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1.
Oncology ; 99(8): 491-498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34000725

RESUMO

INTRODUCTION: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. METHODS: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. RESULTS: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. CONCLUSION: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
2.
Oncology ; 99(8): 507-517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33946070

RESUMO

INTRODUCTION: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). METHODS: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. RESULTS: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. CONCLUSION: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Pontuação de Propensão , Quinolinas/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
3.
Oncology ; 99(5): 327-335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33677453

RESUMO

INTRODUCTION: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. METHODS: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. RESULTS: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. CONCLUSION: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Quinolinas/administração & dosagem , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Taxa de Sobrevida
4.
Front Sports Act Living ; 3: 628153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33644754

RESUMO

Most social impact research considers the pre- and post-event social impacts of sporting events to investigate the effects of these events on residents' or consumers' intention or attitude. This study focused on the qualitative differences between pre-event expected social impacts (T1) and post-event experienced social impacts (T2). Then, it investigated viewing behaviors due to the expected social impacts, and intentions to support events from experienced social impacts. The Rugby World Cup 2019 in Japan provided the context for the study. Panel data were collected from the same Tokyo residents in T1 (3 months before the event) and T2 (4 months after the event). The Internet-based survey consisted of six social impact constructs, framed as expectations in T1 and experiences in T2. Both dependent variables, viewing behavior and supporting events, were measured in T2, after the event occurred. Two expected impacts had a significant positive association with viewing behavior, while three experienced social impacts had a significant positive association with event support intention. The main contribution of this article is extending the understanding of the role of social impact as a predictor variable for residents' behavior and intention to support events by using panel data, which enabled the authors to obtain more robust results. The current study extends the knowledge on consumer expectancy role and social exchange theory in the context of the social impacts of sporting events.

5.
Intern Med ; 60(6): 829-837, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33087674

RESUMO

Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag. Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed. Results The median platelet count increased significantly from 4.5×104/µL before lusutrombopag treatment to 7.2×104/µL before the invasive procedure (p<0.01), and patients undergoing 49 of the 53 (92%) treatment regimens succeeded in undergoing invasive procedures without needing platelet transfusions. In patients who received lusutrombopag treatment repeatedly, the median platelet count significantly increased following the second administration of lusutrombopag, and the effects of lusutrombopag were similar between the first and second administration. A multivariate analysis identified the absence of diabetes mellitus (odds ratio, 5.56 for presence; p=0.04) as a significant and independent predictor of a response to lusutrombopag. Conclusion Lusutrombopag treatment significantly increased platelet counts in patients with chronic liver disease, making it possible to receive invasive procedures. The treatment produced identical effects when it was repeated. The efficacy of lusutrombopag might be decreased in patients with diabetes mellitus.


Assuntos
Hepatopatias , Trombocitopenia , Doença Crônica , Cinamatos , Humanos , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Receptores de Trombopoetina , Estudos Retrospectivos , Tiazóis , Trombocitopenia/tratamento farmacológico
6.
Esophagus ; 18(3): 669-675, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33221955

RESUMO

BACKGROUND: The study aimed to investigate the efficacy of vonoprazan 10 mg compared with 20 mg in patients with erosive esophagitis. METHOD: Seventy-three patients with erosive esophagitis were randomly divided into two groups either vonoprazan 20 mg (n = 37) or 10 mg (n = 36). They were administered each dose for 4 weeks as the initial treatment followed by maintenance treatment with 10 mg for 8 weeks. The primary endpoints were mucosal healing rate and symptom relief at 4 weeks. The secondary endpoint was symptom relief at 12 weeks after the maintenance treatment. Mucosal healing was assessed endoscopically, and symptom relief was assessed using the FSSG score. RESULTS: At 4 weeks, the endoscopic healing rates of the 20 mg and 10 mg groups were 94.6% and 94.4%, respectively. The FSSG scores of the 20 mg and 10 mg groups were significantly decreased in both treatment groups from 13 (4-39) to 4 (0-25) and 14 (4-40) to 3 (0-29), respectively. At 12 weeks, the scores further decreased to 2 (0-13) and 2 (0-26), respectively. The vonoprazan 10 mg group showed a similar therapeutic effect to the 20 mg group in mucosal healing at 4 weeks and in symptom relief throughout the study period. When stratified by esophagitis grading, these findings were still demonstrated in grade A/B patients but not in grade C/D patients. CONCLUSION: Our findings suggest that initial treatment with vonoprazan 10 mg might be useful especially in patients with mild erosive esophagitis. Large controlled studies are warranted to confirm our investigation.

