RESUMEN
BACKGROUND AND AIMS: Real-time tissue elastography is a non-invasive method for measuring liver elasticity. However, there are no reports evaluating the value of real-time tissue elastography for liver fibrosis in hepatitis C virus-infected patients with sustained virological response. The aim of this study is to clarify the diagnostic performance of real-time tissue elastography in patients with sustained virological response. METHODS: In this prospective study, we enrolled 425 chronic hepatitis C patients who underwent liver biopsy: 118 patients with sustained virological response (45.8% women) and 307 patients with hepatitis C virus (51.1% women). The post-sustained virological response biopsy was performed 5.9 ± 1.8 years after the therapy. Liver fibrosis index measurements as assessed using real-time tissue elastography were performed on the same day of biopsy. RESULTS: The respective mean liver fibrosis index values for fibrosis stages F0, F1, F2, F3, and F4 were 2.82 ± 0.33, 2.90 ± 0.51, 3.06 ± 0.58, 3.65 ± 0.24, and 3.83 ± 0.65, respectively, in patients with sustained virological response. The diagnostic accuracies expressed as areas under the receiver operating characteristic curves in patients with sustained virological response were 0.776 for the diagnosis of significant fibrosis (≥F2), 0.885 for severe fibrosis (≥F3), and 0.860 for cirrhosis (F4), respectively. The optimum cut-off values liver fibrosis index were 3.14 for ≥F2, 3.24 for ≥F3, and 3.30 for F4 in patients with sustained virological response. CONCLUSION: Real-time tissue elastography is an acceptable method for predicting the severity of fibrosis in hepatitis C virus patients with sustained virological response.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica , Cirrosis Hepática , Anciano , Biopsia , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Respuesta Virológica SostenidaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. METHODS: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. RESULTS: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). CONCLUSION: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.
Asunto(s)
Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Tegafur/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Neoplasias Pancreáticas/mortalidad , Retratamiento , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: The effect of skeletal muscle fat deposition on the prognosis of patients with chronic liver disease remains unclear. Skeletal muscle fat deposition can be estimated by attenuation of skeletal muscle in Hounsfield units (HU) on computed tomography (CT). The aim of this retrospective cohort study was to investigate the association between skeletal muscle fat deposition assessed by skeletal muscle attenuation (SMA), and hepatocellular carcinoma (HCC). METHODS: We enrolled 288 patients with chronic liver disease (139 men, 149 women; mean age 67.5 ± 10.4 y; hepatitis C virus, 239; hepatitis B virus, 17; without viral infection, 32; chronic hepatitis, 227; and cirrhosis, 61) who underwent liver biopsy and CT scanning between January 2013 and February 2017. The patients were divided into two groups based on SMA levels, with the cutoff value of 31 HU. We analyzed the effect of SMA on HCC development. RESULTS: During the study follow-up period (median, 2.50 y; range, 0.5-4.7 y), HCC was identified in 19 patients (7%). The cumulative incidence of HCC in patients with lower SMA (<31 HU) was significantly higher than in patients with SMA ≥31 HU (P = 0.007). Cox proportional hazards regression analysis confirmed cirrhosis (hazard ratio [HR], 6.626; 95% confidence interval [CI], 2.57-17.12; P <0.001) and lower SMA (HR, 3.502; 95% CI, 1.25-9.83; P = 0.017) as significant independent factors associated with HCC development in patients with chronic liver disease. CONCLUSIONS: Patients with cirrhosis and skeletal muscle fat deposition assessed by SMA had a higher risk for developing HCC.
