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The development of modern endoscopic techniques, easier and greater access to healthcare, and interest in Helicobacter pylori infection and its implications have all led to a significant increase in upper endoscopies. In turn, gastroenterologists and pathologists have been recognizing an ever-increasing number of patterns of mucosal injury. Consequently, there is now an interest in a wider aspect of non-neoplastic gastric pathology, namely, non-HP (H. pylori) gastritis. In this review, we present major clinico-pathological entities, based on either the salient morphological features or the underlying etiologies. [ABSTRACT FROM AUTHOR]

The association of primary biliary cirrhosis (PBC) and bronchial asthma was observed in three patients. All of these patients were female (53, 54, and 41 years old, respectively), and were positive for antimitochondrial antibodies. The patients fulfilled the diagnostic criteria of both PBC and bronchial asthma. Bronchial asthma preceded PBC in two patients, and the reverse order was seen in the other. Patient the clinical symptoms were mainly due to the bronchial asthma. Two patients had asymptomatic PBC and the third patient complained of pruritus. The liver histology showed mild to moderate eosinophilic infiltration in addition to the ductal and hepatic parenchymal changes characteristic of PBC. A survey of 266 cases of PBC referred to us disclosed that, in 6 of these, the PBC was associated with bronchial asthma, while no association with bronchial asthma was the material of found in 166 patients with viral hepatitis in our liver biopsy files. The 3 present cases we experienced suggest that bronchial asthma may be included in the list of extrahepatic diseases associated with PBC. The significance of this association is unclear and may merit further study. Steroid therapy, which is known to cause adverse effects in PBC, was employed for bronchial asthma in these 3 patients. Another therapeutic approach will have to be considered in patients with bronchial asthma associated with PBC. [ABSTRACT FROM AUTHOR]

The determination of the volume, amylase content and bicarbonate concentration in pancreatic juice after Pancreozymin-Secretin stimulation had been considered to be valuable for the diagnosis of pancreatic diseases. However, since these values were not always coincidental, the diagnosis of pancreatic diseases were difficult in many cases. To have a more difinite criteria of Pancreozymin-Secretin test, the content of carboxypeptidase A and B in the juice was compared with other results and the secretory mechanism of this enzyme were investigated by the method of radioactive zinc. As the results, it has been provided that the determination of carboxypeptidase A and B was also as useful as the measurement of the volume, amylase out put and maximum concentration of bicarbonate for more distinct diagnosis qualitatively and quantitatively of pancreatic disease on Pancreozymin-Secretin test. The maximal radioactivity was obtained in the pancreatic juice between 3 to 6 hours after intravenous injection of Zn in normal rats. The radioactivity and the carboxypeptidase activity in the juice was completely paralleled by sephadex and cellulose column Chromatographie analysis. Thus, it was assuemed that Zn was excreted as a component of that enzyme protein moiety and time needed for synthesis and excretion of that enzyme might be between 3 to 6 hours. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a serious complication of cirrhosis. This study analyzed the prognostic effect of AKI in patients with cirrhosis and its risk factors, particularly in relation to amino acid imbalance., Methods: This retrospective study reviewed 808 inpatients with cirrhosis at two institutes in Gifu, Japan. AKI was diagnosed according to the recommendations of the International Club of Ascites. Amino acid imbalance was assessed by measuring serum branched-chain amino acid (BCAA) levels, tyrosine levels, and the BCAA-to-tyrosine ratio (BTR). Factors associated with mortality and AKI development were assessed using the Cox proportional hazards regression model with AKI as a time-dependent covariate and the Fine-Gray competing risk regression model, respectively., Results: Of the 567 eligible patients without AKI at baseline, 27% developed AKI and 25% died during a median follow-up period of 4.7 years. Using a time-dependent covariate, AKI development (hazard ratio [HR], 6.25; 95% confidence interval [CI], 3.98-9.80; p < 0.001) was associated with mortality in patients with cirrhosis independent of potential covariates. In addition, alcohol-associated/-related liver disease, metabolic dysfunction-associated steatohepatitis, Child-Pugh score, and BTR (subdistribution HR 0.78; 95% CI 0.63-0.96; p = 0.022) were independently associated with AKI development in patients with cirrhosis. Similar results were obtained in the multivariate model that included BCAA and tyrosine levels instead of BTR., Conclusions: AKI is common and associated with mortality in Japanese patients with cirrhosis. An amino acid imbalance is strongly associated with the development of AKI in patients with cirrhosis., (© 2024. The Author(s).)

