Hajime Isomoto’s research while affiliated with Tottori University and other places

Although hyperuricemia is associated with chronic kidney disease (CKD), the impact of uric acid (UA)-lowering drugs on CKD has been controversial. Previous investigations have primarily included xanthine oxidase inhibitors; therefore, research of dotinurad, a recently developed selective urate reabsorption inhibitor, is necessary. This retrospective study included 58 patients with CKD; of these, 29 newly initiated dotinurad and 29 initiated febuxostat. The effects of dotinurad and febuxostat on the serum UA, urinary UA-to-creatinine ratio (UUCR), and estimated glomerular filtration rate (eGFR) during 3 months were analyzed to compare their impacts on renal function. Dotinurad and febuxostat decreased serum UA (8.40 ± 1.11 to 6.50 ± 0.80 mg/dL [p < 0.001] and 8.91 ± 1.21 to 6.05 ± 1.28 mg/dL [p = < 0.001], respectively). The UUCR increased after dotinurad (0.35 ± 0.15 to 0.40 ± 0.21 g/gCr [p = 0.024]); however, it decreased after febuxostat (0.33 ± 0.12 to 0.21 ± 0.06 g/gCr [p = 0.002]). The eGFR improved after dotinurad (33.9 ± 15.2 to 36.2 ± 15.9 mL/min/1.73 m² [p < 0.001]). No change was observed after febuxostat treatment (33.4 ± 19.6 to 34.1 ± 21.6 mL/min/1.73 m²). Renal function improved only with dotinurad, thus highlighting its renoprotective effects beyond the reduction of serum UA.

Objective Although pancreatic ductal adenocarcinoma (PDAC) is still a devastating disease, the survival rate for surgically removed PDACs has significantly improved in recent years. Early detection is essential in managing PDAC. Summary Background Data The presence of KRAS mutations in PDAC leads to the initial genetic abnormality and offers a significant timeframe for identifying resectable PDACs. A minimally invasive and highly specific PDAC screening test is necessary to prevent the need for invasive follow-up tests. Methods Between July 2021 and March 2023, 169 cases were enrolled in 7 institutions. By administering secretin before esophagogastroduodenoscopy (EGD), the excretion of pancreatic juice into the papillary fluid can be stimulated, creating a resource for testing. Washing fluid was collected using a specialized catheter from control individuals ( n =75) and patients with resectable PDAC ( n =89) at the initial diagnosis. A highly sensitive technique was employed to study KRAS gene mutations. Results This study obtained an AUC of 0.934 [95%CI: 0.904, 0.964] when using KRAS mutations in duodenal lavage fluid to differentiate between patients with resectable PDAC and healthy controls. The estimated sensitivities were calculated with specificity set at 100%, resulting in a sensitivity of 83.1% [95%CI: 71.7%, 91.2%]. The McNemer test showed a significantly higher sensitivity for KRAS mutations than serum CEA and CA19-9 ( P <0.0001). Conclusions We created a method to identify resectable PDACs by analyzing KRAS mutation levels in duodenal fluid collected during EGD with secretin stimulation of pancreatic juice secretion.

Background and Aim In recent years, there has been a rise in cryptogenic hepatocellular carcinoma (c‐HCC) cases in Japan, posing a detection challenge due to an unknown etiology. This study aims to enhance diagnostic strategies for c‐HCC by analyzing its characteristics and exploring current opportunities for detection. Methods A retrospective study was conducted from April 2012 to March 2022, enrolling 372 newly diagnosed hepatocellular carcinoma (HCC) patients. Excluding cases associated with hepatitis viral infection, alcoholic liver disease, non‐alcoholic fatty liver disease/steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and congestive hepatopathy, the study specifically focused on genuine c‐HCC. The analysis delved into the characteristics, detection opportunities, and survival outcomes associated with c‐HCC. Results Among the non‐viral HCC cases, 55 patients (29.3%) (34 men and 21 women) were diagnosed with c‐HCC, making it the second‐highest etiology. Notably, individuals with c‐HCC, typically aged 60 and above (median age 76.0), exhibited a women predominance and presented with larger tumors (4.5 cm vs. 2.5 cm), correlating with a poorer prognosis. Cirrhosis was notably absent in most c‐HCC cases (72.7%), and more than half (56.4%) did not have diabetes mellitus (DM). Diagnostic pathways for c‐HCC primarily involved incidental imaging (47%) and symptoms (24%). Within the cohort of c‐HCC, the prognosis for symptomatic cases is notably unfavorable compared to other cases [median survival time 19.0 (7.0–45.0) months vs. 47.0 (29.0–76.0) months, p = 0.029]. In the multivariate regression analysis, age and women emerged as independent factors associated with c‐HCC. Rather than a significant increase in women, there is a narrowing gender gap. Conclusion Patients with c‐HCC were predominantly elderly, without cirrhosis or diabetes, and exhibited minimal gender differences. Detection often occurred incidentally through abdominal imaging. Considering the limitations of conventional surveillance, it seems reasonable to propose that abdominal imaging be included in cancer screening, particularly for individuals aged 60 and older. Trial Registration 1610A127

