Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study.

AIM: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older. METHODS: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed. RESULTS: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group. CONCLUSIONS: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients.

Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. METHODS: A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. RESULTS: Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 104/µL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0). CONCLUSION: The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.

Comparing the Efficacy and Safety of Gemcitabine plus Nab-Paclitaxel versus Gemcitabine Alone in Older Adults with Unresectable Pancreatic Cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC. PATIENTS AND METHODS: In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses. RESULTS: GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant. CONCLUSION: GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.

Endoscopic ultrasound-guided fine needle aspiration for diagnosing pancreatic mass in patients with surgically altered upper gastrointestinal anatomy.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established as a safe and accurate method for diagnosing a pancreatic mass; however, EUS-FNA for patients with surgically altered upper gastrointestinal (UGI) anatomy has not yet been investigated sufficiently. Therefore, the feasibility and safety of EUS-FNA in these patients were retrospectively investigated. METHODS: Patients in whom EUS-FNA was performed between March 2008 and April 2017 were retrospectively investigated in terms of EUS-FNA technical success, procedure time, diagnostic accuracies of cytology and histology, and procedure-related adverse events. RESULTS: Twenty-five EUS-FNAs were performed for 15 pancreatic body-to-tail and 10 head lesions. All patients underwent EUS-FNA successfully; however, changing of the echoendoscope to a forward-viewing echoendoscope and preplacement of a nasobiliary catheter by balloon-assisted enteroscopy for guidance were needed in one and two cases, respectively. The median procedure time was 26 min (range, 16-70). The diagnostic accuracies were 76%, 84%, and 88% for cytology, histology, and combined use, respectively. Adverse events were not observed. CONCLUSIONS: Endoscopic ultrasound-guided FNA is a safe and efficient method for diagnosing a pancreatic mass even in patients with surgically altered UGI anatomy. Nevertheless, some sophisticated techniques are required for pancreatic head lesions if reaching the duodenum after passing through the jejunal limb is required for visualization of the pancreatic mass.

Rare sugars, d-allulose, d-tagatose and d-sorbose, differently modulate lipid metabolism in rats.

BACKGROUND: Rare sugars including d-allulose, d-tagatose, and d-sorbose are present in limited quantities in nature; some of these rare sugars are now commercially produced using microbial enzymes. Apart from the anti-obesity and anti-hyperglycaemic activities of d-allulose, effects of these sugars on lipid metabolism have not been investigated. Therefore, we aimed to determine if and how d-tagatose and d-sorbose modulate lipid metabolism in rats. After feeding these rare sugars to rats, parameters on lipid metabolism were determined. RESULTS: No diet-related effects were observed on body weight and food intake. Hepatic lipogenic enzyme activity was lowered by d-allulose and d-sorbose but increased by d-tagatose. Faecal fatty acid excretion was non-significantly decreased by d-allulose, but significantly increased by d-sorbose without affecting faecal steroid excretion. A trend toward reduced adipose tissue weight was observed in groups fed rare sugars. Serum adiponectin levels were decreased by d-sorbose relative to the control. Gene expression of cholesterol metabolism-related liver proteins tended to be down-regulated by d-allulose and d-sorbose but not by d-tagatose. In the small intestine, SR-B1 mRNA expression was suppressed by d-sorbose. CONCLUSION: Lipid metabolism in rats varies with rare sugars. Application of rare sugars to functional foods for healthy body weight maintenance requires further studies. © 2017 Society of Chemical Industry.

A case of extrahepatic growth-type hepatocellular carcinoma presenting with bleeding from colonic metastasis.

