Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2014 to 2018 in Japan: A large-scale multicenter retrospective study.

AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan. METHODS: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score. RESULTS: A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively. CONCLUSIONS: The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%-2%.

Pemafibrate improves liver dysfunction and non-invasive surrogates for liver fibrosis in patients with non-alcoholic fatty liver disease with hypertriglyceridemia: a multicenter study.

BACKGROUND: This retrospective, multicenter study evaluated the effect of pemafibrate treatment on liver function and fibrosis by liver function tests (LFTs) and various fibrotic biomarkers including FibroScan in non-alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia. METHODS: A total of 138 NAFLD patients treated with pemafibrate at three hospitals between September 2018 and April 2021 were included. To evaluate the effect of pemafibrate treatment, FibroScan-aspartate aminotransferase (FAST) score, a novel index of steatohepatitis that can be calculated based on the aspartate aminotransferase (AST) value, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) was used. RESULTS: Serum TG levels were significantly decreased 4 weeks after pemafibrate treatment (p = 0.003). The levels of AST (p = 0.038), alanine aminotransferase (ALT) (p = 0.003), and gamma-glutamyl transferase (GGT) (p = 0.047) also significantly diminished 12 weeks after pemafibrate administration compared to before administration (p < 0.05). However, serum HDL-cholesterol (p = 0.193), LDL-cholesterol (p = 0.967), and eGFR (p = 0.909) levels were not significantly altered 12 weeks after pemafibrate administration. In addition, the fibrosis biomarkers' Type IV collagen (p = 0.753) and FIB-4 index (p = 0.333) did not significantly differ, while Autotaxin (p = 0.006) and the AST-to-platelet ratio index (APRI) (p = 0.003) significantly decreased 48 weeks after pemafibrate administration. No significant reductions in LSM (p = 0.959) and CAP (p = 0.266) were detected using FibroScan 48 weeks after pemafibrate administration. FAST score was significantly improved (p = 0.0475). CONCLUSION: Pemafibrate improved LFTs, including fibrotic biomarkers and FAST score, due to the hepatic anti-inflammatory effect, suggesting that pemafibrate may prevent disease progression in NAFLD patients with hypertriglyceridemia.

HbA1c of 5.8% or higher as the most useful indicator for recommendation of ultrasonography to detect nonalcoholic fatty liver disease.

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. This study was performed to examine the association between NAFLD and each factor of metabolic syndrome and to identify the factors that are most strongly associated with NAFLD in participants undergoing health checkups. Methods: We studied 6538 participants who underwent a health checkup from 2017 to 2018 in our institution. Participants with alcohol intake exceeding 20 g/day or with other chronic liver diseases were excluded. Fatty liver was detected by ultrasonography. Results: In total, 4310 participants were enrolled, and 28.4% had fatty liver (NAFLD). The prevalence of NAFLD was highest in the diabetes mellitus (DM)-only group than in the dyslipidemia-only or hypertension-only group. The DM-only group was the only group whose prevalence of NAFLD was >50% in the overall study and in males. The prevalence of NAFLD was higher in males than in females in the DM-only, hypertension-only, and dyslipidemia-only groups. The prevalence of NAFLD was >70% in the dyslipidemia and DM combined group. Multivariate analysis showed that gender and HbA1c were the independent factors most strongly associated with NAFLD. The cutoff value for HbA1c by receiver operating characteristic curve analysis was 5.8% (sensitivity, 57.9%; specificity, 72.6%; area under the curve, 0.70). Conclusion: NAFLD was most strongly associated with DM, among the various components of metabolic syndrome. We strongly recommend abdominal ultrasonography to detect NAFLD in patients with an HbA1c of ≥5.8% in general practice and during health checkups.

Xanthogranulomatous pancreatitis mimicking a malignant cystic tumor of the pancreas: report of a case.

Xanthogranulomatous pancreatitis (XGP) is a rare inflammatory disease of the pancreas. A correct diagnosis is usually made only after pathological examination. A 76-year-old man was referred to our hospital for investigation of erythroderma, muscle weakness, and weight loss. We suspected dermatomyositis as a paraneoplastic phenomenon and investigated accordingly. Computed tomography showed a cystic lesion encapsulated by a thick wall in the pancreatic body. On magnetic resonance imaging, the lesion had low intensity on the T1-weighted images and heterogeneously high intensity on the T2-weighted images. (18)F-Fluorodeoxyglucose positron emission tomography showed abnormal uptake with a maximum standardized uptake value of 9.1. Based on these findings, we made a preoperative diagnosis of intraductal papillary-mucinous carcinoma and performed a distal pancreatectomy. Macroscopically, the cyst was surrounded by a yellow-tan mass with an unclear border, and was filled with hemorrhagic and necrotic tissue. Microscopically, the mass contained an aggregation of many foamy histiocytes, lymphocytes, and plasma cells. These microscopic findings were consistent with xanthogranulomatous inflammation, and the lesion was diagnosed as XGP. Although it is a rare benign pancreatic lesion, XGP should nevertheless be considered in the differential diagnosis of cystic lesions of the pancreas.