Background: Rapid skeletal muscle loss adversely affects the clinical outcomes of liver cirrhosis. However, the relationships between the annual changes in skeletal muscle area (ΔSMA/year) and the etiology of cirrhosis, factors associated with muscle loss, and risk of mortality remains unclear., Methods: A total of 384 patients who underwent multiple computed tomography (CT) scans between March 2004 and June 2021 were enrolled in this study (median age, 67 years; 64% men; median model for end-stage liver disease score, 9). Body composition and ΔSMA/year were estimated using a 3D image analysis system and data from at least two distinct CT scans. Differences in ΔSMA/year among different etiologies of cirrhosis, factors associated with rapid muscle loss (defined as ΔSMA/year ≤  - 3.1%), and the association between ΔSMA/year and mortality were examined., Results: Patients with alcohol-associated liver disease (ALD) cirrhosis experienced more rapid muscle loss (ΔSMA/year, - 5.7%) than those with hepatitis B (ΔSMA/year, - 2.8%) and hepatitis C cirrhosis (ΔSMA/year, - 3.1%). ALD cirrhosis was independently associated with ΔSMA/year ≤  - 3.1% after adjusting for age, sex, and liver functional reserve. Over a median follow-up period of 3.8 years, ALD cirrhosis, ΔSMA/year ≤  - 3.1%, and low subcutaneous adipose tissue level were found to be significantly associated with reduced survival. ALD cirrhosis (hazard ratio [HR], 2.43; 95% confidence interval [CI] 1.12-5.28) and ΔSMA/year ≤  - 3.1% (HR, 3.68; 95% CI 2.46-5.52) were also predictive of mortality., Conclusions: These results suggest that ALD cirrhosis increases the risk of rapid muscle loss and mortality in affected patients., (© 2024. The Author(s).)

Background: Physical activity can reduce the risk of morbidity and mortality in patients with chronic liver disease (CLD), whereas physical inactivity adversely affects clinical outcomes. Since data on physical activity in CLD are scarce, we conducted a questionnaire survey to assess the physical activity patterns and determinants in patients with CLD., Methods: We surveyed 437 patients from outpatient clinics at Gifu University Hospital about their physical activity patterns and determinants in 2022 using a validated questionnaire. The primary objective was to examine the proportion of patients who exercised and the clinical characteristics of patients who achieved high levels of physical activity. The secondary objectives were to explore the types, motivations, barriers, and preferences for physical activity., Results: Among the 397 eligible patients (median age 68 years; 51% men; and median Model for End-Stage Liver Disease score 6), 55.4% reported performing physical activity less than once a week. Physical activity frequency was not associated with sex, body mass index, comorbidities, or hepatic reserve. Among the respondents, 60.4% expressed concern regarding physical strength, and 80.6% expressed concern regarding physical inactivity. The main barriers to physical activity were work, household chores, and health problems. However, many respondents expressed their willingness to increase their physical activity frequency with some promotional policies. Walking was the most common physical activity practiced in the past year and the activity most respondents wanted to try in the future., Conclusions: Patients with CLD are insufficiently active and need physical activity interventions, especially regarding walking., (© 2023. Japanese Society of Gastroenterology.)

