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1.
Medicine (Baltimore) ; 100(42): e27576, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678902

RESUMO

RATIONALE: Various treatments are available for treating hepatocellular carcinoma (HCC). The immune checkpoint inhibitor combination of atezolizumab plus bevacizumab was recently approved for the treatment of unresectable HCC, but there are few reports on the failure of the combination treatment. Here, we present a case of unresectable HCC with adrenal metastasis that was eventually operated on after lenvatinib (LEN) treatment that followed failed treatment with atezolizumab plus bevacizumab. PATIENT CONCERNS: A 68-year-old man was diagnosed with non-alcoholic steatohepatitis-based HCC with adrenal metastasis. DIAGNOSIS: Cirrhosis was classified as Child-Pugh score of 5. HCC was diagnosed as Barcelona Clinic Liver Cancer stage C. INTERVENTIONS: We initiated treatment with atezolizumab plus bevacizumab. Liver dysfunction appeared 2 days after the first administration but was improved by intravenous rehydration and did not appear after the second course. The HCC shrank, but the adrenal metastasis grew bigger after the fourth course, so we changed the therapy to LEN. After HCC and adrenal metastasis were necrotic by LEN, conversion surgery was performed. OUTCOMES: After successful conversion therapy, the general condition of the patient was good, and has been carefully followed for 4 months to date without any evidence of further recurrences. LESSONS: This case showed that even if atezolizumab plus bevacizumab is not effective, multidisciplinary treatment such as LEN and conversion surgery is possible. Given the efficacy of LEN after atezolizumab plus bevacizumab, it is important to consider that there is a possibility of cure even when first-line treatment is not effective for a patient with unresectable HCC.

2.
BMC Gastroenterol ; 21(1): 306, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332532

RESUMO

BACKGROUND: We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. METHODS: The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. RESULTS: NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5-60.3%: P = 0.008), hypertension (48.5-57.4%: P = 0.047), and hyperlipidemia (39.2-53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37-3.61: P = 0.026) and the median platelet count increased (15.1-17.9 × 104/µL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. CONCLUSIONS: The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Humanos , Incidência , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia
3.
Am Surg ; : 31348211041562, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34455865

RESUMO

BACKGROUND: Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. METHODS: This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. RESULTS: Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history (P < .001), and preoperative hemoglobin level (P = .007) were related to HCC development, and the presence of HCC history (P = .002) and preoperative hemoglobin level (P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). DISCUSSION: The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

4.
Cancers (Basel) ; 13(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34439111

RESUMO

The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37-649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.

5.
Intern Med ; 60(13): 2047-2053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193774

RESUMO

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Piridinas , Sorafenibe/uso terapêutico
6.
Clin J Gastroenterol ; 14(5): 1517-1524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34291386

RESUMO

The overall survival of patients with advanced hepatocellular carcinoma with tumor thrombosis of the main trunk or bilobar branches of the portal vein is extremely poor. Moreover, there is no standard treatment established for the condition. Herein, we present the case of a 65-year-old man who were treated the patient with hepatic arterial infusion chemotherapy, radiation therapy for tumor thrombosis, portal vein stent placement, lenvatinib administration, and renal venous shunt embolization. A complete response was observed according to mRECIST and the patient has been alive for 14 months since treatment initiation with no tumor recurrence.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Masculino , Recidiva Local de Neoplasia , Veia Porta , Trombose/etiologia , Trombose/terapia
7.
J Viral Hepat ; 28(9): 1304-1311, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34105859