Extracorporeal abdominal massage may help prevent recurrent bile duct stones after endoscopic sphincterotomy.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy (EST) is effective, but recurrent bile duct stones are a common late complication. Because there are still no effective therapies for preventing this complication, some patients have experienced bile duct stone recurrence many times. We describe herein a method of abdominal massage to treat patients with prior cholecystectomy who have experienced recurrence of bile duct stones.

Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo.

Galectin-9, a soluble ß-galactoside-binding animal lectin, evokes apoptosis in various human cancer cell lines. The galectin-9 antitumor effect against hepatocellular carcinoma (HCC) is, however, unknown. We investigated whether galectin-9 suppresses HCC growth in vitro and in vivo. We assessed the antitumor effect of galectin-9 on HCC cells by conducting WST-8 assay in vitro and xenograft model analysis in vivo. Galectin-9-induced apoptosis was evaluated by FACS and ELISA in vitro and by TUNEL stain in vivo. Cell cycle alteration was profiled by FACS. Caspases were profiled by colorimetry. MicroRNAs related to the galectin-9 antitumor effects were determined using microarrays, and their antitumor effect was confirmed in a transfection study in vitro. The expression levels of the target proteins of the miRNAs extracted above were analyzed by western blot analysis. To summarize the results, galectin-9 inhibited the growth of the HCC cell lines HLE and Li-7 in vitro and Li-7 in vivo inducing apoptosis. Cell cycle turnover was not arrested in HLE and Li-7 cells in vitro. miR-1246 was similarly extracted both in vitro and in vivo, which sensitized Li-7 cells to apoptosis when transfected into the cells. DYRK1A, a target protein of miR-1246 was downregulated in Li-7 cells. Caspase-9 was upregulated in Li-7 cells in vitro and in vivo. In conclusion, galectin-9 inhibited the growth of HCC cells by apoptosis, but not cell cycle arrest, in vitro and in vivo. miR-1246 mediated signals of galectin-9, possibly through miR-1246-DYRK1A-caspase-9 axis. Galectin-9 might be a candidate agent for HCC chemotherapy.

MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. microRNAs (miRNAs) are small non-coding RNAs that negatively regulate messenger RNA (mRNA). Recently, it was demonstrated that the aberrant expression of certain miRNAs plays a pivotal role in liver disease. The aim of the present study was to evaluate changes in miRNA profiles associated with metformin treatment in a NASH model. Eight-week-old male mice were fed a methionine- and choline-deficient (MCD) diet alone or with 0.08% metformin for 15 weeks. Metformin significantly downregulated the level of plasma transaminases and attenuated hepatic steatosis and liver fibrosis. The expression of miRNA-376a, miRNA­127, miRNA-34a, miRNA-300 and miRNA-342-3p was enhanced among the 71 upregulated miRNAs, and the expression of miRNA-122, miRNA-194, miRNA-101b and miRNA-705 was decreased among 60 downregulated miRNAs in the liver of MCD-fed mice when compared with control mice. Of note, miRNA profiles were altered following treatment with metformin in MCD-fed mice. miRNA-376a, miRNA­127, miRNA-34a, miRNA-300 and miRNA-342-3p were downregulated, but miRNA-122, miRNA-194, miRNA­101b and miRNA-705 were significantly upregulated in MCD-fed mice treated with metformin. miRNA profiles were altered in MCD-fed mice and metformin attenuated this effect on miRNA expression. Therefore, miRNA profiles are a potential tool that may be utilized to clarify the mechanism behind the metformin-induced improvement of hepatic steatosis and liver fibrosis. Furthermore, identification of targetable miRNAs may be used as a novel therapy in human NASH.

Expression profiles of 507 proteins from a biotin label-based antibody array in human colorectal cancer.

Molecular-targeted therapy is one of the most promising therapies for patients with advanced-stage colorectal cancer (CRC). However, a wide range of proteins have unknown expression levels in CRC. The purpose of the present study was to determine the expression levels of various proteins related to colorectal carcinogenesis and cancer development. We examined the expression levels of 507 target proteins using a biotin label-based antibody array in 6 human CRC tissues. We also analyzed the clinicopathological features of CRC patients. In CRC tissues, IL-1α, GRO, Glut5, MIG, ICAM-5, VE-cadherin, uPA and Leptin R were increased when compared to levels in normal colon tissues. MPIF-1/CCL23, FGF R5, MIP2, SAA and IL-18 Rß were strongly upregulated in rectal cancer when compared to the levels in non-rectal cancer. These data suggest that differential protein expression profiles exist under different conditions, including carcinogenesis and CRC localization. Therefore, an exhaustive analysis of protein expression levels using a biotin label-based antibody protein array is a potentially useful tool for identifying novel individual therapies for CRC patients.