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1.
Intern Med ; 62(2): 237-241, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35676043

RESUMEN

A 76-year-old woman with advanced pancreatic cancer developed recurrent cholecystitis after covered self-expandable metal stent (CSEMS) placement. The cholecystitis was refractory to repeated percutaneous transhepatic gallbladder drainage (PTGBD). Cholecystography showed a patent cystic duct with right and cranial side bifurcation, which is indicative of an increased likelihood of success of endoscopic transpapillary gallbladder drainage (ETGBD). We were able to manage the cholecystitis by ETGBD without further recurrence. ETGBD is considered an effective internal drainage method for the management of acute cholecystitis after CSEMS placement, and its indication may be decided on the basis of the findings of cholecystography through the PTGBD route.


Asunto(s)
Colecistitis Aguda , Colecistitis , Colestasis , Femenino , Humanos , Anciano , Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/cirugía , Stents , Colecistitis/complicaciones , Colecistitis/cirugía , Drenaje/métodos , Colecistitis Aguda/etiología , Colecistitis Aguda/cirugía , Colestasis/diagnóstico por imagen , Colestasis/etiología , Colestasis/cirugía
2.
Cancers (Basel) ; 14(24)2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36551574

RESUMEN

In this study, we aimed to evaluate the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) treatment for unresectable hepatocellular carcinoma (HCC) and to analyze the factors affecting overall survival (OS). A total of 69 patients who received Atez/Bev at our institutions for unresectable HCC were enrolled in this study. OS and progression-free survival (PFS) were estimated using the Kaplan−Meier method. Changes in clinical indicators within 3 months were defined as delta (∆) values, and the Cox proportional hazards model was used to identify which ∆ values affected OS. The median OS, PFS, objective response rate, and disease control rate were 12.5 months, 5.4 months, 23.8%, and 71.4%, respectively. During the observational period, 62 patients (92.5%) experienced AEs (hypertension (33.3%) and general fatigue), and 27 patients (47.4%) experienced grade ≥ 3 AEs (hypertension (10.1%) and anemia (7.2%)). There was a significant deterioration in the albumin-bilirubin (ALBI) score (−2.22 to −1.97; p < 0.001), and a reduction in PIVKA-II levels (32,458 to 11,584 mAU/mL; p = 0.040) within 3 months after commencing Atez/Bev. Both the worsening ∆ ALBI score (p = 0.005) and increasing ∆ PIVKA-II (p = 0.049) were significantly associated with the OS of patients.

3.
Clin J Gastroenterol ; 15(5): 946-952, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35913606

RESUMEN

We report a 61-year-old man treated with betamethasone for sudden-onset deafness. Several days later, he had a temperature > 38 °C. He sought care at another hospital and was admitted based on abnormal liver function tests (aspartate aminotransferase [AST], 866 IU/L [normal < 31 IU/L] and alanine aminotransferase [ALT] 1524 IU/L [normal < 31 IU/L]). Liver function improved daily and the patient was discharged from the hospital after 5 days. Two days after discharge, he had a recurrent fever and liver dysfunction. After admission to our hospital, liver function improved spontaneously. A liver biopsy was performed, but a diagnosis was not established; however, a tentative diagnosis of antinuclear antibody-negative autoimmune hepatitis was made and the patient was started on prednisolone (30 mg). Two days later, he developed a fever and persistent liver dysfunction, thus the prednisolone was discontinued. The next day, the AST and ALT increased significantly (18,000 and 12,000 U/L, respectively). Because the level of consciousness was altered, plasma exchange was started for acute liver failure. After discontinuing the prednisolone, the hospital course was uneventful. Drug-induced liver injury due to corticosteroids is rare. Herein, we report a patient with acute liver failure who survived with timely treatment.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatitis Autoinmune , Fallo Hepático Agudo , Corticoesteroides/uso terapéutico , Alanina Transaminasa , Anticuerpos Antinucleares , Aspartato Aminotransferasas , Betametasona , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hepatitis Autoinmune/etiología , Hepatitis Autoinmune/patología , Humanos , Hígado/patología , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/patología , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico
4.
J Gastroenterol ; 57(4): 322-332, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35233650