Background: The prognosis of cirrhosis is clearly stratified by liver function. Although direct-acting antiviral (DAA) has recently been used to eliminate hepatitis C virus (HCV), it is not clear whether liver function stratifies the prognosis of decompensated cirrhotic patients treated with DAA., Methods: A total of 206 HCV-associated decompensated cirrhotic patients who started DAA from February 2019 to December 2021 at 31 Japanese hospitals were prospectively registered., Results: The median age was 68, and the proportions of patients with Child-Pugh class A (CP-A), CP-B and CP-C were 10% (20/206), 76% (156/206) and 15% (30/206), respectively. Twenty-six patients died, and two patients underwent liver transplantation (LT); the 2- and 3-year LT-free survival rates were 90.0% and 83.2%, respectively. We examined factors associated with LT-free survival using 2 models including either CP class (Model 1) or MELD score (Model 2). In multivariate Cox proportional hazard analysis, CP class at 12 weeks after the end of treatment (EOT) in Model 1 and MELD score at 12 weeks after the EOT in Model 2 were significant factors, while baseline CP class or MELD score was not. Two-year LT-free survival rates were 100%, 91.6% and 60.4% for patients with CP-A, CP-B and CP-C at 12 weeks after the EOT and 95.2% and 69.6% for patients with MELD < 15 and MELD ≥ 15 at 12 weeks after the EOT, respectively., Conclusions: The prognosis of decompensated cirrhotic patients receiving DAA was stratified by liver function at 12 weeks after the EOT, not by baseline liver function., (© 2023. The Author(s).)

Background: Covert hepatic encephalopathy (CHE) adversely affects the clinical outcomes of patients with cirrhosis but remains largely undiagnosed and untreated. Although the Stroop test is a useful method for CHE detection, a faster, simpler, and more accurate test is required to diagnose CHE. This prospective study aimed to develop a new shortened Stroop test that can detect CHE and predict overt hepatic encephalopathy (OHE) in Japanese patients with cirrhosis., Methods: Patients who underwent neuropsychological tests (NPT) and the Stroop test between November 2018 and December 2021 were enrolled and followed until OHE occurrence or March 2022. The discriminative ability of various run combinations in the off and on states to detect CHE was evaluated using the area under the receiver-operating characteristic curve (AUC) and compared with that of the total Stroop test time., Results: Among the 227 eligible patients, the On1-2Time cutoff value of 44.4 s had a comparable discriminative ability with the total Stroop test time to detect CHE, with an AUC of 0.791, a sensitivity of 0.827, and a specificity of 0.685. During a median follow-up period of 16 months, 37 patients developed OHE. On1-2Time ≥ 44.4 s (hazard ratio [HR], 3.93; 95% confidence interval [CI] 1.36-11.36) and serum albumin levels (HR, 0.28; 95% CI 0.11-0.67) were independently associated with OHE occurrence., Conclusions: The shortened Stroop test (On1-2Time) is equivalent to the total Stroop test not only for identifying CHE but also for estimating the risk of progression to OHE., (© 2022. Japanese Society of Gastroenterology.)

