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1.
Clin Transl Gastroenterol ; 11(9): e00239, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33094960

RESUMO

INTRODUCTION: Liver cirrhosis and its complication - hepatocellular carcinoma (HCC) - have been associated with increased exhaled limonene. It is currently unclear whether this increase is more strongly associated with the presence of HCC or with the severity of liver dysfunction. METHODS: We compared the exhaled breath of 40 controls, 32 cirrhotic patients, and 12 cirrhotic patients with HCC using the Breath Biopsy platform. Breath samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. Limonene levels were compared between the groups and correlated to bilirubin, albumin, prothrombin time international normalized ratio, and alanine aminotransferase. RESULTS: Breath limonene concentration was significantly elevated in subjects with cirrhosis-induced HCC (M: 82.1 ng/L, interquartile range [IQR]: 16.33-199.32 ng/L) and cirrhosis (M: 32.6 ng/L, IQR: 6.55-123.07 ng/L) compared with controls (M: 6.2 ng/L, IQR: 2.62-9.57 ng/L) (P value = 0.0005 and 0.0001, respectively) with no significant difference between 2 diseased groups (P value = 0.37). Levels of exhaled limonene correlated with serum bilirubin (R = 0.25, P value = 0.0016, r = 0.51), albumin (R = 0.58, P value = 5.3e-8, r = -0.76), and international normalized ratio (R = 0.29, P value = 0.0003, r = 0.51), but not with alanine aminotransferase (R = 0.01, P value = 0.36, r = 0.19). DISCUSSION: Exhaled limonene levels are primarily affected by the presence of cirrhosis through reduced liver functional capacity, as indicated by limonene correlation with blood metrics of impaired hepatic clearance and protein synthesis capacity, without further alterations observed in subjects with HCC. This suggests that exhaled limonene is a potential non-invasive marker of liver metabolic capacity (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A388).


Assuntos
Carcinoma Hepatocelular/diagnóstico , Limoneno/análise , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Compostos Orgânicos Voláteis/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Testes Respiratórios , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
2.
BMC Cancer ; 20(1): 504, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487089

RESUMO

BACKGROUND: The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. METHODS: A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). RESULTS: Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system ("ASAR"). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570-0.871) in the derivation, 0.700 (95% CI = 0.445-0.905) in the internal validation, and 0.680 (95% CI = 0.652-0.707) in the external validation, respectively. Patients with ASAR< 4 showed significantly longer OS than patients with ASAR≥4 in all three datasets (all P < 0.001). Among Child-Pugh class B patients, a modified model without TACE response, i.e., "ASA(R)", discriminated OS with a c-index of 0.788 (95% CI, 0.703-0.876) in the derivation, and 0.745 (95% CI, 0.646-0.862) in the internal validation, and 0.670 (95% CI, 0.605-0.725) in the external validation, respectively. Child-Pugh B patients with ASA(R) < 4 showed significantly longer OS than patients with ASA(R) ≥ 4 in all three datasets (all P < 0.001). CONCLUSIONS: ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/terapia , Idoso , Bilirrubina/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Tomada de Decisão Clínica/métodos , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Critérios de Avaliação de Resposta em Tumores Sólidos , Medição de Risco/métodos , Fatores de Risco , Albumina Sérica/análise , Índice de Gravidade de Doença , Análise de Sobrevida
3.
Int J Mol Sci ; 20(3)2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30704150

RESUMO

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan⁻Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 µU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.


Assuntos
Carcinoma Hepatocelular/fisiopatologia , Resistência à Insulina/fisiologia , Neoplasias Hepáticas/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/metabolismo , Jejum/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade
4.
Pract Radiat Oncol ; 7(3): 173-182, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28343896

RESUMO

PURPOSE: This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. RESULTS: A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/ß of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). CONCLUSIONS: ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival.