A 60-year-old woman visited our hospital due to hematochezia. Colonoscopy revealed a 50-mm-diameter submucosal tumor with ulceration of the left side of the transverse colon, and magnetic resonance imaging (MRI) demonstrated the presence of small hepatic nodules. Submucosal tumor of the colon with liver metastasis was therefore diagnosed. To prevent tumor bleeding, we performed partial transverse colectomy. The histopathological diagnosis was moderately differentiated hepatocellular carcinoma presenting as a submucosal tumor with a high frequency of vascular invasion. Computed tomography (CT) angiography revealed a 40-mm-diameter confluent multinodular-type hepatocellular carcinoma with outward spread from segment II and multiple intrahepatic metastases. Our final diagnosis was hepatocellular carcinoma with hematogenous colon metastasis.

Clinical characteristics and prognosis of non-B non-C hepatocellular carcinoma patients with modest alcohol consumption.

AIM: Alcoholic hepatocellular carcinoma (ALD-HCC) accounts for the majority of non-B non-C HCC (NBNC-HCC) cases. Although alcohol is a potent carcinogen, there have been few reports on the influence of modest alcohol consumption in NBNC-HCC. This study aimed to investigate the clinical characteristics and prognosis of NBNC-HCC patients with modest alcohol consumption. METHODS: From 2007 to 2010, 2283 HCC patients were evaluated at 10 hospitals. We collected detailed etiology data of 588 NBNC-HCC patients and compared the clinical characteristics and prognosis between ALD-HCC and modest alcohol-HCC patients. RESULTS: There were 69 HCC patients with modest alcohol consumption, accounting for 3% of all HCC patients evaluated. This patient group had significantly more women and higher prevalence of Child-Pugh class A, hypertension and advanced disease stage, and were diagnosed with HCC at an older age than the ALD-HCC group (266 patients). Additionally, among the modest alcohol-HCC patients, diabetes was significantly more common in the anti-hepatitis B core (HBc) negative subgroup than in the anti-HBc positive subgroup. However, no significant difference in survival was observed between the two patient groups regardless of significant differences in tumor staging. Alcohol consumption and metabolic factors were not significant independent predictors of survival. CONCLUSION: The clinical characteristics of modest alcohol-HCC included advanced staging, favorable liver reserve capacity and older age at diagnosis. HCC development in patients with modest alcohol consumption may relate to metabolic factors. Although approximately 30% of the evaluated HCC cases were in advanced stages, the prognosis of NBNC-HCC patients with modest alcohol consumption was relatively favorable.

NMR spectroscopic and quantum mechanical analyses of enhanced solubilization of hesperidin by theasinensin a.

PURPOSE: The use of hesperidin in the pharmaceutical field is limited by its aqueous insolubility. The effects of natural compounds in tea on the solubility of hesperidin were evaluated and the underlying mechanism was investigated by nuclear-magnetic resonance (NMR) and quantum mechanical calculations. METHODS: The solubility of hesperidin was measured by liquid chromatography time-of-flight mass spectrometry; the structure of the hesperidin/theasinensin A complex was characterized by (1)H-NMR, diffusion-ordered NMR spectroscopy, and rotating frame NOE spectroscopy, as well as theoretically by quantum mechanical calculations. RESULTS: Among the natural compounds in tea, theasinensin A was the most effective in improving hesperidin solubility. The complexation of hesperidin with theasinensin A led to changes in the chemical shift of protons in hesperidin (Δδ: 0.01-0.27 ppm) and diffusion coefficient (ΔD: 0.66-1.32 × 10(-10) m(2)/s) of hesperidin. ROE correlation signals between hesperidin and theasinensin A and quantum mechanical calculations revealed that two hesperidin molecules formed a stable complex with theasinensin A (2:1 complex) with a ΔG energy of -23.5 kJ/mol. CONCLUSIONS: This is the first study that provides insight into the enhanced solubility of hesperidin through interactions with theasinensin A via a 2:1 complex formation between hesperidin and theasinensin A.

High-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats.

