Publications by authors named "Yuji Shimada"

51 Publications

Hepatitis B Surface Antigen Decline During Sofosbuvir and Ribavirin Therapy in Hepatitis B Inactive Carriers Who were co-infected with Hepatitis C.

Intern Med 2021 May 14. Epub 2021 May 14.

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Japan.

Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.
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http://dx.doi.org/10.2169/internalmedicine.7337-21DOI Listing
May 2021

Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis.

Hepatol Res 2021 May 8. Epub 2021 May 8.

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.

Aim: Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis.

Methods: This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation.

Results: Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA-to-tyrosine ratio for 114 patients (72.2%). During a median follow-up period of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis showed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110 µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15-3.11, p = 0.012). Kaplan-Meier analysis showed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p < 0.001).

Conclusions: Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA-to-tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.
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http://dx.doi.org/10.1111/hepr.13651DOI Listing
May 2021

Randomized controlled study on the effects of triple therapy including vonoprazan or rabeprazole for the second-line treatment of infection.

Therap Adv Gastroenterol 2020 11;13:1756284820966247. Epub 2020 Nov 11.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Background And Aim: Inhibition of gastric acid secretion is important for eradicating . Vonoprazan (VPZ) is a strong, long-lasting inhibitor of gastric acid secretion. Studies that examined the effectiveness of VPZ-based triple therapy in second-line treatment have been performed. However, there have been no randomized controlled studies to compare the effect between VPZ-based triple therapy and proton pump inhibitor (PPI)-based triple therapy in second-line treatment, and it is not known which is more effective between VPZ-based and PPI-based therapies. This study aimed to compare the effectiveness of second-line triple therapies including VPZ or rabeprazole (RPZ) as the PPI.

Methods: Eligible patients with infection who failed first-line triple therapy were assigned randomly to the VPZ [VPZ40 mg/day, amoxicillin (AMPC) 1500 mg/day, metronidazole (MNZ) 500 mg/day] or RPZ (RPZ20 mg/day, AMPC1500 mg/day, MNZ500 mg/day) group. A C-urea breath test result of less than 2.5% was considered as successful eradication.

Results: In total, 46 and 41 patients were analyzed as intention to treat (ITT) and per protocol (PP), respectively. Eradication rates in the VPZ and RPZ groups were 73.9% [95% confidence interval (CI) 51.6-89.8%] and 82.6% (95% CI 61.2-95.0%) based on ITT analysis, respectively ( = 0.72). Based on PP analysis, the eradication rates in the VPZ and RPZ groups were 89.5% (95% CI 66.9-98.7%) and 86.4% (95% CI 65.1-97.1%), respectively ( = 1.00). Two patients in the VPZ group and one in the RPZ group discontinued treatment due to side effects ( = 1.00).

Conclusion: There were no significant differences in efficacy and safety between second-line therapies including VPZ or RPZ.
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http://dx.doi.org/10.1177/1756284820966247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675913PMC
November 2020

Association between the severity of constipation and sarcopenia in elderly adults: A single-center university hospital-based, cross-sectional study.

Biomed Rep 2021 Jan 22;14(1). Epub 2020 Oct 22.

Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo 113-8421, Japan.

The aim of the present study was to investigate the association between the severity of constipation and sarcopenia in elderly adults. We conducted a single-center university hospital-based, retrospective cross-sectional study of consecutive outpatients aged ≥65 years from 2017 to 2020. Patients were included in the study if all of the following information were available from medical records: Patient's profile (age, sex, body mass index), laxative/prokinetics use, evaluation of sarcopenia, nutritional status, and questionnaires concerning the severity of constipation [Constipation Scoring System (CSS)], abdominal symptom-related quality of life (QOL) (Izumo scale) and stool shape [Bristol Stool Form Scale (BSFS)]. Multiple regression analysis of risk factors for high CSS score was performed. The results revealed that of the 310 eligible study subjects, [149 men (48.1%) and 161 women (51.9%); mean age, 75.7±6.1 years; mean body mass index, 23.0±3.6 kg/m], sarcopenia was noted in 83 cases (26.8%). The CSS score was significantly higher in the sarcopenia group than that noted in the non-sarcopenia group (4.9±4.9 vs. 3.6±3.6, P=0.009). The CSS score was significantly associated with the albumin level (r=-0.148), lymphocyte count (r=-0.118), CONUT score (r=0.130), reflux-related QOL score (r=0.155), upper abdominal pain-related QOL score (r=0.171), fullness-related QOL score (r=0.299), constipation-related QOL score (r=0.615), diarrhea-related QOL score (r=0.235) and BSFS score (r=-0.114). In multiple regression analysis, independent predictors for CSS score were sarcopenia [standardized partial regression coefficient (β)=0.107, P=0.032], constipation-related QOL score (β=0.537, P<0.001), laxative/prokinetics use (β=0.211, P<0.001) and BSFS score (β=-0.098, P=0.031) (R=0.436). In conclusion, sarcopenia, constipation-related QOL score, laxative/prokinetics use and BSFS score are associated with the severity of constipation in elderly adults.
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http://dx.doi.org/10.3892/br.2020.1378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678610PMC
January 2021