Asunto(s)
Tejido Adiposo/patología , Carcinoma Hepatocelular/etiología , Enfermedad Hepática en Estado Terminal/patología , Neoplasias Hepáticas/etiología , Músculo Esquelético/patología , Tejido Adiposo/diagnóstico por imagen , Anciano , Carcinoma Hepatocelular/epidemiología , Enfermedad Hepática en Estado Terminal/complicaciones , Femenino , Estudios de Seguimiento , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Hepatitis Crónica/complicaciones , Hepatitis Crónica/patología , Humanos , Incidencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND AND AIMS: Pruritus is one of the complications with chronic liver disease and markedly worsens quality of life. However, the current status of pruritus in chronic hepatitis C patients who have achieved a sustained virological response (SVR) has not been clarified sufficiently. The aim of this study was to investigate the predictors of pruritus in post-SVR patients treated with direct-acting antivirals (DAA). PATIENTS AND METHODS: In this retrospective study, we enrolled 110 hepatitis C patients with SVR who underwent serial shear wave elastography before DAA therapy and at the end of treatment. The severity of pruritus was evaluated using Kawashima's pruritus scores and a visual analog scale. RESULTS: The prevalence of pruritus before treatment and after SVR was 28.2 and 25.5%. Multivariate logistic regression analysis confirmed that a history of hepatocellular carcinoma [odds ratio (OR): 9.72; 95% confidence interval (CI): 2.05-46.15; P=0.004], high γ-glutamyl transpeptidase levels at baseline (OR: 5.77; 95% CI: 1.83-18.21; P=0.003), low serum albumin at the end of treatment (OR: 4.85; 95% CI: 1.31-17.99; P=0.018), and high liver stiffness measurement assessed by shear wave elastography at the end of treatment (OR: 3.16; 95% CI: 1.19-11.01; P=0.024) were significant independent factors associated with pruritus in patients who had achieved an SVR following DAA therapy. CONCLUSIONS: In chronic hepatitis C patients with SVR after DAA therapy, the incidence of pruritus is not uncommon. Liver stiffness measurement is useful for predicting the incidence of pruritus. Thus, even if SVR is achieved, patients with higher liver stiffness at the end of treatment must be monitored carefully for pruritus.
Asunto(s)
Antivirales/uso terapéutico , Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/tratamiento farmacológico , Prurito/epidemiología , Respuesta Virológica Sostenida , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Femenino , Hepatitis C Crónica/epidemiología , Humanos , Incidencia , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Prurito/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Severe muscle volume loss is a recognized negative prognostic factor in patients with chronic liver disease. However, the effect of skeletal muscle fat deposition, referred to as myosteatosis on muscle volume loss remains unclear. The aim of this study was to investigate the relationships between myosteatosis and skeletal muscle volume loss. METHODS: We enrolled 362 patients with chronic liver disease (186 men, 176 women; mean age 68.4 ± 10.0 years, 94 with cirrhosis) who underwent liver biopsy and computed tomography scanning between January 2013 and February 2017. A transverse computed tomography image of each scan at the third lumbar vertebra was used to evaluate skeletal muscle tissues. RESULTS: Prevalence of skeletal muscle volume loss and myosteatosis were 36% and 82%, respectively. Of those with skeletal muscle volume loss, 93% have concomitant myosteatosis. Univariate analysis revealed that higher age, female, lower body mass index (BMI), higher serum albumin, lower alanine aminotransferase (ALT), lower gamma-glutamyl transpeptidase, lower total bilirubin, lower α-fetoprotein, lower skeletal muscle attenuation, and liver steatosis were significantly associated with skeletal muscle volume loss. Multivariate logistic regression analysis confirmed that lower BMI (odds ratio [OR] 5.26, 95% confidence interval [CI], 3.21-8.54; P < 0.001), presence of myosteatosis (OR, 2.82; 95% CI, 1.26-6.30; P < 0.001), lower ALT (OR, 2.04; 95% CI, 1.18-3.52; P = 0.010), and female (OR, 1.71; 95% CI, 1.04-2.28; P = 0.034) were significant independent factors associated with skeletal volume loss. CONCLUSIONS: Myosteatosis, low BMI, low ALT, and female are associated with skeletal muscle volume loss in patients with chronic liver disease.
