Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis

Background: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. Methods: Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. Results: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001). Conclusions: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production

Dried Feces Spots as an Alternative DNA Source : Detection of K-ras Mutations in Colorectal Cancer Screening

Detection of genetic alterations in exfoliated intestinal cells into feces is expected to be a novel approach to colorectal cancer screening. We aimed here to detect cancer-related gene mutations in routine fecal specimen; dried feces spots (DFS) on a filter paper especially designated for an automated fecal occult blood (FOB) test. DNA was simply extracted from a 3 mm disc of DFS (including around 10 mg feces) with a boiling procedure followed by a cationic surfactant extraction. K-ras common mutations, as the typical cancer-related gene alterations, were detected with a nested allele specific PCR with microfluorometry (ASP/MFL). Adequate DNA was recovered from 363/451 (80.5%) DFS specimens tested. The K-ras mutations were detected in 2/24 (8.3%) from patients with colorectal cancer and 13/315 (4.1%) from screening participants with positive FOB. No mutations were detected in 24 DFS specimens with negative FOB. The results of K-ras mutation frequency were not encouraging to achieve practically a specific dreliable method for colorectal cancer screening. However this report, identifying for the first time a cancer related gene alteration in feces using identical samples with routine FOB test, will be a step to realize a molecular genetic testing for the cancer screening

The Usefulness of the Alpha-Retroflex Position in Biliary Cannulation on Single-Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Roux-en-Y Gastrectomy: A Retrospective Study

Introduction. Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is a useful therapeutic procedure that provides promising results in patients with surgically altered anatomy. However, biliary cannulation in BE-ERCP remains challenging. Therefore, in patients with Roux-en-Y gastrectomy, this study aimed to evaluate a BE-ERCP cannulation strategy that includes the newly developed alpha-retroflex scope position. Methods. This was a retrospective review of 52 patients with Roux-en-Y gastrectomy who underwent BE-ERCP at two centers between April 2017 and December 2022. In these patients, three types of scope position had been used for biliary cannulation: straight (S-position), J-retroflex (J-position), and alpha-retroflex (A-position). First, the S-position was used for biliary cannulation. Then, if biliary cannulation was difficult with this position, the J-position was used, followed by the A-position, if necessary. Results. The biliary cannulation success rate was 96.6% (50/52). The S-, J-, and A-positions achieved successful biliary cannulation in 24 (48%), 14 (28%), and 12 patients (24%), respectively. No adverse events, including post-ERCP pancreatitis and perforation, occurred. Conclusion. This was the first study of a cannulation strategy that included the A-position in addition to the S- and J-positions. The study showed that the A-position is feasible and safe in BE-ERCP in patients with Roux-en-Y gastrectomy

Peroral Cholangioscopy-Guided Targeted Biopsy versus Conventional Endoscopic Transpapillary Forceps Biopsy for Biliary Stricture with Suspected Bile Duct Cancer

Background: The recent improvement of peroral cholangioscopy (POCS) maneuverability has enabled the precise, targeted biopsy of bile duct lesions under direct cholangioscopic vision. However, as only small-cup biopsy forceps can pass through the scope channel, the resulting small sample size may limit the pathological diagnosis of biopsy specimens. This study compared the diagnostic abilities of POCS-guided biopsy and conventional fluoroscopy-guided biopsy for bile duct cancer. Method: This multicenter, retrospective cohort study included patients exhibiting bile duct stricture with suspected cholangiocarcinoma in whom POCS-guided and fluoroscopy-guided biopsies were performed in the same session. The primary endpoint was the diagnostic sensitivity for malignancy. The size and quality of the biopsy specimens were also compared. Result: A total of 59 patients were enrolled. The sensitivity of POCS-guided biopsy was similar to that of fluoroscopy-guided biopsy (54.0% and 64.0%, respectively). However, when the modalities were combined, the sensitivity increased to 80.0%. The mean specimen size from POCS-guided biopsy was significantly smaller than that from fluoroscopy-guided biopsy. The specimen quality using fluoroscopy-guided biopsy was also better than that using POCS-guided biopsy. Conclusions: The diagnostic sensitivity of POCS-guided biopsy is still insufficient, mainly because of the limited specimen quantity and quality. Therefore, conventional fluoroscopy-guided biopsy would be helpful to improve diagnostic sensitivity

Rotational hypermobility of disc wedging using kinematic CT: preliminary study to investigate the instability of discs in degenerated scoliosis in the lumbar spine

The number of patients showing lumbar degenerative scoliosis, including disc wedging, has increased, and examination of the mechanism of spinal nerve compression due to lateral and rotational mobility of the lumbar spine is necessary. Thirty-two patients with L4–L5 disc wedging but without antero- or retrospondylolisthesis and ten age-matched controls were examined. The angle of disc wedging and change in the angle between left and right bending were evaluated by anterior–posterior X-ray images of patients while they were in a standing position. The degree of disc degeneration and existence of vacuum phenomena were evaluated at the L4–L5 discs. Rotational mobility between maximal right and left rotation was examined by computed tomography (CT). Rotational mobility was measured using the spinal transverse processes of L4 and L5. The relationship between these factors was statistically evaluated using multivariate analysis and Spearman’s correlation test. There was a significant increase in the average rotational mobility of the L4–L5 disc-wedging group. In the L4–L5 disc-wedging group, the increased angle of disc wedging and change in the angle between left and right bending correlated with increased rotational mobility. The degree of disc degeneration did not affect rotational mobility. However, existence of vacuum phenomena increased the rotational mobility of the L4–L5 disc-wedging group. This is the first study to evaluate the rotational hypermobility of L4–L5 disc wedging in patients without antero- or retrospondylolisthesis using kinematic CT. Increases in the wedging angle and abnormal instability of lateral bending correlated with increased rotational mobility. For surgical planning of degenerative L4–L5 disc wedging, it is important to consider rotational hypermobility using kinematic CT or X-ray imaging findings of lateral bending