Assuntos
Bilirrubina/sangue , Neoplasias Hepáticas/radioterapia , Fígado/fisiologia , Radiocirurgia/efeitos adversos , Albumina Sérica Humana/análise , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/fisiopatologia , Neoplasias dos Ductos Biliares/radioterapia , Biomarcadores , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/radioterapia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/fisiopatologia , Colangiocarcinoma/radioterapia , Relação Dose-Resposta à Radiação , Feminino , Humanos , Fígado/efeitos da radiação , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia , Radiocirurgia/métodos , Dosagem Radioterapêutica
5.
J Comput Assist Tomogr ; 40(5): 692-700, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27560010

RESUMO

PURPOSE: The aim of this study was to investigate the role of dynamic contrast-enhanced magnetic resonance imaging (MRI) in evaluation of blood flow changes related to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) procedures in patients with hepatocellular carcinoma (HCC) lesions. METHODS: Fifty-four patients, with biopsy-proven HCC, who underwent TACE or RFA, were evaluated, 1 month after treatment, with upper abdominal MRI examination. Multiplanar T2-weighted, T1-weighted, and dynamic contrast-enhanced sequences were acquired. Dedicated perfusion software (T1 Perfusion Package, Viewforum; Philips Medical Systems, The Netherlands) was used to generate color permeability maps. After placing regions of interest in normal hepatic parenchyma, in successfully treated lesions, and in area of recurrence, the following perfusion parameters were calculated and statistically analyzed: relative arterial, venous, and late enhancement; maximum enhancement; maximum relative enhancement, and time to peak. RESULTS: Twenty-one of 54 patients had residual disease, and perfusion parameters values measured within tumor tissue were: relative arterial enhancement median, 42%; relative venous enhancement median, 69%; relative late enhancement median, 57.7%; maximum enhancement median, 749.6%; maximum relative enhancement median, 69%; time to peak median, 81.1 seconds. As for all the evaluated parameters, a significant difference (P < 0.05) was found between residual viable tumor tissue and effective treated lesions. CONCLUSIONS: Dynamic contrast-enhanced MRI represents a complementary noninvasive tool that may offer quantitative and qualitative information about HCC lesions treated with TACE and RFA.


Assuntos
Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/terapia , Circulação Hepática , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/terapia , Angiografia por Ressonância Magnética/métodos , Idoso , Velocidade do Fluxo Sanguíneo , Carcinoma Hepatocelular/diagnóstico por imagem , Ablação por Cateter/métodos , Quimioembolização Terapêutica/métodos , Meios de Contraste , Feminino , Gadolínio DTPA , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
6.
J Med Assoc Thai ; 99(5): 572-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27501613

RESUMO

OBJECTIVE: To find the incidence of moderate to severe pain after percutaneous radiofrequency ablation (RFA) in patients with hepatocellular carcinoma and to identify the factors affecting unwanted pain scores. MATERIAL AND METHOD: This prospective study was conducted on patients who underwent percutaneous radiofrequency ablation under intravenous sedation and local anesthesia. The pain scores were obtained from 18 to 24 hours after the procedure. Moderate to severe pain was defined as a value of 4 or more on the Numeric Rating Scale (NRS). Data on patients' factors, tumor characteristics, procedural factors, anesthetic management, postoperative treatment and perioperative complication was collected RESULTS: A total of 190 patients were enrolled, comprised of 134 men (70.5%) and 56 women (29.5%). The mean age of the patients was 63.3 ± 11.1 years. The incidence of moderate to severe pain on movement (an NRS value equal to or greater than 4) was 11.6% (22 out of 190 patients). A univariate analysis revealed that two factors--patients with multiple tumors (more than two tumors), and an ablation time of greater than 30 minutes--seemed to be related to an NRS equal to or greater than 4. Nevertheless, after entering those two factors into a multiple regression model, neither factor was associated with the moderate to severe pain scores. CONCLUSION: The incidence of undesired pain scores after percutaneous radiofrequency ablation in our institution was around 10%, and the rate of complication was very low.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Dor/fisiopatologia , Adulto , Idoso , Carcinoma Hepatocelular/fisiopatologia , Ablação por Cateter/métodos , Feminino , Humanos , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Complicações Pós-Operatórias , Estudos Prospectivos , Índice de Gravidade de Doença
7.
PLoS One ; 11(7): e0159530, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27434062