RESUMEN
BACKGROUND AND AIM: The aim of this study is to elucidate the natural history of pancreatic cystic lesions (PCLs), including branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN), via midterm follow-up analysis of a multicenter prospective observational study (NSPINAL study). METHODS: From July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with > 12 months of follow up were analyzed. Every patient was asymptomatic, and endoscopic ultrasound was performed at the initial diagnosis to exclude high-risk individuals. Follow up included endoscopic ultrasound, computed tomography, or magnetic resonance imaging at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated. RESULTS: The 664 patients (358 men) were followed for a median of 33.5 months (interquartile range 29). The cyst and main pancreatic duct sizes were 16.6 ± 9.3 and 2.3 ± 1.0 mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety-six patients (14.5%) showed worsening progression on imaging. There were two resectable and four unresectable cases of pancreatic ductal adenocarcinoma and three cases of malignant BD-IPMN. The 3-year risk of developing PC was 1.2%. The standardized incidence ratio for PC among PCLs was 10.0 (95% confidence interval 3.5-16.5), and the standardized incidence ratio among BD-IPMN was 16.6 (95% confidence interval 5.1-28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC. CONCLUSIONS: Malignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect pancreatic ductal adenocarcinoma at early stages.
Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/etiología , Quiste Pancreático/complicaciones , Quiste Pancreático/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/etiología , Medición de Riesgo , Anciano , Carcinoma Ductal Pancreático/patología , Diagnóstico por Imagen , Progresión de la Enfermedad , Detección Precoz del Cáncer , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Quiste Pancreático/patología , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Riesgo , Factores de TiempoRESUMEN
BACKGROUND & AIMS: We investigated the correlation between histological characteristics and changes in liver stiffness (LS) in patients with sustained virological response (SVR) using acoustic radiation force impulse (ARFI) elastography. METHODS: In this prospective study, we enrolled 176 hepatitis C patients with SVR who underwent ARFI elastography and liver biopsy before antiviral treatment, and serial ARFI elastography at the end of treatment (EOT) and at 24 weeks after the EOT. To compare the long-term changes in LS in patients with SVR using ARFI elastography, another group of 140 patients who had undergone paired biopsy after achieving SVR was included. RESULTS: Mean LS values were 1.60±0.63 m/s, 1.48±0.56 m/s and 1.37±0.62 m/s at baseline, EOT and 24 weeks after EOT, respectively, P<.001. Higher inflammatory activity at baseline was associated with an improvement in LS at the EOT, with an odds ratio of 1.940. Significant fibrosis at baseline was associated with an improvement in LS at 24 weeks after the EOT, with an odds ratio of 2.617. Among patients in the paired biopsy group with baseline fibrosis stage identical to the ARFI group, LS values at 24 weeks after the EOT did not show any difference with values at 5 years after EOT. CONCLUSIONS: Pre-treatment histological characteristics influence LS reduction after SVR is achieved.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Hepatitis C/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Hígado/diagnóstico por imagen , Respuesta Virológica Sostenida , Anciano , Antivirales/uso terapéutico , Biopsia , Femenino , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Hígado/efectos de los fármacos , Hígado/virología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC). METHODS: Chemo-naïve patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]. The secondary end points were to evaluate toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: From March 2012 to February 2015, 14 patients from seven different institutions were enrolled in the study, and 13 cases were evaluable for assessment. Eleven cases (84.6%) had distant metastases, and 8 cases (61.5%) had obstructive