Background: Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the impact of DAA therapy on liver-related events in patients with cirrhosis is unclear., Methods: A total of 350 patients with compensated and decompensated cirrhosis administered DAA therapy at 29 Japanese hospitals were enrolled (Child-Pugh class A [CP-A]: 195 patients, CP-B: 131 patients and CP-C: 24 patients)., Results: The SVR rates of patients with CP-A, CP-B and CP-C were 96.9%, 93.1% and 83.3%, respectively (p = 0.006). Seventy patients developed hepatocellular carcinoma (HCC), and male sex, previous HCC treatment, platelet counts < 10.0 × 10 4 /µl, alpha-fetoprotein levels ≥ 5.0 ng/ml and CP-C were identified as significant factors in the multivariate analysis. The cumulative HCC occurrence/recurrence rates at 1 year were 6.6%/45.2%. The cumulative rate of decompensated cirrhotic events requiring hospital admission at 1 year was 9.1%. In the multivariate analysis, CP-B and CP-C were identified as significant factors. During the median observation period of 14.9 months, 13 patients died and one patient received liver transplant. The overall survival rates at 1 year were 98.4% in patients with CP-A, 96.4% in those with CP-B and 85.6% in those with CP-C (CP-A vs. CP-B: p = 0.759, CP-A vs. CP-C: p = 0.001 and CP-B vs. CP-C: p = 0.005)., Conclusions: HCC development and mortality in patients with CP-B were not different from those with CP-A. On the other hand, in patients with CP-C, the development of HCC and decompensated cirrhotic events requiring hospital admission, and death were frequent., Trial Registration: University Hospital Medical Information Network (UMIN000036150)., (© 2022. Japanese Society of Gastroenterology.)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide, including in Japan. The Japanese Society of Gastroenterology (JSGE) and the Japanese Society of Hepatology (JSH) have established the Japanese NAFLD/NASH guidelines in 2014 and revised these guidelines in 2020. As described in these guidelines, weight reduction by diet and/or exercise therapy is important for the treatment of NAFLD patients. The I148M single nucleotide polymorphism (rs738409 C > G) of PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is widely known to be associated with the occurrence and progression of NAFLD. In the Japanese, the ratio of PNPLA3 gene polymorphisms found is approximately 20%, which is higher than that found in Westerners. In addition, the ratio of lean NAFLD patients is also higher in Japan than in Western countries. Therefore, the method for lifestyle guidance for the NAFLD patients in Japan would be different from that for the people in Western countries. The problems in the treatment of NAFLD patients include alcohol consumption and sarcopenia. Therefore, guidelines that can help clinicians treat Japanese patients with NAFLD are needed. In this expert review, we summarize evidence-based interventions for lifestyle modification (diet, exercise, alcohol, and sarcopenia) for the treatment of patients with NAFLD, especially from Japan and Asian countries., (© 2021. Japanese Society of Gastroenterology.)

Background: The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated., Methods: A nationwide survey was performed for patients with ACLF occurring between 2017 and 2019. Cirrhotic patients with a Child-Pugh score of 5-9 were diagnosed as having ACLF when liver failure (serum bilirubin level of ≥ 5.0 mg/dL and a prothrombin time international normalization rate [INR] of ≥ 1.5) occurred within 28 days after an acute insult. Patients who fulfilled either criterion (total serum bilirubin or INR) and/or those with indeterminate Child-Pugh scores at baseline were also enrolled., Results: Among the 501 enrolled patients, 183 patients (37%) were diagnosed as having ACLF. The etiologies of the cirrhosis and acute insults were alcohol intake/abuse in 114 (62%) and 75 (41%) patients, respectively. Sixty-eight patients (37%) were also diagnosed as having severe alcoholic hepatitis. The survival rate without liver transplantation was 48% among the ACLF patients and 71% in the remaining patients (P < 0.01). A multivariate analysis revealed that the disease condition was significantly associated with mortality, with an odds ratio of 2.025 in ACLF patients relative to the remaining patients (P < 0.01), and patient age and the number of organs with functional failure were also associated with mortality among the ACLF patients., Conclusion: The proposed diagnostic criteria for ACLF were useful for identifying cirrhotic patients with an unfavorable outcome following acute insults. A therapeutic strategy for patients with severe alcoholic hepatitis should be established, since such patients accounted for the majority of ACLF patients., (© 2021. Japanese Society of Gastroenterology.)