AIM: The development of fibrosis is considered an important phase in the progress of non-alcoholic steatohepatitis (NASH) towards the end stage of liver disease, including cirrhosis. However, few small animal models can display NASH-associated fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis using genetically normal rats. METHODS: Nine-week-old male Sprague-Dawley rats were fed with normal, high-fat (HF), or two types of high-fat and high-cholesterol (HFC) diets for 9 weeks (n = 5 each). All HFC diets contained 1.25% or 2.5% cholesterol. RESULTS: The rats fed with the HF diet developed mild steatosis and inflammation without fibrosis at 18 weeks of age, whereas all rats given the HFC diet developed obvious steatosis and inflammation with hepatocyte ballooning and fibrosis. Two of five (40%) rats given the HFC diet containing 2.5% cholesterol progressed to liver cirrhosis. Hepatic total cholesterol levels were significantly higher in rats given the HFC, than the normal or HF diets. The HFC diet significantly and dose-dependently decreased microsomal triglyceride transfer protein expression. Cholesterol tended to suppress carnitine palmitoyltransferase activity and adenosine triphosphate-binding cassette transporter G5 expression. Adding cholesterol to the HF diet modified hepatic lipid metabolism at the molecular level. CONCLUSION: The HFC diet induced hepatic features of NASH and eventually progressed cirrhosis in Sprague-Dawley rats within 9 weeks.

[Rehabilitative Intervention for Low Back Pain].

In the evolution process to a bipedalism animal, human's spinal structure has been formed by responding to the contradicting functions (firm and flexibility). Thus, low back pain easily occurs even by a break of extremely slight balance. As for the cause of the pain, a consistency theory is not established, and we need to depend on conservative treatment for the treatment And the leading role of the conservative therapy is rehabilitation. In this report, we introduce scientific evidence for the effect of the rehabilitative intervention for low back pain.

Hypolipidemic potential of squid homogenate irrespective of a relatively high content of cholesterol.

BACKGROUND: Our previous study has shown that regardless of a relatively high amount of cholesterol, squid homogenate lowers serum and hepatic cholesterol in animals. Since this work, we have developed a new method to inhibit autolysis of squid proteins with sodium citrate. This study aims to investigate how squid homogenate prepared with sodium citrate affects lipid metabolism in Sprague-Dawley rats at the molecular level. METHODS: We prepared squid homogenate with sodium citrate to inhibit autolysis of squid protein. In Experiment 1 (Exp. 1), rats were given a cholesterol-free control diet or a squid diet, with squid homogenate added at the level of 5% as dietary protein for 4 weeks. Blood, the liver and adipose tissue were taken after 6 hours fasting. Serum and hepatic lipids and activities of enzymes related to lipid metabolism were measured. In Experiment 2 (Exp. 2), the above-mentioned diets had cholesterol added at the level of 0.1% and given to rats. Lipid parameters, enzyme activities, and gene expression of proteins involved in lipid metabolism in the liver and the small intestine were determined. In addition, feces were collected for two days at the end of Exp. 2 to measure fecal excretion of steroids. RESULTS: In Exp.1, serum triglyceride and cholesterol were ~50% and ~20% lower, respectively, in the squid diet-fed rats than in the control diet-fed animals while hepatic cholesterol was ~290% higher in the squid diet-fed rats. When cholesterol was included into the diets (Exp. 2), serum lipids were significantly lower in the squid group while no difference of hepatic lipid was seen between two groups. Activities of hepatic lipogenic enzymes were significantly lower in rats on the squid diet while the enzyme responsible for fatty acid oxidation was not modified (Expt. 1 and 2). Hepatic level of mRNA of microsomal triglyceride transfer protein was significantly lower in the squid group. In the small intestine, the squid diet exhibited significantly lower gene expression of proteins involved in fatty acid transport and cholesterol absorption. Fecal secretion of acidic steroids, but not neutral steroids, was higher in rats fed the squid diet than in those fed the control diet. CONCLUSION: These results imply that newly-developed squid homogenate has hypolipidemic potential primarily through decreased absorption of bile acids in the small intestine and suppressed lipogenesis in the liver.