7.
Oncology ; 98(11): 787-797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32882687

RESUMO

BACKGROUND: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. METHODS: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. RESULTS: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors. CONCLUSION: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Taxa de Sobrevida
8.
Clin J Gastroenterol ; 13(6): 1233-1238, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32656649

RESUMO

The hepatitis C virus (HCV) NS5A-P32 deletion (P32del) confers potent resistance to NS5A inhibitors. Chronic hepatitis C patients in whom NS5A-P32del variants had emerged during prior direct-acting antiviral (DAA) therapy with an NS5A inhibitor show poor response to DAA retreatment. Here, we report three patients with HCV NS5A-P32del infection who were treated with sofosbuvir, velpatasvir plus ribavirin (SOF/VEL + RBV) in a real-world setting. The patients developed HCV NS5A-P32del, L31F + P32del, or L31V + P32del variants following failure of daclatasvir plus asunaprevir (DCV/ASV) therapy. One of the patients failed to respond to subsequent DCV/ASV and beclabuvir therapy, and the remaining two patients failed to respond to subsequent glecaprevir and pibrentasvir therapy. All three patients completed 24-week SOF/VEL + RBV therapy. Serum HCV RNA became negative at the end of the therapy in all three patients. Two patients with NS5A-P32del and NS5A-L31F + P32del achieved sustained virological response 12 weeks after completion of treatment (SVR12), but HCV relapsed in the remaining NS5A-L13V + P32del patient. Direct sequence analysis detected no additional variants within either the NS5A or NS5B regions at the time of relapse. In conclusion, three patients with prior NS5A-P32del-associated DAA treatment failure received 24 weeks of SOF/VEL + RBV therapy, and two of the patients achieved SVR12.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Carbamatos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento
9.
Mol Clin Oncol ; 12(1): 60-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814977

RESUMO

Although sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), the predictive factors sorafenib tolerance in intermediate-stage HCC cannot be accurately determined. The aim of the current study was to identify the predictive characteristics for the continuation of sorafenib treatment (≥400 mg) in patients with transarterial chemoembolization (TACE)-refractory intermediate HCC and to identify candidates for second-line sorafenib treatment. A total of 33 TACE-refractory intermediate patients with HCC that were treated with sorafenib, and who had reached progressive disease (PD), were analyzed in the present retrospective study. Of 33 patients, 6 patients (18.1%) were able to continue sorafenib treatment (≥400 mg) until PD, however, a total of 27 patients (71.9%) were unable to continue treatment (<400 mg). The current study compared the baseline characteristics parameters to sorafenib ≥400 mg and <400 mg using a logistic regression model. The overall survival (OS) of patients receiving sorafenib ≥400 mg treatment was significantly increased compared with patients receiving sorafenib treatment <400 mg [554.5 days (228-674) vs. 219 days (134-369); P=0.0315). A univariate analysis was performed and indicated that Age (<75 years; P=0.021), total cholesterol (>180 mg/dl; P=0.026) and cholinesterase (ChE; ≥220 U/l; P=0.024) were significant factors, and a multivariate analysis indicated that ChE (≥220 U/l) was a significant prognostic factor (HR: 11.9; 95% CI: 1.19-118.0; P=0.004). Both progression-free survival [279 (204-403) vs. 117.5 (63-197) days; P=0.0136] and OS [470 (277-679) vs. 171.5 (80-236) days; P=0.0004] were significantly increased in patients with ChE levels ≥220 U/l compared with patients exhibiting ChE levels <220 U/l. Baseline high value of ChE in intermediate-stage HCC predicts the ability to continue sorafenib treatment at ≥400 mg.