jaundice. There was no CR, 1 PR (7.7%), 11 SD (84.6%), and 1 progressive disease (PD) (7.7%). The RR was 7.7%, whereas the DCR was 92.3%. The median PFS was 3.1 months, the median OS was 6.2 months, and the one-year survival rate was 0%. Grade 3 hematologic toxicity was observed in three cases (23%), but all of them recovered upon drug withdrawal, and there was no treatment-related death. CONCLUSION: Although gemcitabine plus cisplatin has a high DCR (92.3%) and relatively low toxicity, the RR is less than 10%, and development of new therapies is desired for the treatment of unresectable GBC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Neoplasias de la Vesícula Biliar/patología , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) in patients with chronic hepatitis C can develop after sustained virological response (SVR) to antiviral therapy for HCV, that is, the eradication of HCV, and effective surveillance systems for HCC should be established for this population. We retrospectively evaluated the utility of three laboratory liver fibrosis indices (aspartate aminotransferase-platelet ratio index [APRI], FIB-4 index and Forns index) for identifying patients at low risk of HCC development after SVR, for whom the termination of surveillance for HCC can be considered. METHODS: APRI, FIB-4 index and Forns index scores were calculated based on laboratory data prior to anti-HCV therapy and at 24 weeks after the end of anti-HCV therapy (SVR24) in 522 patients with SVR who continued surveillance for HCC after SVR. The associations between HCC development and laboratory indices at both points were analysed. RESULTS: Twenty-one patients developed HCC after SVR during 2.3-24.4 years follow-up. Whereas HCC developed even in patients with low APRI or FIB-4 index scores, no patients with low Forns index scores developed HCC after SVR. These results were confirmed in a separate cohort of 309 patients who achieved SVR (HCC developed in 17 patients during 1.7-21.6 years follow-up). CONCLUSIONS: Forns index, especially assessed prior to anti-HCV therapy, was a useful laboratory liver fibrosis index for identifying patients at low likelihood of HCC after SVR. This index may be used as one of indicators to consider the termination of surveillance for HCC after the eradication of HCV.
Asunto(s)
Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Adulto , Factores de Edad , Anciano , Antivirales/uso terapéutico , Biomarcadores , Biopsia , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Incidencia , Cirrosis Hepática/etiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Predictive factors for hepatocarcinogenesis following eradication of hepatitis C virus by direct-acting antivirals (DAAs) are unknown. The aim of the study was to investigate the relationships between liver stiffness (LS) using acoustic radiation force impulse (ARFI) erastograghy and the development of hepatocellular carcinoma (HCC) in patients who achieved sustained virological response (SVR) treated with DAA. METHODS: In this prospective study, we enrolled 263 hepatitis C patients with SVR who underwent ARFI before DAA treatment. Thirty patients had previous HCC. RESULTS: The median LS value according to ARFI measurements was 1.34 m/s (range: 0.67-4.35). During the follow-up period (median: 18.1 months), development of HCC occurred in 19 patients (7.2%; HCC occurrence in 7 patients and HCC recurrence in 12 patients). By multivariate Cox regression analysis, HCC history (hazard ratio [HR]: 10.634; 95% confidence interval [CI]: 4.13-27.37; P = 0.001), older age (HR: 4.638; 95% CI: 1.63-13.61; P = 0.004) and higher total bilirubin levels (HR: 4.189; 95% CI: 1.66-10.60; P = 0.002) were independent predictors for the development of HCC, and higher LS value (≥1.73 m/s) at baseline was an independent predictor for HCC occurrence (HR: 8.350; 95% CI: 1.62-43.09; P = 0.011). The cumulative recurrence of HCC was statistically similar according to the degree of LS in patients who were previously treated for HCC. CONCLUSION: The LS value at baseline is useful for predicting HCC occurrence. Thus, even if SVR is achieved, patients with higher LS at baseline must be followed carefully for HCC occurrence.