RESUMEN

BACKGROUND: Zinc deficiency is likely to occur in chronic liver disease. The aim of this study was to determine the prevalence of zinc deficiency in different types of chronic liver disease and to identify the factors that predicted low serum zinc levels. METHODS: The study was an observational single-center design. We obtained the medical records of 666 patients with chronic liver disease whose serum zinc levels had been measured. The cutoff value for zinc deficiency was a serum level < 70 µg/dL. RESULTS: Serum zinc levels in the alcoholic liver disease (ALD) group were significantly lower than in the other groups (hepatitis C virus [HCV], hepatitis B virus [HBV], and other cause) (P < 0.01). The CONUT and ALBI score (r = 0.527, P < 0.01), serum zinc level and ALBI score (r = - 0.607, P < 0.01), and serum zinc level and CONUT score (r = - 0.465, P < 0.01) correlated with each other. The prevalence of zinc deficiency were 44.8%, 63.2%, 86.7%, 97.1%, and 100% in the mALBI grade 1-CONUT normal, CONUT undernutrition, and mALBI grade 2a, 2b, and 3 groups, respectively. Multivariate analysis identified ALD, CONUT score, aspartate aminotransferase, and hemoglobin as significant, independent predictors of zinc deficiency (P < 0.05). CONCLUSIONS: This study identified ALD, CONUT score, aspartate aminotransferase, and hemoglobin as predictors of zinc deficiency in chronic liver disease. The rate of zinc deficiency is high even in patients classified as mALBI grade 1, especially in ALD, while caution may be required in those classified as mALBI grade 1-CONUT undernutrition.


Asunto(s)
Hepatopatías , Desnutrición , Aspartato Aminotransferasas , Humanos , Hepatopatías/epidemiología , Desnutrición/epidemiología , Estado Nutricional , Pronóstico , Estudios Retrospectivos , Zinc
5.
Intern Med ; 61(7): 951-958, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-34511564

RESUMEN

Objective The relationship between the prognosis and magnitude of a decrease in tumor blood flow according to estimated tumor differentiation remains unclear. This study investigated the relationship between reductions in the rate of mean computed tomography (CT) attenuation values and the clinical prognosis. Methods We evaluated 63 consecutive patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). The oncological aggressiveness of the tumors was estimated using classification by dynamic CT enhancement patterns. The utility of changes in mean CT attenuation values of intra-hepatic targets during treatment to estimate the prognosis was investigated by calculating the progression-free survival (PFS) and post-progression survival (PPS). A multivariate analysis was used to identify potential confounders for the survival after progression during lenvatinib therapy. Results The rate of decrease in the mean CT attenuation value gradually increased according to the degree of deterioration in estimated tumor differentiation, and the rate of a decrease in attenuation ≥40% showed a tendency to increase (p=0.064). This trend was reflected by a better objective response in oncological aggressiveness heterogeneous enhancement patterns (Type-3 and Type-4) than a homogeneous enhancement pattern (Type-2) (83% vs. 56% of modified Response Evaluation Criteria in Solid Tumors). This resulted in a similar PFS between the groups (p=0.773), whereas the PPS was significantly worse when the rate of decrease in the attenuation value was ≥40% (p=0.012). A multivariate analysis confirmed that a rate of decease in attenuation value ≥40% was a poor prognostic factor for the PPS (hazard ratio, 2.993; 95% confidence interval, 1.196-7.490; p=0.019). Conclusion A rate of decrease in attenuation ≥40% may reflect a good response of a highly malignant tumor to lenvatinib. Therefore, this value may have utility as a surrogate marker for estimating the oncological aggressiveness of tumors and their associated prognosis.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Quinolinas , Tomografía Computarizada por Rayos X/métodos
6.
Oncology ; 99(10): 611-621, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34139691