11.
Nihon Shokakibyo Gakkai Zasshi ; 116(12): 1030-1038, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31827043

RESUMO

A 77-year-old Japanese man with a gastrointestinal stromal tumor (GIST) had undergone a duodenectomy 11 years prior. At that time, he had an incidentally detected left renal cell carcinoma, for which he underwent a nephrectomy and was followed-up at our institution. Twenty-four months after the nephrectomy, a 13-mm low-density mass was found on abdominal computed tomography (CT). Contrast-enhanced ultrasonography indicated an irregular hyperenhancement in the vascular phase and a defect on the post-vascular image. A tumor biopsy for differential diagnosis revealed that the tumor was a GIST. Since positron emission tomography-CT and capsule endoscopy revealed no evidence of a primary lesion, we performed a partial hepatectomy without adjuvant treatment. Microscopic examination revealed that the tumor consisted of uniform spindle cells with a fascicular growth pattern. Immunohistochemical examination revealed c-kit and CD34 expressions, similar to those found in the resected duodenal GIST specimen 11 years prior. We diagnosed metastatic liver tumor from the duodenal GIST resected 11 years prior. The patient remains alive without disease recurrence 24 months after the hepatectomy. Long-term surveillance is required after resection of a high-risk primary GIST.


Assuntos
Duodeno , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Idoso , Hepatectomia , Humanos , Masculino , Recidiva Local de Neoplasia
12.
J Gastroenterol ; 52(3): 366-375, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27422771

RESUMO

BACKGROUND: Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases. METHODS: Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed. RESULTS: Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325). CONCLUSIONS: HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/sangue , Hepatite B Crônica/cirurgia , Transplante de Fígado , Adulto , Idoso , Antivirais/uso terapêutico , Biomarcadores/sangue , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Seguimentos , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Humanos , Imunoglobulinas/uso terapêutico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Recidiva , Adulto Jovem
13.
Hepatol Res ; 47(10): 1053-1060, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27862729

RESUMO

AIMS: We retrospectively analyzed the clinical outcome and prognostic parameters in patients with hepatocellular carcinoma (HCC) and bone metastases who had received treatment with zoledronic acid (ZOL). METHODS: Ninety-nine HCC patients with bone metastases who had been treated with ZOL were enrolled in this retrospective cohort study. We analyzed the prognostic factors, including serum N-telopeptide of type I collagen (NTX) levels, as bone metabolism markers. RESULTS: The median overall survival (OS) time was 11.5 months. Child-Pugh grade A (P = 0.004) and intrahepatic tumor stage (IHTS) T0-3 (P = 0.010) correlated significantly with favorable OS. In 46 patients with grade A and T0-3, receiver operating characteristic curve analysis defined 16 nmol BCE/L serum NTX as the cut-off level for median OS. Multivariate analysis identified baseline serum NTX <16 nmol BCE/L (P = 0.045) as the only significant and independent determinant of OS. CONCLUSION: Low baseline serum NTX level correlated with favorable outcome in bone metastatic HCC patients with Child-Pugh grade A and IHTS T0-3 treated with ZOL.

14.
Hepatol Res ; 47(8): 767-772, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27591427

RESUMO

AIM: FibroScan is a tool for the non-invasive diagnosis of hepatic fibrosis. Previous studies have compared liver stiffness to percutaneous liver biopsy findings, but no study has compared liver stiffness to liver resection specimen findings. The aim of this study was to compare FibroScan measurements to resected liver specimen findings. METHODS: From April 2011 to November 2015, a total of 114 patients with liver tumor and hepatitis C were enrolled. We divided them into two groups, the training set and validation set. Liver stiffness was measured by FibroScan before surgery, and specimens obtained by liver resection were evaluated according to the METAVIR system. RESULTS: Using Spearman's rank correlation analysis, a positive correlation between liver stiffness measurement and liver fibrosis stage was observed (r = 0.786, P ≤ 0.0001). In the training set, the area under receiver operating curves for diagnosis of F ≥ 2 was 0.971 (95% confidence interval, 0.928-1.000; cut-off value, 5.9), for diagnosis of F ≥ 3 was 0.911 (0.825-0.997, 9.8), and for diagnosis of F = 4 was 0.917 (0.849-0.985, 15.5). In the validation set, at a cut-off value of 5.9 kPa, sensitivity, specificity, positive predictive values, and negative predictive values for F ≥ 2 were 95.7%, 0.0%, 97.8%, and 0.0%, respectively, of 9.8 kPa for F ≥ 3 were 86.2%, 52.6%, 73.5%, and 71.4%, and of 15.5 kPa for F = 4 were 100%, 71.8%, 45.0%, and 100%. CONCLUSIONS: The stage of stiffness graded by FibroScan has a good correlation with the liver fibrosis of resected liver specimens. It has the ability to diagnose fibrosis stage non-invasively.