RESUMEN
BACKGROUND AND AIMS: Eradicating chronic hepatitis C virus (HCV) infection improves liver fibrosis and reduces hepatocellular carcinoma (HCC) incidence in chronic HCV patients. We evaluated the relationship between fibrosis regression, as assessed by sequential biopsies, and clinical factors of patients with sustained virological response (SVR). METHODS: We retrospectively enrolled 130 patients (74 men; 60.1 ± 8.1 years) with chronic HCV treated with interferon and ribavirin therapy who achieved SVR. To evaluate the change in fibrosis stage over time, all patients underwent a pre-therapy initial biopsy and a second biopsy after achieving SVR. RESULTS: The mean time between biopsies was 5.5 ± 1.2 years. Fibrosis stage regressed in 55 patients (42.3%), remained stable in 69 (53.1%), and progressed in 6 (4.6%). The mean fibrosis stage significantly decreased, from 2.01 ± 0.99 units to 1.61 ± 1.24 units (P < 0.001). Aspartate aminotransferase, γ-glutamyltransferase, and α-fetoprotein (AFP) levels at 24 weeks after the end of treatment (EOT) were significantly lower, and the platelet count at 24 weeks after the EOT was significantly higher in patients with fibrosis regression than in those without. Logistic regression analysis confirmed that lower AFP levels (< 5.4 ng/mL) at 24 weeks after the EOT (odds ratio [OR], 4.626; 95% confidence interval [CI], 1.557-13.153; P = 0.006) and HCV genotype 2 (OR, 2.198; 95% CI, 1.010-4.786; P = 0.047) were significant independent predictive factors for regressed fibrosis after SVR. CONCLUSIONS: Lower post-treatment AFP levels and HCV genotype 2 significantly correlated with liver fibrosis regression after SVR.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Respuesta Virológica Sostenida , alfa-Fetoproteínas/metabolismo , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Biopsia , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Curva ROC , Inducción de Remisión , Estudios Retrospectivos , Ribavirina/uso terapéutico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Liver fibrosis remains an important risk factor for hepatocarcinogenesis in patients with chronic hepatitis C even after the eradication of hepatitis C virus (HCV). However, it is difficult to estimate liver fibrosis based on liver biopsy after the eradication of HCV. We investigated the ability of laboratory indices to predict liver fibrosis in patients with sustained virologic response (SVR) to antiviral therapy. Three laboratory liver fibrosis indices (aspartate aminotransferase-platelet ratio index (APRI), FIB-4 index, and Forns index) were calculated based on data at the time of initial pretreatment liver biopsy and at second liver biopsy performed approximately 5 years after SVR in 115 patients who underwent serial liver biopsies. The indices at the time of initial biopsy were compared to histological degree of liver fibrosis in initial biopsy, and laboratory indices at the time of second liver biopsy were compared to the degree of fibrosis in second biopsy. In both comparisons, there were significant increases in all 3 indices with the increase of liver fibrosis grade as assessed in liver biopsy specimens. All 3 indices at the time of second biopsy were able to predict moderate to advanced (METAVIR score F2-4) and advanced (F3-4) fibrosis on liver biopsy, with the area under the receiver-operating characteristics curve >0.8 and the accuracy >70%. All 3 laboratory indices of fibrosis accurately reflected liver fibrosis in patients with SVR for 5 years despite the normalization of serum liver transaminase activity and the lack of liver inflammation.
Asunto(s)
Hepacivirus , Hepatitis C Crónica , Cirrosis Hepática , Anciano , Biopsia , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Masculino , Persona de Mediana EdadRESUMEN
AIM: Hepatocellular carcinoma develops even in some patients who achieve a sustained virological response following treatment for hepatitis C virus infection. This study investigated the relationship between changes in fibrosis, as assessed by sequential biopsies, and development of hepatocellular carcinoma in patients who achieved a sustained virological response for hepatitis C virus. METHODS: We enrolled 97 patients with sustained virological response who had undergone initial biopsies before therapy and sequential biopsies at an average of 5.8 ± 1.9 years after the initial biopsy. Factors associated with hepatocellular carcinoma were retrospectively analyzed. RESULTS: The liver fibrotic stage regressed in 44 patients (45%), remained stable in 47 patients (48%) and progressed in six patients (6%). The fibrotic stage significantly decreased, from 1.54 ± 0.86 to 1.16 ± 1.07 units. Hepatocellular carcinoma was identified in 12 patients (12.4%). The cumulative incidence of hepatocellular carcinoma in patients with progressive fibrosis was significantly higher than that in patients with regressed or stable fibrosis (P < 0.001). A Cox proportional hazards regression analysis confirmed that progressive fibrosis in sequential liver biopsies (hazard ratio [HR], 8.30; P = 0.001) and low platelet counts before treatment (HR, 8.69; P = 0.006) were significant independent factors associated with the development of hepatocellular carcinoma in patients with a sustained virological response. CONCLUSION: Progressive fibrosis, assessed by sequential biopsies, was significantly correlated with development of hepatocellular carcinoma in patients who had achieved a sustained virological response for hepatitis C virus.