RESUMO

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) have underlying liver disease, therefore, precise preoperative evaluation of the patient's liver function is essential for surgical decision making. METHODS: We developed a grading system incorporating only two variables, namely, the serum albumin level and the indocyanine green retention rate at 15 minutes (ICG R15), to assess the preoperative liver function, based on the overall survival of 1868 patients with HCC who underwent liver resection. We then tested the model in a European cohort (n = 70) and analyzed the predictive power for the postoperative short-term outcome. RESULTS: The Albumin-Indocyanine Green Evaluation (ALICE) grading system was developed in a randomly assigned training cohort: linear predictor = 0.663 × log10ICG R15 (%)-0.0718 × albumin (g/L) (cut-off value: -2.20 and -1.39). This new grading system showed a predictive power for the overall survival similar to the Child-Pugh grading system in the validation cohort. Determination of the ALICE grade in Child-Pugh A patients allowed further stratification of the postoperative prognosis. This result was reproducible in the European cohort. Determination of the ALICE grade allowed better prediction of the risk of postoperative liver failure and mortality (ascites: grade 1, 2.1%; grade 2, 6.5%; grade 3, 16.0%; mortality: grade 1, 0%; grade 2, 1.3%; grade 3, 5.3%) than the previously reported model based on the presence/absence of portal hypertension. CONCLUSIONS: This new grading system is a simple method for prediction of the postoperative long-term and short-term outcomes.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatectomia , Verde de Indocianina/farmacocinética , Neoplasias Hepáticas/diagnóstico , Albumina Sérica/metabolismo , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Fígado/metabolismo , Fígado/fisiopatologia , Fígado/cirurgia , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Período Pré-Operatório , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Falha de Tratamento
8.
J Gastroenterol Hepatol ; 31(7): 1336-41, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26860846

RESUMO

BACKGROUND AND AIM: The Cancer of the Liver Italian Program (CLIP) score is a commonly used staging system for hepatocellular carcinoma (HCC) helpful with predicting prognosis of advanced HCC. CLIP uses the Child-Turcotte-Pugh (CTP) score to evaluate liver reserve. A new scoring system, the albumin-bilirubin (ALBI) grade, has been proposed as they objectively evaluate liver reserve. We examined whether the modification of CLIP with ALBI retained its prognosis prediction for patients with advanced HCC. METHODS: We included patients who received first-line antiangiogenic therapy for advanced HCC. Liver reserve was assessed using CTP and ALBI scores, which were then incorporated into CLIP and ALBI-CLIP, respectively. To assess their efficacies of prognostic prediction, the Cox's proportional hazard model and concordance indexes were used. RESULTS: A total of 142 patients were included; 137 of them were classified CTP A and 5 patients CTP B. Patients could be divided into four or five groups with different prognosis according to CLIP and ALBI-CLIP, respectively. Higher R(2) (0.249 vs 0.216) and lower Akaike information criterion (995.0 vs 1001.1) were observed for ALBI-CLIP than for CLIP in the Cox's model predicting overall survival. ALBI-CLIP remained an independent predictor for overall survival when CLIP and ALBI-CLIP were simultaneously incorporated in Cox's models allowing variable selection with adjustment for hepatitis etiology, treatment, and performance status. The concordance index was also higher for ALBI-CLIP than for CLIP (0.724 vs 0.703). CONCLUSIONS: Modification of CLIP scoring with ALBI, which objectively assesses liver reserve, retains and might have improved prognosis prediction for advanced HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Fígado/fisiologia , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Biomarcadores Tumorais/sangue , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Prognóstico , Albumina Sérica , Adulto Jovem
9.
Ultrasound Med Biol ; 42(2): 438-46, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26626491