RESUMEN

BACKGROUND AND AIM: The aim of this study was to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of overall prognosis in patients with hepatocellular carcinoma treated with lenvatinib. METHODS: Forty-eight consecutive patients who received lenvatinib treatment were reviewed. The oncological aggressiveness of tumors estimated using 18F-FDG-PET/CT was investigated by the analysis of progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS). Multivariate analysis was used to identify potential confounders for OS during lenvatinib therapy. RESULTS: Using the Modified Response Evaluation Criteria in Solid Tumors, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with a better objective response to lenvatinib than a TLR <2 (78 vs. 62%), resulting in a similar PFS (p = 0.751). Because of a significantly worse PPS, OS with a TLR ≥2 was poor compared to a TLR < 2 (p = 0.012). Multivariate analysis confirmed that a TLR ≥ 2 was associated with poor OS (hazard ratio, 2.709; 95% CI, 1.140-6.436; p = 0.024). Analysis of 24 patients who received a repeat 18F-FDG-PET/CT showed that daily changes expressed as ΔTLR × 103/day over the treatment course tended to be different among the types of subsequent treatment. A R0 resection and lenvatinib-TACE sequential therapy provided good disease control (median, -4.593 and -0.024, respectively) compared with other treatments (median, 5.278) (p = 0.075). CONCLUSION: Lenvatinib has acceptable disease control regardless of estimated tumor differentiation. A high TLR (≥2) is a poor prognostic factor of OS following lenvatinib treatment, while ΔTLR × 103/day provides useful information of disease control status.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Quinolinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Radiofármacos , Tasa de Supervivencia , Resultado del Tratamiento
7.
Clin J Gastroenterol ; 14(2): 555-559, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33428067

RESUMEN

We report a rare case of amebiasis associated with an intraabdominal abscess without colitis, an intestinal perforation, or other extraintestinal amebiasis. A patient was admitted with cirrhosis and a history of spontaneous bacterial peritonitis (SBP) and was found to have a high C-reactive protein (CRP) level. Dynamic CT and ultrasound echo findings showed an intraabdominal abscess. No intestinal lesions or extraintestinal lesions other than the intraabdominal abscess were observed. Blood cultures and puncture fluid cultures were negative for bacteria. However, microscopic examination of the puncture fluid showed a cystic form of amoeba, leading to a diagnosis of an amoeba abscess. The abscess disappeared after 10 days of oral treatment with metronidazole. When an abdominal abscess is seen in an immunocompromised patient such as a cirrhotic patient, amoeba infection should be considered as a possible diagnosis.


Asunto(s)
Absceso Abdominal , Amoeba , Entamoeba histolytica , Entamebiasis , Absceso Hepático Amebiano , Absceso Abdominal/diagnóstico por imagen , Absceso Abdominal/tratamiento farmacológico , Absceso Abdominal/etiología , Humanos , Absceso Hepático Amebiano/complicaciones , Absceso Hepático Amebiano/diagnóstico , Absceso Hepático Amebiano/tratamiento farmacológico , Metronidazol/uso terapéutico
8.
Hepatol Res ; 51(1): 62-68, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32939922

RESUMEN

AIM: The number of patients with fatty liver disease (FLD) is increasing globally. Ethanol consumption in FLD is known to be associated with an increased risk of hepatocellular carcinoma (HCC), but the effects of alcohol consumption on the occurrence of multiple HCCs remain unclear. We explored the relationship between the daily ethanol intake and the HCC number. METHODS: This single-center retrospective study enrolled 114 patients without viral or immune hepatitis undergoing first-line HCC treatment who had been diagnosed with FLD by abdominal ultrasonography or a liver biopsy at the same time as or before HCC detection. We categorized patients into four groups according to the daily alcohol consumption (<20 g: non-alcoholic fatty liver disease, n = 45; 20-39 g: low-intermediate ethanol intake with FLD, n = 13; 40-69 g: high-intermediate ethanol intake with FLD, n = 31; ≥70 g: alcoholic fatty liver disease, n = 25). The relationship between the daily ethanol consumption and the number of HCCs (single or multiple) was examined. RESULTS: The risk of multiple HCCs was significantly higher in the high-intermediate ethanol intake with FLD (HR 2.89, 95% CI 1.04-8.02, P = 0.042) and alcoholic fatty liver disease (HR 3.14, 95% CI 1.07-9.22, P = 0.037) groups than in the others. A multivariate analysis showed that a daily ethanol intake ≥40 g was associated with a significantly increased risk of multiple HCCs (HR 2.82, 95% CI 1.16-6.88, P = 0.023). CONCLUSIONS: Our findings suggest that a high daily ethanol intake might lead to multiple hepatocarcinogenesis in patients with FLD.