RESUMEN
The chicken Ig-ß locus is organized by three cell-type-specific genes and two ubiquitously expressed genes. B-cell-specific DNase I hypersensitive sites (DHS) in that locus, including three present inside the flanking gene, were grouped into six regions and deleted. The deletions decreased Ig-ß mRNA content to <0.1% of that of normal DT40 cells and converted epigenetic parameters such as histone modifications, CG methylation and DNase I hypersensitivity into inactive states. Knocked-in DHS regions into knock-out cells reactivated both transcription of the Ig-ß gene and epigenetic parameters. Thus, the collaboration of the scattered regulatory regions was essential and sufficient not only for B-cell-specific transcription of the Ig-ß gene, but also for the conversion of epigenetic parameters. On the basis of the knock-in studies, we determined the regions involved in the conversion and maintenance of the epigenetic parameters. These scattered regulatory regions were limited in vicinity such as in an intron of the gene, in the intergenic regions and in the introns of a flanking gene.
Asunto(s)
Pollos/genética , Técnicas de Sustitución del Gen/métodos , Técnicas de Inactivación de Genes/métodos , Inmunoglobulinas/genética , Secuencias Reguladoras de Ácidos Nucleicos , Animales , Linfocitos B/metabolismo , Línea Celular , Pollos/inmunología , Desoxirribonucleasa I/metabolismo , Epigenómica , Transcripción GenéticaRESUMEN
PURPOSE: S-1 is one of the second-line candidate agents for gemcitabine-refractory unresectable pancreatic cancer. Two phase II studies have been reported for second-line chemotherapy with S-1, but these studies did not investigate introduction rate and suitable dose of second-line S-1. Therefore, we conducted a prospective multicenter study in which chemo-naïve patients were enrolled and had two levels of S-1 dose. METHODS: Chemo-naïve patients with unresectable pancreatic cancer were enrolled. This study started with 80 mg/m(2)/day dose of S-1 as second-line chemotherapy and tolerability was checked. When tolerability was not confirmed in initial patients, the dose of S-1 was shifted to 60 mg/m(2)/day. When tolerability was confirmed at 80 or 60 mg/m(2)/day, the study continued, and up to 20 patients were accumulated with the dose. In addition, the introduction rate of second-line S-1 was examined. RESULTS: Six of the initial 7 patients with 80 mg/m(2)/day dose of S-1 completed one course of second-line chemotherapy. Twenty patients were accumulated with an 80 mg/m(2)/day dose of S-1. With the exception of one patient continued gemcitabine chemotherapy, two of the remaining 19 patients withdrew from this study because of toxicity during the period of gemcitabine chemotherapy. Fifteen of the remaining 17 gemcitabine-refractory patients could complete one course of S-1 as second-line chemotherapy with acceptable toxicity. CONCLUSIONS: This prospective multicenter study showed that 15 (78.9%) out of 19 chemo-naïve unresectable pancreatic cancer patients could complete one course of 80 mg/m(2)/day dose of S-1 as second-line chemotherapy after first-line gemcitabine chemotherapy failure with tolerable toxicity.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Adenocarcinoma/patología , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilis/metabolismo , Desoxicitidina/uso terapéutico , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , Páncreas/patología , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Análisis de Supervivencia , Tegafur/efectos adversos , Insuficiencia del Tratamiento , GemcitabinaRESUMEN
AIM: Endoscopic papillary balloon dilatation (EPBD), which allows preservation of papillary functions, is used as the first-line therapy in our hospital for common bile duct (CBD) stones to reduce biliary complications. In the present study, we investigated causal factors for CBD stones and compared long-term prognosis between EPBD and endoscopic sphincterotomy (EST). METHODS: A total of 453 EPBD and 233 EST cases treated between April 1996 and May 2007 were examined. They were categorized into four groups: group 1, gallbladder (GB) with stones was resected after CBD stones were extracted (cholecystectomy for GB with stones); group 2, GB with stones was not resected after CBD stones were extracted (no cholecystectomy for GB with stones); group 3, only CBD stones were extracted while the GB without stones was not resected (GB without stones); and group 4, CBD stones with a history of cholecystectomy (absence of GB). Then, postoperative recurrence of CBD stones was compared. To examine changes in papillary functions by EPBD, Oddi's sphincter pressure was measured before and after EPBD. RESULTS: Recurrence was observed in 31 EPBD and 40 EST cases. When recurrence rates by EPBD/EST were compared among the four treatment groups, they were lower with EPBD than with EST in all groups. Oddi's sphincter functions were preserved by 70% after EPBD. CONCLUSION: Low-pressure EPBD in combination with isosorbide dinitrate enabled preservation of papillary functions by 70%, which would improve a long-term prognosis.