RESUMO

Diffuse hepatocellular carcinoma (HCC) is a complex affliction in which comorbidities can bias global outcome of cancer therapy. Better methods are thus warranted to directly assess effects of therapy on tumor angiogenesis and growth. As tumor angiogenesis is invariably associated with changes in local blood flow, we assessed the utility of ultrasound imaging in evaluation of the efficacy of anti-angiogenic therapy in a spontaneous transgenic mouse model of HCC. Blood flow velocities were measured monthly in the celiac trunk before and after administration of sorafenib or bevacizumab at doses corresponding to those currently used in clinical practice. Concordant with clinical experience, sorafenib, but not bevacizumab, reduced microvascular density and suppressed tumor growth relative to controls. Evolution of blood flow velocities correlated with microvascular density and with the evolution of tumor size. Ultrasound imaging thus provides a useful non-invasive tool for preclinical evaluation of new anti-angiogenic therapies for HCC.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Ultrassonografia/métodos , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Circulação Hepática/efeitos dos fármacos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/fisiopatologia , Masculino , Camundongos , Camundongos Transgênicos , Neovascularização Patológica/complicações , Neovascularização Patológica/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
10.
J Hepatol ; 64(1): 79-86, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26325538

RESUMO

BACKGROUNDS & AIMS: To assess the relationship existing between hepatic venous pressure gradient (HVPG) and the occurrence of post-hepatectomy liver failure (PHLF) grade B/C after resection of hepatocellular carcinoma (HCC) and persistent worsening of liver function. METHODS: Data from 70 consecutive prospectively enrolled HCC patients undergoing resection were collected and analysed. PHLF grade B/C was defined by the International Study Group of Liver Surgery recommendations. The appearance of unresolved decompensation was also analysed. RESULTS: Postoperative and 90-day mortality were null. The median HVPG value was 9mmHg (range: 4-18) and the median Model for End-stage Liver Disease (MELD) score was 8 (range: 6-14); 34 patients had an HVPG ⩾10mmHg (48.6%). Forty-nine patients had an uneventful (Grade A) postoperative course, including 17 with an HVPG ⩾10mmHg (24.2% of 70 patients). Grade B complications occurred in 20 patients (3 with an HVPG <10mmHg and 17 with an HVPG ⩾10mmHg; p<0.001); only one grade C complication occurred in a patient with an HVPG <10mmHg, subsequently successfully undergoing liver transplantation. Median MELD score returned to preoperative values after a transient postoperative increase, regardless of the HVPG values; after three months, it returned to the preoperative of 8 in patients with an HVPG <10mmHg and of 9 in patients with an HVPG ⩾10mmHg (p=0.077 and 0.076 at paired test, respectively). CONCLUSIONS: The hepatic venous pressure gradient can be used before surgery to stratify the risk of PHLF but the proposed cut-off of 10mmHg excludes approximately one-quarter of the patients who would benefit from surgery without short to mid-term postoperative sequelae.


Assuntos
Carcinoma Hepatocelular/cirurgia , Veias Hepáticas/fisiopatologia , Neoplasias Hepáticas/cirurgia , Cuidados Pré-Operatórios , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/fisiopatologia , Feminino , Humanos , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Pressão Venosa/fisiologia
11.
Nat Prod Commun ; 10(8): 1403-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26434128

RESUMO

The aim of this work was to evaluate in vitro the genotoxic and/or antigenotoxic effects of resveratrol (RESV) and pterostilbene (PTER) on HepG2 cells. Moreover, additional tests were performed to evaluate early and late apoptosis events induced by the tested stilbenes. RESV and PTER did not show any genotoxic activity. As regards antigenotoxicity testing, RESV and PTER showed a typical, U-shaped hormetic dose-response relationship characterized by a biphasic trend with small quantities having opposite effects to large ones. HepG2 cells treated with PTER exhibited a marked increase in early apoptosis (40.1%) at 250 microM; whereas, the highest concentration tested for both RESV and PTER significantly increased the proportion of HepG2 cells undergoing late apoptosis (32.5 and 51.2%, respectively). The observed pro-apoptotic activity could, at least in part, explain the hormetic response observed when the compounds were tested for antigenotoxicity (i.e., in the presence of induced DNA damage).