15.
Hepatol Res ; 46(13): 1402-1408, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26988002

RESUMO

We report a 60-year-old male patient who developed extrahepatic metastases in bone, peritoneum, and lymph nodes (confirmed by computed tomography and positron emission tomography-computed tomography) after hepatectomy for hepatocellular carcinoma. He was treated with sorafenib (800 mg/day) but developed grade 3 hand-foot syndrome. He continued to be treated with sorafenib but at a lower dose (400 mg/week). The response to sorafenib therapy was graded as complete response at 6 months by the Response Evaluation Criteria in Solid Tumors. Sorafenib was continued for 8 months and the patient remained in complete response for 11 months. Further reporting of similar cases should help design treatment strategies and evaluate predictors of the response to sorafenib therapy.

16.
J Comput Assist Tomogr ; 40(4): 524-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26966955

RESUMO

OBJECTIVES: This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). METHODS: We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. RESULTS: Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. CONCLUSIONS: F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Microvasos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Feminino , Fluordesoxiglucose F18 , Humanos , Japão/epidemiologia , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Cuidados Pré-Operatórios/estatística & dados numéricos , Prevalência , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade
17.
Hepatol Res ; 46(12): 1256-1263, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26916827

RESUMO

AIM: Polymorphisms in the ITPA gene influence anemia during peg-interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with simeprevir, PEG-IFN, and RBV are not sufficiently known. METHODS: We analyzed 212 patients with genotype 1 chronic hepatitis C, who were treated with simeprevir plus PEG-IFN/RBV triple therapy, and assessed the effect of the ITPA polymorphism on hemoglobin levels and RBV dose reduction. ITPA (rs1127354) and IFNL4 (ss469415590) polymorphisms were genotyped using the Invader assay. A stepwise multivariate regression analysis was carried out to identify factors associated with outcome of the therapy. RESULTS: Reduction of hemoglobin levels was similar between patients treated with simeprevir plus PEG-IFN/RBV and those treated with PEG-IFN/RBV therapy. In simeprevir plus PEG-IFN/RBV-treated patients, decreases in hemoglobin levels were faster and greater, and the cumulative proportion of patients with ribavirin dose reduction was significantly greater in ITPA genotype CC patients than in CA/AA patients. The total dose of simeprevir and PEG-IFN was similar between ITPA genotype CC and CA/AA patients. In contrast, the total dose of RBV was lower in patients with the CC genotype. Multivariate analysis showed that the IFNL4 TT/TT genotype, but not the ITPA SNP genotype, treatment history (treatment-naive or relapse during prior treatment), and treatment completion were significantly associated with outcome of therapy. CONCLUSION: ITPA polymorphism influences hemoglobin levels and incidence of RVB dose reduction during simeprevir triple therapy, indicating the importance of monitoring anemia during treatment, particularly for ITPA genotype CC patients.

18.
Hiroshima J Med Sci ; 65(2): 25-33, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29989682

RESUMO

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the a-fetoprotein (AFP) and des-y-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Artéria Hepática , Neoplasias Hepáticas/tratamento farmacológico , Precursores de Proteínas/sangue , Critérios de Avaliação de Resposta em Tumores Sólidos , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Protrombina , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Hepatol Res ; 46(9): 944-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26613201

RESUMO

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct-acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV-related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.

20.
J Gastroenterol Hepatol ; 31(5): 1009-15, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26584407

RESUMO

BACKGROUND: We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study. METHODS: We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013. RESULTS: During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P < 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P < 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P < 0.0001) as significant and independent risk factors for post-SVR HCC. CONCLUSIONS: Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Neoplasias Hepáticas/virologia , Resposta Viral Sustentada , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Distribuição de Qui-Quadrado , Criança , Feminino , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto Jovem , alfa-Fetoproteínas/análise
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