Asunto(s)
Cateterismo , Endoscopía , Cálculos Biliares/terapia , Esfinterotomía Endoscópica , Anciano , Cateterismo/efectos adversos , Endoscopía/efectos adversos , Femenino , Cálculos Biliares/cirugía , Humanos , Dinitrato de Isosorbide/uso terapéutico , Masculino , Persona de Mediana Edad , Pancreatitis/etiología , Pancreatitis/prevención & control , Pronóstico , Recurrencia , Esfinterotomía Endoscópica/efectos adversos , Vasodilatadores/uso terapéuticoAsunto(s)
Vesícula Biliar/anomalías , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomía Laparoscópica , Colecistografía , Femenino , Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/patología , Vesícula Biliar/cirugía , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: To evaluate the imaging possibility of a newly designed electronic radial scanning echoendoscope (ER-ES). METHODS: In the in vivo study of swine, we obtained B-mode endoscopic ultrasonography (EUS) images of the gastric and gallbladder (GB) walls and checked the ability to detect Doppler signals using ER-ES and electronic linear array echoendoscope (EL-ES). Furthermore, in the ex vivo study of swine, B-mode EUS images of fixed gastric and GB wall specimens were obtained using ER-ES, EL-ES and mechanical radial scanning echoendoscope (MR-ES). In the study of resected human specimens, we obtained B-mode EUS images of five resected GB specimens (three normal GB, one cholecystitis and one cancerous) using the three types of echoendoscope. RESULTS: In the in vivo study of swine, ER-ES and EL-ES depicted the gastric walls as five-layered, and the GB walls as single-layered structures. The ability to detect Doppler signals was equal between ER-ES and EL-ES. In the ex vivo study of swine, ER-ES, MR-ES and EL-ES equally delineated the gastric walls as five-layered and GB walls as three-layered structures. In the study of resected human specimens, results demonstrated the normal GB walls as three-layered, the cholecystitis as a combination of outer high-echoic and inner low-echoic layers, and the cancer as a protruded tumor. CONCLUSIONS: We conclude that ER-ES has faculties for making B-mode images as well as EL-ES and MR-ES. In addition, in the in vivo study, ER-ES can analyze blood flow information as well as EL-ES.
Asunto(s)
Endosonografía/instrumentación , Vesícula Biliar/diagnóstico por imagen , Estómago/diagnóstico por imagen , Animales , Endoscopios , Diseño de Equipo , Humanos , PorcinosRESUMEN
We report the rare case of an intraductal papillary mucinous tumor (IPMT) in a man younger than 30 years of age. The patient was admitted with upper abdominal pain and an elevated amylase level of 662 IU/l. Ultrasonography showed a cystic mass in the pancreatic body and endoscopic retrograde cholangiopancreatography (ERCP) revealed a dilated pancreatic duct with a filling defect communicating with the tumor. He was successfully treated by segmental resection, which seems to be the best surgical option for pancreatic body tumors since it results in long-term survival and preserves as much pancreatic parenchyma as possible. Nevertheless, it can only be done in the absence of additional nodules along the pancreatic duct. A pathological diagnosis of intraductal papillary adenocarcinoma of the noninvasive type was confirmed, and both stumps were free of tumor.