with HCC treated with TACE-DEB. Methods: In the period of the study, 53 patients with HCC were treated with 65 sessions of TACE-DEB loadeD with doxorubicin 50mg. Tumor response was evaluated one month after the procedure with CT or MRI according to mRECIST criteria. Results: Median age was 62 years and 74% were male. The majority of the patients were cirrhotic (89% – CHILD A 65% and CHILD B 35%). Etilogy of liver disease was HCV in 27/53 (51%), HBV in 8/53 (15%), alcohol in 10/53 (19%) and NASH in 3/53 (6%). According to BCLC staging system, 51% was BCLC A and 49% was BCLC B. Most patients had one nodule (66%). No patient presented with extrahepatic metastasis or macroscopic vascular invasion. Tumor response according to mRECIST was possible after 60 procedures. Complete response was reached in 12/60 (20%), partial response in 31/60 (52%), stable disease in 4/60 (6.5%) and progressive disease in 13/60 (21.5%). Conclusion: In patients with compensated liver cirrhosis and HCC, TACE-DEB was efficient in induce tumor response according to mRECIST criteria, and in our study objective response (complete response + partial response) was reached in 72% os cases. Further studies are necessary to evaluate survival and predictors factors of response.