Linked color imaging improves visibility of reflux esophagitis.

BMC Gastroenterol 2020 Oct 27;20(1):356. Epub 2020 Oct 27.

Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: With more prevalent gastroesophageal reflux disease comes increased cases of Barrett's esophagus and esophageal adenocarcinoma. Image-enhanced endoscopy using linked-color imaging (LCI) differentiates between mucosal colors. We compared LCI, white light imaging (WLI), and blue LASER imaging (BLI) in diagnosing reflux esophagitis (RE).

Methods: Consecutive RE patients (modified Los Angeles [LA] classification system) who underwent esophagogastroduodenoscopy using WLI, LCI, and BLI between April 2017 and March 2019 were selected retrospectively. Ten endoscopists compared WLI with LCI or BLI using 142 images from 142 patients. Visibility changes were scored by endoscopists as follows: 5, improved; 4, somewhat improved; 3, equivalent; 2, somewhat decreased; and 1, decreased. For total scores, 40 points was considered improved visibility, 21-39 points was comparable to white light, and < 20 points equaled decreased visibility. Inter- and intra-rater reliabilities (Intra-class Correlation Coefficient [ICC]) were also evaluated. Images showing color differences (ΔE*) and L* a* b* color values in RE and adjacent esophageal mucosae were assessed using CIELAB, a color space system.

Results: The mean age of patients was 67.1 years (range: 27-89; 63 males, 79 females). RE LA grades observed included 52 M, 52 A, 24 B, 11 C, and 3 D. Compared with WLI, all RE cases showed improved visibility: 28.2% (40/142), LA grade M: 19.2% (10/52), LA grade A: 34.6% (18/52), LA grade B: 37.5% (9/24), LA grade C: 27.3% (3/11), and LA grade D: 0% (0/3) in LCI, and for all RE cases: 0% in BLI. LCI was not associated with decreased visibility. The LCI inter-rater reliability was "moderate" for LA grade M and "substantial" for erosive RE. The LCI intra-rater reliability was "moderate-substantial" for trainees and experts. Color differences were WLI: 12.3, LCI: 22.7 in LA grade M; and WLI: 18.2, LCI: 31.9 in erosive RE (P < 0.001 for WLI vs. LCI).

Conclusion: LCI versus WLI and BLI led to improved visibility for RE after subjective and objective evaluations. Visibility and the ICC for minimal change esophagitis were lower than for erosive RE for LCI. With LCI, RE images contrasting better with the surrounding esophageal mucosa were more clearly viewed.
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http://dx.doi.org/10.1186/s12876-020-01511-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590454PMC
October 2020

Mucinous Cystadenocarcinoma of the Pancreas with Cyst Infection in a Male Patient.

Intern Med 2020 1;59(19):2383-2389. Epub 2020 Oct 1.

Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Japan.

Follow-up computed tomography revealed a 40-mm pancreatic tail cyst in a 59-year-old man with type 1 diabetes mellitus. An intraductal papillary mucinous neoplasm was suspected; mucinous cystic neoplasm (MCN) was not considered because the patient was a man. During follow-up, cyst infection occurred but was improved by conservative treatment. At the 24-month follow up examination, cyst nodules had developed, corresponding to an increase in the carbohydrate antigen 19-9 level. Mucinous cystadenocarcinoma (MCC) was diagnosed pathologically based on distal pancreatectomy. A diagnosis of male MCN/MCC is often delayed, which may lead to a poor prognosis. MCN infection is also rare and poorly recognized. We observed an atypical male case of MCN/MCC.
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http://dx.doi.org/10.2169/internalmedicine.4937-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644490PMC
November 2020

Eosinophilic Gastroenteritis in an Ulcerative Colitis Patient During Treatment with Tumor Necrosis Factor-alpha Antagonist.