RESUMO

While the preS1 region of the large hepatitis B surface protein plays an essential role in hepatitis B virus (HBV) infection, the effect of preS1 on liver fibrosis and hepatocarcinogenesis in chronic hepatitis B (CHB) patients is not well known. In this study, we measured serum preS1 levels by chemiluminescent immunoassay technology in 690 CHB patients and evaluated the correlation between serum preS1 levels and HBV, liver function markers and liver inflammation, fibrosis assessed by histological findings. Predictive factors for hepatocellular carcinoma (HCC) development in patients who had no previous history of HCC at the time of preS1 level measurement were also analysed. Median hepatitis B surface antigen (HBsAg) and preS1 levels were 3.08 log IU/mL and 98 ng/mL, respectively. PreS1 values were significantly correlated with serum HBsAg (p <0.001), hepatitis B core-related antigen (HBcrAg) (p <0.001) and HBV DNA levels (p <0.01). PreS1 values were also significantly correlated with serum alanine aminotransferase levels (p <0.001) and were significantly higher in patients who had higher grading of liver inflammatory activity (p <0.05). HBsAg level was correlated, but preS1/HBsAg ratio reflected liver fibrosis staging more directly than HBsAg alone. Multivariate analysis identified age ≥53 years (hazard ratio [HR], 18.360 for <53 years; p = 0.021) and preS1/HBsAg ratio ≥0.12 (HR, 6.205 for <0.12; p = 0.040) as significant and independent factors for HCC development in CHB patients. The preS1/HBsAg ratio directly reflects liver fibrosis, and the ratio might be a predictive marker for HCC development in CHB patients.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , DNA Viral , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Pessoa de Meia-Idade
8.
BMC Cancer ; 21(1): 668, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090354

RESUMO

BACKGROUND: Patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) intermediate stage hepatocellular carcinoma (HCC) encompass a broad clinical population. Kinki criteria subclassifications have been proposed to better predict prognoses and determine appropriate treatment strategies for these patients. This study validated the prognostic significance within the Kinki criteria substages and analyzed the role of liver resection in patients with intermediate stage HCC. METHODS: Patients with intermediate stage HCC (n = 378) were retrospectively subclassified according to the Kinki criteria (B1, n = 123; B2, n = 225; and B3, n = 30). We analyzed the overall survival (OS) and treatment methods. RESULTS: The OS was significantly different between adjacent substages. Patients in substage B1 who underwent liver resection had a significantly better prognosis than those who did not, even after propensity score matching (PSM). Patients in substage B2 who underwent liver resection had a significantly better prognosis than those who did not; however, there was no difference after PSM. There was no difference in prognosis based on treatments among patients in substage B3. CONCLUSIONS: The Kinki criteria clearly stratify patients with intermediate stage HCC by prognosis. For substage B1 HCC patients, liver resection provides a better prognosis than other treatment modalities. In patients with substage B2 and B3, an alternative approach is required.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/estatística & dados numéricos , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Cisplatino/administração & dosagem , Feminino , Seguimentos , Humanos , Óleo Iodado/administração & dosagem , Estimativa de Kaplan-Meier , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Sorafenibe/administração & dosagem , Resultado do Tratamento
9.
Cancers (Basel) ; 13(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067075

RESUMO

Few studies exist on the relationship between post-progression survival (PPS) and skeletal muscle volume in hepatocellular carcinoma (HCC) patients receiving sorafenib. This study aimed to analyze the effects of muscle volume on clinical outcomes. We retrospectively enrolled 356 HCC patients. Various clinical parameters, including skeletal muscle index, were analyzed as predictors of overall survival (OS), progression-free survival (PFS), and PPS. Patients with high muscle volume showed longer survival or PPS than those with low muscle volume (median survival time: 12.8 vs. 9.5 months, p = 0.005; median PPS: 8.2 vs. 6.3 months, p = 0.015); however, no differences in PFS were found. Multivariate analysis indicated that muscle volume was an independent predictor of PPS and OS. Skeletal muscle volume was a PPS predictor in HCC patients receiving sorafenib. Therefore, survival can be prolonged by the upregulation of skeletal muscle volume, especially in HCC patients with skeletal muscle depletion.

10.
J Exp Clin Cancer Res ; 40(1): 215, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174931

RESUMO

BACKGROUND: There has been a recent surge in interest in predicting biological effects associated with genomic alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN). METHOD: We retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele frequencies (VAFs) during treatment and clinical outcome were evaluated. RESULTS: In total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes were TP53 (54%), CTNNB1 (42%), TERT (42%), ATM (25%), and ARID1A (13%). The reduction in the mean frequency of variants (VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity and sensitivity of the reduction of VAFmean for predicting partial response were 0.67 and 1.0, respectively, which were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the mutation status at baseline and the effectiveness of LEN was observed. CONCLUSION: Our study demonstrated that somatic alterations could be detected in the majority of advanced HCC patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in clinical practice.