Assuntos
Carcinoma Hepatocelular/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Dano ao DNA/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/química , Resveratrol , Estilbenos/efeitos adversos , Estilbenos/química
12.
Ultrasound Med Biol ; 41(12): 3079-87, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26371403

RESUMO

This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 ± 4.9 mm, 86 patients), 47 well-differentiated HCCs (wHCCs) and 47 moderately-differentiated HCCs (mHCCs): I(e) (early phase) = I(te) (tumor) - I(le) (liver), I(p) (post-vascular phase) = I(tp) (tumor) - I(lp) (liver), I(ep) = I(e) - I(p). The area under the receiver operating characteristic curve with the best cutoff value (I(e), 13.2, I(p), -4.5, I(ep), 21.3) for discriminating between wHCC and mHCC was 0.6922 for Ie, 0.7680 for Ip and 0.7925 for Iep, which indicated a significantly greater ability to differentiate between wHCC and mHCC compared with visual/qualitative assessment (early phase, 0.6170, p = 0.04; post-vascular phase, 0.6702, p = 0.01; both phases, 0.7021, p = 0.04). In conclusion, I(ep) was found to have the highest diagnostic ability, suggesting it is a promising parameter for the cellular differentiation of HCCs with CEUS.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Diferenciação Celular/fisiologia , Neoplasias Hepáticas/diagnóstico por imagem , Microbolhas , Idoso , Carcinoma Hepatocelular/fisiopatologia , Meios de Contraste , Feminino , Fluorocarbonos , Humanos , Aumento da Imagem , Fígado/diagnóstico por imagem , Fígado/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Ultrassonografia
13.
J Cancer Res Clin Oncol ; 141(7): 1311-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25648362

RESUMO

PURPOSE: We evaluated the prognosis of hepatocellular carcinoma (HCC) patients with Child-Pugh (C-P) class A based on FIB-4 index, which is a liver fibrosis marker. PATIENTS AND METHODS: A total of 915 HCC patients with C-P class A were investigated. We assessed the prognosis using FIB-4 index, and factors associated with survival rates were analyzed in these patients. RESULTS: When patients were categorized according to FIB-4 index as <2.0 (n = 93), ≥ 2.0 and <4.0 (n = 311), and ≥ 4.0 (n = 511), survival rates at 5 years were 70.5% [95% confidence interval (CI) 59.0-79.9], 56.4% (95% CI 50.1-62.5), and 47.1% (95% CI 42.2-52.1), respectively. Patients with FIB-4 index <2.0 had a higher survival rate than the other groups (≥ 4.0 vs ≥ 2.0 and <4.0, p = 0.010; ≥ 2.0 and <4.0 vs <2.0, p = 0.028). We were able to predict prognosis in patients with C-P score 5 by FIB-4 index, but survival rate did not significantly differ in patients with C-P score 6. Multivariate analysis identified C-P score, FIB-4 index [≥ 2.0 and <4.0; hazard ratios (HRs) 1.638 (95% CI 1.084-2.474); p = 0.019/≥ 4.0; HR 1.828 (95% CI 1.217-2.744); p = 0.004], Lens culinaris agglutinin-reactive α-fetoprotein, tumor size, number, vascular invasion, antiviral therapy, and hepatectomy as independent predictive factors for survival. CONCLUSIONS: The FIB-4 index is useful for assessing prognosis in HCC patients with C-P class A, especially those with C-P score 5.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Indicadores Básicos de Saúde , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Fígado/fisiopatologia , Fatores Etários , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Biomarcadores/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/complicações , Testes de Função Hepática/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico
14.
J Clin Oncol ; 33(6): 550-8, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25512453

RESUMO

PURPOSE: Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade. PATIENTS AND METHODS: We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n = 5,097) and other clinical situations (patients undergoing resection [n = 525] or sorafenib treatment for advanced HCC [n = 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n = 501). RESULTS: The model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function. CONCLUSION: The ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/fisiopatologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/fisiopatologia , Fígado/fisiopatologia , Albumina Sérica/metabolismo , Idoso , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Gradação de Tumores , Estadiamento de Neoplasias
15.
J Hepatol ; 60(5): 969-74, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24362073