Oral Administration of Chaetoceros gracilis-A Marine Microalga-Alleviates Hepatic Lipid Accumulation in Rats Fed a High-Sucrose and Cholesterol-Containing Diet.

Microalgae are attracting attention as a next-generation alternative source of protein and essential fatty acids that do not consume large amounts of water or land. Chaetoceros gracilis (C. gracilis)-a marine microalga-is rich in proteins, fucoxanthin, and eicosapentaenoic acid (EPA). Growing evidence indicates that dietary fucoxanthin and EPA have beneficial effects in humans. However, none of these studies have shown that dietary C. gracilis has beneficial effects in mammals. In this study, we investigated the effects of dietary C. gracilis on lipid abnormalities in Sprague-Dawley rats fed a high-sucrose cholesterol-containing diet. Dried C. gracilis was added to the control diet at a final dose of 2 or 5% (w/w). After four weeks, the soleus muscle weights were found to be dose-responsive to C. gracilis and showed a tendency to increase. The hepatic triglyceride and total cholesterol levels were significantly reduced by C. gracilis feeding compared to those in the control group. The activities of FAS and G6PDH, which are related to fatty acid de novo synthesis, were found to be dose-responsive to C. gracilis and tended to decrease. The hepatic glycerol content was also significantly decreased by C. gracilis feeding, and the serum HDL cholesterol levels were significantly increased, whereas the serum levels of cholesterol absorption markers (i.e., campesterol and ß-sitosterol) and the hepatic mRNA levels of Scarb1 were significantly decreased. Water-soluble metabolite analysis showed that the muscular contents of several amino acids, including leucine, were significantly increased by C. gracilis feeding. The tendency toward an increase in the weight of the soleus muscle as a result of C. gracilis feeding may be due to the enhancement of muscle protein synthesis centered on leucine. Collectively, these results show that the oral administration of C. gracilis alleviates hepatic lipid accumulation in rats fed a high-sucrose and cholesterol-containing diet, indicating the potential use of C. gracilis as a food resource.

Re-intervention with 10-mm vs 12-mm covered self-expandable metallic stent for recurrent unresectable distal biliary obstruction in patients with previous stent implantation.

BACKGROUND: Treatment for unresectable distal malignant biliary obstruction (DMBO) involves placing a 10-mm covered self-expandable metallic stent (CSEMS). In recurrent biliary obstruction (RBO), replacement of the CSEMS is recommended; however, the appropriate stent type remains unknown. We speculated that large-bore CSEMSs would provide longer patency. We compared the efficacy of 10-mm and 12-mm CSEMS in patients with RBO. METHODS: We retrospectively retrieved data on patients who underwent CSEMS replacement from the endoscopic database. We investigated the time to RBO (TRBO) after CSEMS replacement. The hazard ratio (HR) for the the second TRBO was estimated using the Cox proportional hazard model. The estimated median second TRBO was determined using the Kaplan-Meier method. RESULTS: Among the 493 patients with DMBOs treated with 10-mm CSEMS, 48 and 29 patients underwent re-intervention with 10-mm and 12-mm CSEMS, respectively. The use of 12-mm CSEMS was inversely associated with second TRBO (multivariable-adjusted HR, 0.62; 95% CI, 0.39-0.98; P = .042). The estimated median second TRBO was greater with the 12 mm CSEMS than with the 10 mm variety (562 days vs 207 days; P = .019). CONCLUSION: The second intervention with 12-mm CSEMS was associated with a longer TRBO.

Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

AIM: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. MATERIALS/METHODS: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. RESULTS: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. CONCLUSIONS: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach.

AIM: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. METHODS: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. RESULTS: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev. CONCLUSIONS: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN.

Potential of PALBI-T score as a prognostic model for hepatocellular carcinoma in alcoholic liver disease.