11.
Medicine (Baltimore) ; 100(26): e26436, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190166

RESUMO

ABSTRACT: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG.


Assuntos
Cirurgia Bariátrica/métodos , Gastrectomia/métodos , Testes de Função Hepática/métodos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biópsia/métodos , Índice de Massa Corporal , Feminino , Humanos , Japão/epidemiologia , Laparoscopia/métodos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Indução de Remissão , Tempo
12.
Liver Cancer ; 10(2): 151-160, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33977091

RESUMO

Background: Overall survival of patients with advanced hepatocellular carcinoma (HCC) with Vp4 (tumor thrombosis of the main trunk or bilobar of the portal vein) is extremely poor. Purpose: The purpose of this study is to clarify the prognosis of hepatic arterial infusion chemotherapy (HAIC) combined with radiation therapy (RT) for advanced HCC with Vp4 and to analyze the factors that contribute to the prognosis. Methods: In this retrospective cohort study, 51 HCC patients who were treated with HAIC and RT for portal vein tumor thrombosis and met the following criteria were enrolled: (i) with Vp4; (ii) Child-Pugh score of 5-7; (iii) Eastern Cooperative Oncology Group performance status of 0 or 1; (iv) no history of systemic therapy; and (v) from September 2004 to April 2019. Results: Median overall survival and median progression-free survival were 12.1 and 4.2 months, respectively. Multivariate analysis showed >50% of relative tumor volume in the liver (HR, 3.027; p = 0.008) and extrahepatic spread with (HR, 3.773; p = 0.040) as significant and independent factors of OS. The total overall response rate (ORR) was 19.6%; ORR in main tumor was 13.7%; and ORR in Vp4 was 51.0%. None of the patients who received HAIC combined with RT for advanced HCC with Vp4 developed hepatic failure. This combination therapy of HAIC with RT was safe and well tolerated in all cases. Conclusion: Combination therapies of HAIC and RT might be good therapy for advanced HCC with Vp4.

13.
Biochem Biophys Res Commun ; 559: 78-83, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33932902

RESUMO

Combination therapy with glecaprevir and pibrentasvir (PIB) has high efficacy for patients with hepatitis C virus (HCV) infection except among those who experienced NS5A-P32 deletion (del) mutation during prior DAA treatment failure. However, some patients fail to achieve SVR through combination treatment even in the absence of NS5A-P32del. We analyzed emergence of NS5A resistance-associated substitutions (RASs) against PIB using HCV-infected mice. Male human hepatocyte transplanted mice were infected with genotype 1b wild-type HCV. Mice were treated with PIB, resulting in a transient decrease in serum HCV RNA levels but followed by relapse during the treatment. Direct sequence analysis showed emergences of various mutations in the NS5A region, including L31V/P32del, L31F/P32del/Y93H, NS5A-P29del/Y85C, and NS5A-F37Y. PIB was less effective in mice with NS5A-F37Y mutations compared to mice with wild-type HCV. NS5A-F37Y showed 5.4-fold resistance to PIB relative to wild-type based on analysis using HCV subgenomic replicon systems. The present in vivo and in vitro studies identified NS5A-F37Y as a novel RAS against PIB and showed the possibility of emergence of various NS5A RASs including P29del, P32del and F37Y following PIB treatment. These mutations might emerge and lead to failure to respond to DAA therapies including PIB-based regimens in chronic hepatitis C patients.


Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , Farmacorresistência Viral , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Pirrolidinas/farmacologia , Animais , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Hepacivirus/genética , Hepatite C/virologia , Hepatócitos/virologia , Humanos , Masculino , Camundongos , Camundongos SCID , Mutação/efeitos dos fármacos , Pirrolidinas/uso terapêutico
14.
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
15.
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
16.
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
17.
IDCases ; 23: e01059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552903