Background: The JSGE/JSH guidelines for the management of patients with liver cirrhosis revised in 2020 recommends new strategies for nutritional assessment and intervention, although their usefulness in daily clinical practice is unclear., Methods: A total of 769 patients with cirrhosis were classified into low-, intermediate-, and high-risk groups according to hypoalbuminemia and sarcopenia, the criteria established for initiating the nutritional therapy algorithm in the guidelines. The association between these groups and mortality was analyzed using a Cox proportional hazards model. The effect of branched-chain amino acids (BCAAs) on survival was evaluated using propensity score matching., Results: Of the enrolled patients, 495 (64%) were men with a median age of 73 years, 428 (56%) had hypoalbuminemia, 156 (20%) had sarcopenia, and 288 (37%) were receiving BCAAs. During a median follow-up period of 1.5 years, 276 (36%) patients died. The intermediate-risk [hazard ratio (HR), 1.60; 95% confidence interval (CI), 1.18-2.18] and high-risk (HR, 2.85; 95% CI, 1.92-4.23) groups independently predicted mortality. Among the propensity score-matched 250 patients, 49 (39%) BCAA-treated and 58 (46%) untreated died. Overall survival was higher in BCAA-treated patients than in untreated patients (HR, 0.67; 95% CI, 0.46-0.98). The survival benefit of BCAAs was pronounced in the intermediate-risk (HR, 0.50; 95% CI, 0.31-0.80) and high-risk (HR, 0.38; 95% CI, 0.16-0.91) groups., Conclusions: The 2020 JSGE/JSH guidelines for liver cirrhosis are useful in stratifying the mortality risk and providing effective nutritional interventions for malnourished patients with cirrhosis., (© 2021. Japanese Society of Gastroenterology.)

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH., (© 2021. The Author(s).)

Background: Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan., Methods: A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT)., Results: The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child-Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child-Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl., Conclusions: Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

Background: We previously reported that the incidence of hepatocellular carcinoma (HCC) with non-viral etiologies increased rapidly between 1991 and 2010 in Japan., Methods: To update this investigation, we enrolled patients who were initially diagnosed as having non-B, non-C HCC at participating hospitals between 2011 and 2015. In addition to the patient characteristics investigated in the previous report, we also investigated the duration of alcohol consumption. The overall survival rate was analyzed using the Kaplan-Meier method, and the hazard function against the body mass index (BMI) was plotted using cubic splines., Results: A total of 2087 patients were enrolled. The proportion of patients with non-viral etiologies has continued to increase from 10.0% in 1991 to 32.5% in 2015. Patients were also older (median ages, 70-73 years) and more obese (median BMIs, 23.9-24.2 kg/m 2 ), and the proportions of patients with diabetes mellitus (46.1% to 51.6%), hypertension (42.7% to 58.6%), dyslipidemia (14.6% to 22.9%), and fatty liver (24.0% to 28.8%) had all increased significantly. There was a significant inverse relationship between the duration and the amount of daily alcohol consumption. The improvement in the overall survival was relatively small, with a decreased proportion of patients under surveillance (41.3% to 31.6%). A hazard function plot showed a curve similar to that in our previous report, with a lowest hazard of ~ 26 kg/m 2 ., Conclusions: The proportion of HCC patients with non-viral etiologies continues to increase in Japan. Lifetime total amount of alcohol consumption may be a risk factor.

Background: A nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan., Methods: Two-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys., Results: In total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation)., Conclusion: Although the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years.

Background: In Japan and Europe, a retrieval basket is generally used for endoscopic extraction of bile duct stones, while in the US, a retrieval balloon is mainly used. However, the efficacies of these two devices have not been previously compared. Therefore, the present multicenter, prospective, randomized study was performed to compare the efficacies of these two devices for endoscopic biliary stone extraction., Methods: This study was designed as a non-inferiority study in comparing a basket removal with a balloon removal. Six Japanese institutions participated in this study, which included 184 patients with bile duct stones <11 mm in diameter with no limitation in the number of stones. The stones were identified and measured during ERCP, after which the patients were randomly assigned to undergo endoscopic stone extraction using either a basket catheter or a balloon catheter. The primary end point was the rate of complete removals of stones within 10 min, and the secondary end point was the rate of procedure-related complications., Results: There were 91 patients in the basket group and 93 in the balloon group. The rate of successful stone extraction within 10 min was 81.3 % (74/91) in the basket group and 83.9 % (78/93) in the balloon group (p = 0.7000). The complication rate was 6.6 % in the basket group and 11.8 % in the balloon group (p = 0.3092). Complications included bleeding, pancreatitis, and cholangitis., Conclusions: Basket and balloon catheters showed similar efficacies for endoscopic biliary stone extraction when stone size is 11 mm or smaller.