Intern Med 2020 15;59(16):1977-1981. Epub 2020 Aug 15.

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Japan.

A 45-year-old man with steroid-dependent ulcerative pancolitis was hospitalized with frequent diarrhea, abdominal pain and distension 3 months after induction of golimumab, a tumor necrosis factor-alpha antagonist. Computed tomography showed wall thickening from the stomach to the colon and massive ascites. Peripheral blood test revealed eosinophilia. A large number of eosinophils were observed in the ascites fluid. Although esophagogastroduodenoscopy showed no abnormal findings and colonoscopy showed ulcerative colitis with a Mayo endoscopic subscore of 1, eosinophil infiltration was histologically observed. Based on these findings, we diagnosed him with eosinophilic gastroenteritis and started prednisolone. Consequently, his eosinophil counts and abdominal symptoms dramatically improved.
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http://dx.doi.org/10.2169/internalmedicine.4554-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492116PMC
January 2021

The Association between Frailty and Abdominal Symptoms: A Hospital-based Cross-sectional Study.

Intern Med 2020 15;59(14):1677-1685. Epub 2020 Jul 15.

Department of Gastroenterology, University of Juntendo, School of Medicine, Japan.

Objective The association between frailty and abdominal symptoms has not been evaluated. Methods We conducted a hospital-based, retrospective cross-sectional study of consecutive outpatients ≥65 years old at the Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center from 2017 to 2019. Patients were included in the study if all of the following information was available from their medical records: patient's profile, the evaluation of osteoporosis, sarcopenia, frailty, nutritional status, findings of upper gastrointestinal endoscopy, and questionnaire results for abdominal symptoms [Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Constipation Scoring System (CSS)]. We divided the subjects into frailty and non-frailty groups and investigated the risk factors for frailty. Results Of the 313 eligible study subjects [134 men (42.8%) and 179 women (57.2%); mean age, 75.7±6.0 years; mean body mass index, 22.8±3.6 kg/m], frailty was noted in 71 cases (22.7%). In a univariate analysis, an older age (p<0.001), female gender (p=0.010), successful eradication of Helicobacter pylori (p=0.049), proton pump inhibitor (PPI) use (p<0.001), laxative/prokinetics use (p=0.008), sarcopenia (p<0.001), osteoporosis (p<0.001), hypozincemia (p=0.002), hypoalbuminemia (p<0.001), low lymphocytes (p=0.004), a high CONUT score (p<0.001), a high FSSG score (p=0.001), and a high CSS score (p<0.001) were significantly associated with frailty. A multivariate logistic regression analysis showed that an older age [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.08-1.24, p<0.001], PPI use (OR 2.42; 95% CI 1.18-4.98, p=0.016), sarcopenia (OR 7.35; 95% CI 3.30-16.40, p<0.001), hypozincemia (OR 0.96; 95% CI 0.92-0.99, p=0.027), a high FSSG score (OR 1.08; 95% CI 1.01-1.16, p=0.021), and a high CSS score (OR 1.13; 95% CI 1.03-1.23, p=0.007) were significantly associated with frailty. Conclusion Advanced age, PPI user, sarcopenia, hypozincemia, a high FSSG score, and high CSS score are associated with frailty.
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http://dx.doi.org/10.2169/internalmedicine.4399-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434549PMC
September 2020

Successful Management of Hemosuccus Pancreaticus due to Pancreatic Adenocarcinoma by Chemoradiotherapy.

Intern Med 2020 Sep 2;59(17):2135-2141. Epub 2020 Jun 2.

Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Japan.

Management of hemosuccus pancreaticus (HP) due to pancreatic adenocarcinoma is problematic. This is the first report of the successful management of HP caused by pancreatic adenocarcinoma by chemoradiotherapy, which is a treatment option for cases with a high surgical risk that are not suitable for interventional radiology. In the present case, bloody pancreatic juice was detected in the main pancreatic duct, and anemia worsened without repeated blood transfusions. The patient ultimately underwent chemoradiotherapy comprising radiation of 3 Gy in 15 fractions concomitant with systemic chemotherapy of S-1. After the treatments, the anemia improved, and the patient was discharged on day 45.
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http://dx.doi.org/10.2169/internalmedicine.4372-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516308PMC
September 2020

On-treatment Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Level and Risk of Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogue Therapy.