RESUMO

BACKGROUND & AIMS: Liver resection is generally restricted to patients without clinically significant portal hypertension (Hepatic Venous Pressure Gradient - HVPG - ⩽10mmHg) and several teams perform transjugular HVPG measurements as part of the pre-operative work-up. The present study investigates whether a non-invasive Computed Tomography (CT)-based assessment could be as accurate as the invasive transjugular measurement. METHODS: A cohort of patients with hepatocellular carcinoma (HCC) treated by resection (n=36) or transplantation (n=39) was selected (mean age: 61±9.2years, male/female ratio: 4/1). Pre-operative CTs were read by two independent investigators, and potential CT-based HVPG predictors were compared to the transjugular HVPG measurements. A validation was conducted on another cohort of 70 non-surgical patients. RESULTS: The invasive HVPG values were significantly correlated to liver/spleen volume ratio, spleen volume, platelet count, and peri-hepatic ascites (p<0.001), which all showed high inter-observer agreements (intra-class correlation coefficients ⩾0.927, Kappa ⩾0.945). The presence of a HVPG >10mmHg was best predicted by the liver/spleen volume ratio (AUC: 0.883 [0.805-0.960]) and the peri-hepatic ascites (p<0.001). These two variables were combined into an accurate model for predicting HVPG >10mmHg (AUC: 0.911 [0.847-0.975]), with sensitivity, specificity, and positive and negative predictive values of 92%, 79%, 91%, and 81%. The model was also accurate in the validation cohort with an AUC of 0.820 [0.719-0.921]. The computed formula was: CONCLUSIONS: The proposed CT-based model showed a high accuracy in the prediction of HVPG and, if further confirmed by prospective validation, could replace the invasive transjugular assessment in patients not requiring a biopsy of the non-tumoral liver.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/fisiopatologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/fisiopatologia , Pressão na Veia Porta , Tomografia Computadorizada por Raios X/métodos , Idoso , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Feminino , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/diagnóstico por imagem , Veias Jugulares/diagnóstico por imagem , Veias Jugulares/fisiopatologia , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Baço/diagnóstico por imagem
16.
J Palliat Med ; 16(7): 780-5, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23790184

RESUMO

BACKGROUND: Hospice care is important for patients with terminal hepatocellular carcinoma (HCC), especially in endemic areas of viral hepatitis. Differences between hospice care and usual care for geriatric HCC inpatients have not yet been explored in a nationwide survey. OBJECTIVE: The study's purpose was to analyze differences between hospice care and usual care for geriatric HCC inpatients in a nationwide survey. METHODS: This nationwide, population-based study used data obtained from the Taiwan National Health Insurance Database. Patients with terminal HCC who were ≥65 years old and received their end-of-life care in the hospital between January 2001 and December 2004 were recruited. The comparison group was selected by propensity score matching from patients receiving usual care in acute wards. RESULTS: We enrolled 729 terminal HCC patients receiving inpatient hospice care and 729 matched controls selected from 2482 HCC patients receiving usual care. Hospice care patients were treated mainly by family medicine doctors (36%) and oncologists (26%), while usual care patients were treated mainly by gastroenterologists (60.2%). The natural opium alkaloids were used more in the hospice care group than in the usual care group (72.7% versus 25.5%, P<0.001), whereas the length of stay (8±7.7 days versus 14.1±14.3 days, P<0.001), aggressive procedures (all P<0.005), and medical expenses (all P<0.001) were significantly less in the hospice care group. CONCLUSION: HCC patients in hospice wards received more narcotic palliative care, underwent fewer aggressive procedures, and incurred lower costs than those in acute wards. Hospice care should be promoted as a viable option for terminally ill, elderly HCC patients.