BACKGROUND AND AIM: With the control of viral hepatitis, alcoholic hepatocellular carcinoma (HCC) is becoming increasingly important in Japan. In alcoholic cirrhosis, the impact of portal hypertension is significant. Thus, it may be difficult to predict prognosis accurately with the reported prognostic scores. Here we propose the platelet-albumin-bilirubin tumor nodes metastasis (TNM) score (PALBI-T score) as a prognostic model for HCC in alcoholic liver disease, and investigate its usefulness. The PALBI-T score is an integrated score based on the TNM stage and PALBI grade including platelets, reflecting portal hypertension. METHODS: This study included 163 patients with alcoholic HCC treated at our Center from 1997 to 2018. We compared the prognostic prediction abilities of the Japan Integrated Staging (JIS) score, ALBI-T score, and PALBI-T score. The PALBI-T score was calculated similarly to the JIS and ALBI-T scores. Areas under the receiver operating characteristic curve (AUC) were calculated for predicting overall survival (OS). RESULTS: In predicting the 1-year survival, the JIS score had a larger AUC (AUC = 0.925) than the ALBI-T score (AUC = 0.895) and PALBI-T score (AUC = 0.891). On the other hand, there was no significant difference in predicting OS among the integrated scores. The PALBI-T score (AUC = 0.740) had the largest AUC, and the JIS score (AUC = 0.729) and ALBI-T score (AUC = 0.717) were not significantly different from the PALBI grade (AUC = 0.634). The PALBI grade reflected the degree of portal hypertension. CONCLUSION: In patients with alcoholic HCC, the Japan Integrated Staging score is useful for predicting short-term prognosis. The PALBI-T score, which reflects portal hypertension, appears to be a more valid prognostic score for predicting long-term prognosis.

Environmental factors, medical and family history, and comorbidities associated with primary biliary cholangitis in Japan: a multicenter case-control study.

BACKGROUND: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case-control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case-control study to identify the environmental factors associated with the development of PBC in Japan. METHODS: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. RESULTS: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01-2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07-1.92), ever smoking (OR, 1.70; 95% CI, 1.28-2.25), and hair dye use (OR, 1.57; 95% CI, 1.15-2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99-19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077-0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52-68.0) in the model for medical and familial factors. CONCLUSIONS: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

Role of endoscopic ultrasound for gallbladder disease.

Endoscopic ultrasonography (EUS) has excellent spatial resolution and allows more detailed examination than abdominal ultrasonography (US) in terms of qualitative diagnosis of tumors and evaluation of tumor invasion depth. To understand the role of EUS in gallbladder disease, we need to understand the normal gallbladder wall structure and how to visualize it on EUS. In addition, gallbladder lesions can be classified into two broad categories: protuberant and wall-thickening lesions. Here, the features on EUS were outlined. We also outlined the current status of EUS-FNA for gallbladder lesions as there have been scattered reports of EUS-FNA in recent years.

Hypotriacylglycerolemic and antiobesity properties of a new fermented tea product obtained by tea-rolling processing of third-crop green tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves.

We manufactured a new fermented tea by tea-rolling processing of third-crop green tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves. The mixed fermented tea extract inhibited pancreatic lipase activity in vitro, and effectively suppressed postprandial hypertriacylglycerolemia in rats. Rats fed a diet containing 1% freeze-dried fermented tea extract for 4 weeks had a significantly lower liver triacylglycerol concentration and white adipose tissue weight than those fed the control diet lacking fermented tea extract. The activity of fatty acid synthase in hepatic cytosol markedly decreased in the fermented tea extract group as compared to the control group. The serum and liver triacylglycerol- and body fat-lowering effects of the mixed fermented tea extract were strong relative to the level of dietary supplementation. These results suggest that the new fermented tea product exhibited hypotriacylglycerolemic and antiobesity properties through suppression of both liver fatty acid synthesis and postprandial hypertriacylglycerolemia by inhibition of pancreatic lipase.