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.

Background: Endoscopic sphincterotomy (ES) is widely performed in patients with common bile duct stones (CBDS). However, the long-term outcomes of patients following ES have not been sufficiently elucidated. Impaired papillary function following ES may result in additional late complications. In contrast, endoscopic papillary balloon dilation (EPBD)-another option for treating CBDS-is expected to preserve papillary function. This study aimed to compare the long-term outcomes of patients with CBDS treated with ES to those treated with EPBD in a large cohort. In addition, a subgroup analysis was performed, according to gallbladder (GB) status., Methods: A cohort study was performed using propensity score matching to reduce treatment selection bias. This involved the analysis of follow-up data for 1086 patients who underwent EPBD or ES for CBDS., Results: Propensity score matching extracted 246 pairs of patients. The median (interquartile range) follow-up period after EPBD or ES was 93.5 (46.8-129.2) months and 90 (42-139.3) months, respectively. The incidence of CBDS recurrence after EPBD and ES were 8.5 and 15.0 %, respectively. The hazard ratio (95 % CI) was 0.577 (0.338-0.986) (P = 0.044). Based on the status of the GB, the incidence of CBDS recurrence was significantly different between post-EPBD and post-ES in the group with cholecystectomy after EPBD/ES (P = 0.013)., Conclusions: The incidence of biliary complications was significantly lower in patients after EPBD than in those after ES, and this outcome appeared most markedly in patients who also underwent cholecystectomy.

Background: Although guidelines in Japan recommend the cessation of antithrombotic agents before endoscopic biopsy, the safety of biopsy without the cessation of these agents has not been evaluated to date in this country. Therefore, we aimed to assess the feasibility of biopsy without cessation of antithrombotic agents in Japan., Methods: This was a prospective single-arm study from a single institution. From May 2010 to November 2011, 112 outpatients who were receiving antithrombotic agents because of their high-risk status for a thromboembolic event (after implantation of coronary stent, after valve replacement, or a previous history of thromboembolic event or heart failure due to atrial fibrillation) were enrolled. We evaluated the rate of severe bleeding complications within 2 weeks after endoscopy and the endoscopic bleeding time (EBT) after biopsy in patients who underwent biopsy for endoscopic findings requiring pathology assessment., Results: Among the 112 participants, 101 biopsies were performed for 48 and 12 outpatients who had had esophagogastroduodenoscopy and colonoscopy, respectively. All the biopsies provided enough specimens to evaluate pathologically. Hemostasis after biopsy was confirmed for all biopsies during endoscopic observation. No patients complained of any bleeding symptoms in the 2-week observation period after biopsy (0/101; 95% confidence interval [CI] 0-3.6%). Concerning the EBT (median 2.2 ± 1.8 min, range 0.5-9 min), there were no significant differences between patients receiving single antithrombotic agents and those receiving multiple agents (2.4 ± 1.4 vs. 2.1 ± 2.1 min), nor were there any significant differences between patients not receiving and receiving warfarin (2.3 ± 1.8 vs. 2.2 ± 1.8 min)., Conclusion: Biopsy without cessation of antithrombotic agents, as recommended in Western guidelines, can also be acceptable for Japanese people if performed carefully.

The interpretation of colonic biopsies related to inflammatory conditions can be challenging because the colorectal mucosa has a limited repertoire of morphologic responses to various injurious agents. Only few processes have specific diagnostic features, and many of the various histological patterns reflect severity and duration of the disease. Importantly the correlation with endoscopic and clinical information is often cardinal to arrive at a specific diagnosis in many cases.