Assuntos
Analgésicos Opioides/uso terapêutico , Carcinoma Hepatocelular/economia , Cuidados Paliativos na Terminalidade da Vida/economia , Cuidados para Prolongar a Vida/economia , Neoplasias Hepáticas/economia , Cuidados Paliativos/economia , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/normas , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/terapia , Custos e Análise de Custo , Feminino , Pesquisas sobre Atenção à Saúde , Cuidados Paliativos na Terminalidade da Vida/métodos , Cuidados Paliativos na Terminalidade da Vida/normas , Mortalidade Hospitalar , Humanos , Pacientes Internados/estatística & dados numéricos , Revisão da Utilização de Seguros/estatística & dados numéricos , Cuidados para Prolongar a Vida/normas , Cuidados para Prolongar a Vida/estatística & dados numéricos , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/terapia , Masculino , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Pontuação de Propensão , Padrão de Cuidado , Taiwan/epidemiologia , Doente Terminal/estatística & dados numéricos
18.
Support Care Cancer ; 21(10): 2655-62, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23653014

RESUMO

OBJECTIVES: The aims of this cross-sectional study were to explore the agreement in symptom evaluation results between patients and their family caregivers and to search for the possible factors influencing the agreement. METHODS: A convenience sample of 280 dyads consisting of hepatocellular carcinoma patients and their family caregivers was included in this study. All of them completed the symptom checklist of Chinese version of the M. D. Anderson symptom inventory and the evaluations of six common symptoms of hepatocellular carcinoma. RESULTS: The levels of agreement ranged from moderate to substantial. A number of factors associated with caregivers (particularly depression state, age, others helping to care for the patient or not, and the relationship with patient) and patients (traditional Chinese medicine treatment, religion, KPS scores, and educational levels) were significantly correlated with levels of disparity on some symptoms. CONCLUSION: The study illustrates that family caregivers of hepatocellular carcinoma patients can provide reasonable reports on patients' symptoms. Healthcare providers need to pay special and sufficient attention to the caregivers' depression.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/psicologia , Cuidadores/psicologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/psicologia , Carcinoma Hepatocelular/fisiopatologia , China , Estudos Transversais , Depressão/diagnóstico , Depressão/etiologia , Família/psicologia , Feminino , Humanos , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Autorrelato , Avaliação de Sintomas
20.
Acad Radiol ; 20(8): 1037-40, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23537719

RESUMO

RATIONALE AND OBJECTIVES: The end point of chemoembolization for hepatocellular carcinoma is qualitative. We intended to determine the feasibility of measuring intra-arterial pressure changes after chemoembolization and hypothesized that pressures would increase in the distal hepatic artery after the procedure. MATERIALS AND METHODS: Before and after chemoembolization, systemic (S) systolic and mean pressures were measured along with celiac (C), lobar (L), and distal (D) hepatic artery pressures with a pressure wire. Corrected pressures were defined as a ratio with S as the denominator to account for intraprocedural S changes. Changes in the systolic and mean corrected pressures at each location (C/S, L/S, and D/S) were evaluated using paired t tests. Pressure changes in patients with and without tumor response using the Modified Response Evaluation Criteria in Solid Tumors were also compared. RESULTS: Sixteen tumors were treated in 15 patients. One patient had bilobar tumors with separate supplying arteries. The only significant pressure change was systolic D/S (P = .02), while mean D/S approached significance (P = .08). C/S and L/S did not change significantly after chemoembolization. Eleven of 16 patients had a complete response, whereas the other five had a partial response after chemoembolization. When comparing complete to partial responders, no changes in systolic or mean C/S, L/S, or D/S reached statistical significance (all P > .05). CONCLUSIONS: Measuring change in hepatic artery pressures is feasible. Distal intra-arterial corrected pressures increase significantly after chemoembolization. Further study to determine the ability to predict tumor necrosis at follow-up imaging is warranted.


Assuntos
Determinação da Pressão Arterial/instrumentação , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Pressão Sanguínea , Feminino , Artéria Hepática/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transdutores de Pressão , Resultado do Tratamento
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