9.
Intern Med ; 60(3): 345-351, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32963154

RESUMEN

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea , Quinolinas , Estudios Retrospectivos , Ramucirumab
10.
Oncology ; 99(3): 169-176, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33207358

RESUMEN

BACKGROUND: The sensitivity of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in hepatocellular carcinoma (HCC) is low; however, clinical evidence demonstrating its prognostic value in patients with HCC has recently been reported. This study aimed to assess the value of 18F-FDG-PET/CT as a tool for evaluating the response of HCC to lenvatinib treatment. METHODS: We evaluated 11 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 18F-FDG-PET/CT from April 2018 to December 2019. The tumor-to-normal liver ratio (TLR) of the target tumor was measured before and during the course of lenvatinib treatment with 18F-FDG-PET/CT (pre and post analysis, respectively), with a TLR ≥2 classified as PET-positive HCC. At the time of each evaluation, we also used the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the modified RECIST (mRECIST), and the tumor marker alfa-fetoprotein (AFP). RESULTS: Of 11 patients, 3 (27%) and 8 (73%) had an objective response to lenvatinib treatment at the time of post-analysis by RECIST 1.1 and mRECIST, respectively. There were 3 (27%) and 7 (64%) patients with PET-positive HCC at the time of pre- and post-analysis, respectively. There was a significant correlation between the rates of change in AFP and TLR during lenvatinib treatment (r = 0.69, p = 0.019). Based on these results, we were able to perform liver resection on 4 patients with PET-positive HCC as conversion therapy. Three samples from these patients showed poorly differentiated tumors. CONCLUSION: 18F-FDG-PET/CT has potential as an evaluation tool for describing biological tumor behavior and reflecting disease progression, location, and treatment response. This modality may provide useful information for considering prognosis and subsequent therapy.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Quinolinas/administración & dosificación , Administración Oral , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/cirugía , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , alfa-Fetoproteínas/análisis
11.
BMC Gastroenterol ; 20(1): 368, 2020 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-33148171

RESUMEN

BACKGROUND: The prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index < 25.0 kg/m2) are unknown. METHODS: In this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3-4) and mortality in lean NAFLD patients. RESULTS: Glycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan-Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ - 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ - 1.455 were predictors of overall survival. CONCLUSIONS: Although patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ - 1.455 or history of liver cancer should be monitored carefully during follow-up.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hígado , Enfermedad del Hígado Graso no Alcohólico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Pronóstico , Estudios Retrospectivos , Adulto Joven
12.
Intern Med ; 59(20): 2511-2516, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32581173

RESUMEN

We report a 71-year-old man with non-B non-C chronic liver damage who had been regularly visiting our hospital since he was 38 years of age. He underwent three partial hepatectomies for hepatocellular carcinoma (HCC) diagnosed at 65, 67, and 71 years of age, respectively. A histopathological examination showed moderately-differentiated HCC, and chronic hepatitis with mild fibrosis stage in non-tumor areas. alpha-fetoprotein (AFP) and PIVKAII were not useful for the early prediction of HCC, but TERT promotor mutation (C228T) in serum cell-free DNA was useful. This is the first report on the importance of long-term follow-up in non-B non-C chronic liver damage, regardless of the fibrosis stage.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Pruebas de Función Hepática/estadística & datos numéricos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/fisiopatología , Estudios de Seguimiento , Hepatectomía , Humanos , Neoplasias Hepáticas/fisiopatología , Masculino , Persona de Mediana Edad , Mutación , Estudios de Tiempo y Movimiento , alfa-Fetoproteínas/genética
13.
Liver Cancer ; 9(6): 756-770, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33442544

RESUMEN

BACKGROUND: The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). METHODS: Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. RESULTS: Heterogeneous enhancement patterns (Type-3 and -4), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (Type-2) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (p = 0.313). Because of significantly worse PPS, overall survival of Type-4 tumor was poor compared to Type-2 or -3 tumors (p = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01-0.71; p = 0.023), while Type-4 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06-8.05; p = 0.039). CONCLUSION: Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.