With regard to the esophagus, the term "squamous dysplasia" has been used in European countries, the United States, and China, while its use is controversial in Japan. Recently, "low-grade intraepithelial neoplasia" and "high-grade intraepithelial neoplasia" have been used as inclusive terms for dysplasia and carcinoma in situ in the World Health Organization classification. Endoscopically, it is often difficult to identify squamous intraepithelial neoplasia by conventional endoscopy, but application of iodine is useful for the diagnosis of such a lesion. In addition, new types of endoscopic techniques, including magnifying endoscopy, narrow-band imaging (NBI), and endocytoscopy are helpful to detect squamous intraepithelial neoplasia. NBI is very useful for identifying the intrapapillary capillary loop pattern. Regarding the pathological criteria of squamous dysplasia and squamous cell carcinoma, the views of Japanese and Western pathologists have differed significantly. Before the term "intraepithelial neoplasia" was introduced, severe dysplasia as diagnosed by Western pathologists was in fact the same as squamous cell carcinoma in situ or noninvasive carcinoma as diagnosed by Japanese pathologists. This problem has been solved by the introduction of the Vienna classification; however, there are still some issues that need to be resolved. One of them is the presence of basal layer type squamous cell carcinoma in situ, which is often underdiagnosed as lowgrade intraepithelial neoplasia by Western pathologists. Endoscopic treatments such as endoscopic mucosal resection and endoscopic submucosal dissection have recently become possible choices for squamous intraepithelial neoplasia; however, these techniques are not in widespread use in the West. We believe that a consensus meeting between Japanese and Western pathologists as well as endoscopists should be held promptly to reach a common ground for the nomenclature.

Background: The development of equipment and contrast agents for ultrasound imaging has contributed to major breakthroughs in the diagnosis of pancreatic tumors. We aimed to determine the diagnostic effectiveness of contrast ultrasound with Levovist, using the Agent Detection Imaging (ADI) technique, in 50 patients with pancreatic tumors., Methods: We studied 50 cases of histologically proven pancreatic disease; 39 carcinomas, 2 endocrine tumors, 4 intraductal papillary mucinous carcinomas (IPMCs), and 5 cases of tumor-forming pancreatitis (TFP). Vascular and perfusion images of contrast-enhanced ultrasound (CE-US) were used for the evaluation of tumor vascularity and parenchymal perfusion of the tumor, respectively. The hemodynamics of the tumor, and the diagnostic capacity of CE-US were compared with those shown by computed tomography (CT). The histological diagnosis in all cases was made from either biopsy or surgical specimens., Results: Thirty-four cases of pancreatic carcinoma (87%) showed a hypovascular and hypoperfusion pattern. The endocrine tumors showed a heterogeneous hypervascular and hyperperfusion pattern. All IPMC cases showed hypervascularity of the nodules inside the tumors. TFP showed an isovascular and homogeneous isoperfusion pattern. When tumors showing a hypovascular or hypoperfusion pattern on CE-US were diagnosed as carcinomas, 34 of the 39 carcinomas (87%) fit this criterion, with a 95% confidence interval (CI) of 73%-96%, whereas, on CT, 31 of the 39 were diagnosed as carcinoma; (sensitivity, 79%). The sensitivity and accuracy of CT were inferior to those of CE-US. Results of comparison between the CE-US findings and the histological diagnosis were as follows. The one papillary adenocarcinoma showed a hypervascular and hyperperfusion pattern; the 32 well or moderately differentiated adenocarcinomas showed a hypovascular and hypoperfusion pattern; and in the poorly differentiated adenocarcinomas, 2 cases of scirrhous type showed a hypovascular and hypoperfusion pattern, and the 4 cases of medullary type showed an isovascular and isoperfusion pattern., Conclusions: The differences in vascularity of pancreatic carcinomas depicted by CE-US were associated well with differences in histology. CE-US, by the ADI technique, is useful for the diagnosis of pancreatic tumors.