RESUMO

Background: Multi-virus real-time polymerase chain reaction (PCR) system is able to simultaneously detect 163 viruses using a multiplex Taqman real-time PCR system. We present a case of acute liver failure (ALF) of unknown etiology diagnosed with echovirus 30 infection via multi-virus real-time PCR. Case presentation: A previously healthy 66-year-old man had a persistent fever and developed ALF of unclear etiology. Although viral infection was suspected, serological screening showed no evidence of acute viral infections such as hepatitis A, B, C and E, Epstein-Barr virus, herpes simplex virus, and varicella zoster virus. Multi-virus real-time PCR revealed the presence of enterovirus and echovirus 30 genomes, and reverse transcription-PCR using enterovirus-specific primers confirmed the presence of enterovirus genome in serum samples at the time of admission. Anti-echovirus antibody titers showed an increase in paired sera. In spite of multimodality treatment, the patient died due to multiple organ failure. Histological analysis in autopsy revealed extensive coagulative necrosis of the hepatocytes and immunohistochemical analysis showed the expression of enterovirus antigens in necrotic hepatocytes. Conclusions: We present here a case of echovirus 30 associated with ALF. Multi-virus real-time PCR is useful for detection of virus for patients with ALF of unknown etiology suspected of harboring a viral infection.

18.
J Gastroenterol ; 56(2): 181-190, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33392749

RESUMO

BACKGROUND: To evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced hepatocellular carcinoma (HCC) who had progressed following one or two lines of systemic therapy including sorafenib. An exploratory evaluation in sorafenib-naïve patients was performed. METHODS: In this open-label, single-arm, phase 2 trial, patients received oral cabozantinib 60 mg once daily. The primary endpoint was progression-free survival (PFS) rate at Week 24. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR, best response of complete/partial response), disease control rate (DCR, objective response or stable disease) and safety. RESULTS: Thirty-four patients received cabozantinib across 17 centers (prior sorafenib cohort, n = 20; sorafenib-naïve cohort, n = 14). PFS rate at 24 weeks was 59.8% [90% confidence interval (CI) 36.1-77.2%] in the prior sorafenib cohort, 16.7% (90% CI 4.0-36.8%) in the sorafenib-naïve cohort and 40.1% (90% CI 24.8-55.0%) overall. Median PFS was 7.4 months for the prior sorafenib cohort, 3.6 months for the sorafenib-naïve cohort, and 5.6 months overall. OS rate at 6 months was 100.0%, 78.6% and 91.1%, respectively; DCR was 85.0%, 64.3% and 76.5%, respectively. The ORR was 0.0% for both cohorts. All patients required dose modifications due to adverse events, the most common of these were palmar-plantar erythrodysesthesia syndrome and diarrhea. Three patients (8.8%) discontinued due to adverse events other than disease progression. CONCLUSIONS: Cabozantinib 60 mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration: NCT03586973).

19.
Dig Dis Sci ; 66(4): 1268-1275, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32436125

RESUMO

BACKGROUND: Serum IgG4 level is a useful diagnostic marker for autoimmune pancreatitis (AIP), but it is difficult to use to predict relapse. AIMS: We investigated whether serum autotaxin (ATX) level is predictive of AIP relapse after steroid therapy. METHODS: Fifty-six patients with type 1 AIP were investigated. We measured serum ATX at the time of diagnosis. We selected 24 males for whom serum samples during steroid therapy had been obtained and measured serum ATX at steroid therapy for induction of remission and at maintenance therapy. In the relapse group, we also measured ATX at the time of relapse. RESULTS: ATX was significantly higher in female patients than in male patients. In order to clarify changes in ATX during steroid therapy, we focused on 24 male patients. We found that ATX decreased significantly during steroid therapy for induction of remission and at the time of maintenance therapy. In half of all patients who relapsed during maintenance therapy, ATX was significantly elevated at the time of relapse compared with that of induction therapy (P = 0.039). When we compared ATX at the time of maintenance therapy between patients with relapse and without, we observed significantly higher ATX in the former (P = 0.024). We found that the combination of ATX and elastase-1 could predict relapse with high accuracy (95%). CONCLUSIONS: Preliminary evidence suggests that serum ATX might serve as a candidate biomarker to predict relapse of AIP as well as to monitor the effect of steroid therapy.

20.
Digestion ; 102(2): 188-196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31574519

RESUMO

INTRODUCTION: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. METHODS: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. RESULTS: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. CONCLUSIONS: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.

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