Background To investigate the effects of colonoscopic administration of probiotics on patients with irritable bowel syndrome with predominant diarrhea (IBS-D) by a single-center, randomized-controlled trial. Methods Consecutive outpatients at the First Affiliated Hospital of Fujian Medical University who met the Rome IV diagnostic criteria for IBS-D (n = 22) and healthy subjects (n = 10) from January 2017 to January 2018 were enrolled. IBS-D patients were randomly divided into either the probiotics or the placebo group. During the colonoscopy examination, a suspension of live combined Bifidobacterium with Lactobacillus tablets and normal saline was sprayed into the right colon of patients in the probiotics and the placebo group, respectively. All subjects’ clinical data and stool samples were collected before, 2 weeks and 4 weeks after colonoscopic treatment. Results Twenty-nine subjects completed the follow-up. A significant difference was found in the frequency of defecation at 2 weeks, and the abdominal Visual Analog Score and Bristol stool scale at 4 weeks after probiotics treatment. The gastrointestinal symptom rating scale and IBS severity score decreased significantly and the IBS Quality of Life Instrument score increased 2 weeks after probiotics treatment (p < 0.05). The comprehensive therapeutic index was 70.0% and 44.4% in the probiotics group and the placebo group, respectively. The gut microbiota diversity was not significantly different at 2 and 4 weeks after treatment among the groups. Ratio of Firmicutes to Bacteroidetes decreased in the probiotics group. Conclusions The symptoms of IBS-D could be improved by probiotics administration via colonoscopy. The study was registered on chictr.org.cn (ChiCTR-IPR-17010411). Graphical Abstract

Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed over a median follow-up of 614 days. Results: HIF-PHI and ESA significantly increased the hemoglobin levels within 6 months of treatment (9.5 ± 1.0 to 10.7 ± 1.1, p < 0.01, and 9.9 ± 1.5 to 10.7 ± 1.2 g/dL, p < 0.01, respectively). The HIF-PHI group demonstrated a significant decrease in red cell distribution width (14.5 ± 1.9% to 13.8 ± 1.4%, p < 0.01), suggesting improved erythropoiesis, and exhibited a lower cumulative incidence of outcomes. The aged-adjusted multivariate analysis confirmed the independent association between HIF-PHI treatment and reduced risk of cumulative outcome (p = 0.042). Conclusions: HIF-PHIs can serve as an alternative to ESA for managing renal anemia in CKD, improving both hematological parameters and long-term outcomes.

Background: Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can progress to gastric cancer through atrophic gastritis (AG). The risk of gastric cancer increases with the progression of AG. Therefore, investigating the risk factors for the progression of AG is important. Methods: Using the GTEx and GEO databases, we extracted thirty-four candidate genes involved in the progression of AG. Then, with in silico analysis using HaploReg v4.1 and JASPAR (Matrix ID: MA0113.3), we extracted rs1231760 of RGS2 as a key single-nucleotide polymorphism (SNP) that could be involved in the functional change in the candidate gene. A correlation analysis between the selected SNP and AG in 200 H. pylori-positive and 302 H. pylori-negative participants was conducted. For functional analysis of the SNP, a dual-luciferase assay using reporter plasmids with a major or minor allele sequence was carried out. Results: The frequency of the C/C genotype of rs1231760 was higher in the AG group than in the non-AG group (p = 0.0471). Functional analysis showed that the transcriptional activities were higher at the dexamethasone-stimulating C allele than at the others (p < 0.05). Conclusions: The C/C genotype of rs1231760 in RGS2 could be a biomarker of high-risk H. pylori-positive AG because of an increase in RGS2 expression.

Adjusting the dosage of renal excretory drugs according to the patient’s renal function is essential. Vancomycin necessitates such adjustments due to its potential to cause nephrotoxicity when administered in excess. Creatinine-based equations for assessing the glomerular filtration rate, such as the Cockcroft-Gault and Modification of Diet in Renal Disease equations, are often used for dosage adjustments. However, vancomycin-induced nephrotoxicity sometimes occurs in critically ill patients, even in those with a normal estimated glomerular filtration rate. This case involved a 64-year-old male with cholangitis who developed vancomycin-induced nephrotoxicity. The patient was sarcopenic and had multiple risk factors that predisposed him to drug-induced nephrotoxicity. Moreover, creatinine-based equations may lead to the overestimation of glomerular filtration rate and subsequent vancomycin overdose. This case underscores the need for careful interpretation of creatinine-based assessments. We propose strategies to optimize medication dosing, particularly in patients with sarcopenia, to mitigate such risks.

Objectives: Although peroral cholangioscopy has improved the endoscopic treatment of difficult stones, the treatment of intrahepatic stones remains challenging. The incidence of cholangitis is high when peroral cholangioscopy is used to treat intrahepatic stones. This study aimed to investigate the efficacy and safety of endoscopic treatment with peroral cholangioscopy for intrahepatic and common bile duct stones. Methods: Patients aged ≥20 years, who underwent endoscopic treatment with peroral cholangioscopy for intrahepatic or common bile duct stones at Tottori University Hospital from January 2016 to December 2022, were retrospectively evaluated to determine the efficacy and safety of the treatment. Results: Overall, 70 patients were included in this study: 22 in the intrahepatic stone group and 48 in the common bile duct stone group. Stones were smaller (8 vs. 17.5 mm, p < 0.001) and more numerous (p = 0.016) in the intrahepatic stone group than in the common bile duct stone group. Although the common bile duct stone group exhibited a higher rate of complete stone clearance in the first session, no significant differences were observed in the final results. The intrahepatic stone group had a higher incidence of cholangitis (36% vs. 8%, p = 0.007); however, all cases were mild. Conclusions: Endoscopic treatment with peroral cholangioscopy for intrahepatic stones may be associated with a higher incidence of cholangitis than that for common bile duct stones. Since saline irrigation may contribute to the development of cholangitis, it is important to be aware of intraductal bile duct pressure when performing peroral cholangioscopy.