14.
Int J Mol Sci ; 18(2)2017 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-28212276

RESUMEN

Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model.


Asunto(s)
Anticarcinógenos/farmacología , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias del Colon/patología , Pentoxifilina/farmacología , Lesiones Precancerosas , Animales , Biomarcadores , Proliferación Celular/efectos de los fármacos , Quimioprevención , Neoplasias del Colon/etiología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/prevención & control , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental , Modelos Animales de Enfermedad , Expresión Génica , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/complicaciones , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , beta Catenina/metabolismo
15.
J Gastroenterol ; 50(3): 323-32, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24817668

RESUMEN

BACKGROUND: Skeletal muscle depletion or sarcopenia has been identified as a poor prognostic factor for various diseases. The aim of this study is to determine whether muscle depletion is a prognostic factor for hepatocellular carcinoma (HCC). METHODS: We evaluated 217 consecutive patients with primary HCC. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the total body fat-free mass (FFM) and L3 skeletal muscle index (L3 SMI) were obtained. The factors contributing to overall survival (OS) were analyzed by univariate and multivariate Cox proportional hazards model. RESULTS: In univariate analysis, FFM (P = 0.0422), Child-Pugh classification (P = 0.0058), serum albumin level (P < 0.0001), serum AFP level (P < 0.0001), serum proteins induced by vitamin K absence or antagonist-II level (P < 0.0001), cancer stage (P < 0.0001), and curability of the initial treatment (P < 0.0001) were significantly associated with the prognosis of HCC. Multivariate analysis indicated that FFM (P = 0.0499), albumin level (P = 0.0398), and curability of the initial treatment (P = 0.0008) were independent prognostic factors. Sarcopenia was defined as an L3 SMI value of ≤29.0 cm(2)/m(2) for women and ≤36.0 cm(2)/m(2) for men, and 24 patients (11.1%) have sarcopenia. Sarcopenic patients showed a significantly lower OS than those without sarcopenia (P = 0.0043). Sarcopenic patients who were overweight (BMI >22) died earlier (P = 0.0129). CONCLUSIONS: Skeletal muscle depletion is an independent prognostic factor. Intervention to prevent muscle wasting might be an effective strategy for improving the outcome of HCC.


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Neoplasias Hepáticas/complicaciones , Sarcopenia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Índice de Masa Corporal , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Estadificación de Neoplasias , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/diagnóstico por imagen , Sarcopenia/patología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
16.
Hepatol Res ; 43(5): 467-74, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23072582

RESUMEN

AIM: Radiofrequency ablation (RFA) is a promising alternative to hepatic resection for the treatment of hepatocellular carcinoma (HCC) located in the caudate lobe. We evaluated the therapeutic efficacy and safety of RFA for HCC located in the caudate lobe compared with HCC located elsewhere in the liver. METHODS: Overall, 555 consecutive patients treated by RFA for a single HCC tumor of less than 3 cm diameter, were enrolled in this study, including 20 patients with HCC located in the caudate lobe. Among these 20 patients, HCC was located in the Spiegel lobe in eight patients, in the paracaval portion in another 10 and in the caudate process in two. We evaluated differences in the local recurrence rate and the incidence of complications associated with RFA between the caudate and the non-caudate groups. RESULTS: The 4-year cumulative local recurrence rate after RFA in the caudate group and the non-caudate group was 22.3% and 4.5%, respectively (P < 0.001). Multivariate analysis of factors affecting local recurrence demonstrated that tumor size and tumor location (caudate or non-caudate) were independent significant factors. No postoperative complications were observed in the caudate group, whereas 15 patients (2.8%) in the non-caudate group experienced complications related to RFA. CONCLUSION: We were able to safely treat HCC located in the caudate lobe by RFA. However, there was a high incidence of local recurrence, presumably because of the heat sink effect of the inferior vena cava and the restricted puncture approach. We should pursue a revised method to reduce local recurrence.

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