Int J Mol Sci 2020 Mar 17;21(6). Epub 2020 Mar 17.

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.

We aimed to analyze the serum level of a novel fibrosis marker, Mac-2-binding protein glycosylation isomer (M2BPGi), and its predictive value for hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) under nucleot(s)ide analogue (NA) therapy. Serum M2BPGi levels were quantified in 147 CHB patients at baseline, 48 weeks after starting NA therapy, and at the patients' last visit. The serum M2BPGi level serially decreased at each time point. During the median follow-up time of 6.6 years, 14 of 147 patients developed HCC. Multivariate Cox proportional hazard analysis demonstrated that high serum M2BPGi at 48 weeks was an independent risk factor for HCC development. A cutoff value of M2BPGi at 48 weeks > 1.5 showed an adjusted hazard ratio = 34.9 (95% confidence interval, 4.3-284.9). The 3- and 5-year cumulative incidence of HCC in patients with low M2BPGi were 0.9% and 4.2%, respectively, whereas those in patients with high M2BPGi were 10.1% and 25.6%, respectively ( < 0.001). In conclusion, Serum M2BPGi level at 48 weeks is a useful predictor for HCC development in patients with CHB who receive NA therapy.
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http://dx.doi.org/10.3390/ijms21062051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139452PMC
March 2020

Elevated serum procalcitonin levels and their association with the prognosis of patients with liver cirrhosis.

Eur J Gastroenterol Hepatol 2020 09;32(9):1222-1228

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital.

Objectives: Bacterial infection is a major complication in patients with liver cirrhosis. Procalcitonin is an early diagnostic marker of bacterial infection. This study aimed to investigate the association between the serum procalcitonin levels and the prognosis of patients with liver cirrhosis.

Methods: We retrospectively analyzed the serum procalcitonin levels in 236 hospitalized patients with liver cirrhosis. The impact of the serum procalcitonin level on their prognoses was evaluated using multivariate Cox proportional hazards analyses and the Kaplan-Meier method.

Results: The serum procalcitonin level was higher (≥0.05 ng/mL) in 151 (64%) patients, and it was significantly higher in the patients with Child-Turcotte-Pugh class C than in those with Child-Turcotte-Pugh classes A/B. Patients with refractory ascites, hepatic encephalopathy, gastrointestinal bleeding, and bacterial infections had elevated serum procalcitonin levels. The multivariate analyses showed a serum procalcitonin level ≥0.05 ng/mL was an independent prognostic factor for liver cirrhosis (hazard ratio = 1.64; 95% confidence interval = 1.07-2.53; P = 0.024). During a median follow-up interval of 2.1 years, the three-year cumulative survival rates for the patients with normal and elevated serum procalcitonin levels were 72.9 and 56.0%, respectively (P < 0.001). The subgroup analyses that stratified the patients according to age, the Child-Turcotte-Pugh classification, and the presence of liver cancer showed the serum procalcitonin level was significantly associated with their prognoses.

Conclusions: The patients with liver cirrhosis had higher serum procalcitonin levels, regardless of local bacterial infections, and higher procalcitonin levels were associated with poor prognoses.
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http://dx.doi.org/10.1097/MEG.0000000000001644DOI Listing
September 2020

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy.

Hepatol Res 2020 Feb 5;50(2):214-223. Epub 2020 Jan 5.

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.

Aim: Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis.

Methods: A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids and tyrosine, and branched-chain amino acid-to-tyrosine ratio were determined. The hazard ratios of factors associated with liver-related events were analyzed by Cox proportional hazard analysis.

Results: Of the 75 patients enrolled, 12 showed a decrease in serum branched-chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched-chain amino acid-to-tyrosine ratio decreased in 16 patients. During a median 5.6-year follow up, liver-related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 μmol/L was identified as a cut-off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3-101.5, P < 0.001). Kaplan-Meier analysis showed that the 5-year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10-year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001).

Conclusion: Elevation of serum tyrosine concentration indicates a high risk of liver-related events in primary biliary cholangitis patients receiving urusodeoxycholic acid therapy.
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http://dx.doi.org/10.1111/hepr.13434DOI Listing
February 2020

Current status of first- and second-line eradication therapy in the metropolitan area: a multicenter study with a large number of patients.

Therap Adv Gastroenterol 2019 4;12:1756284819858511. Epub 2019 Jul 4.

Tokyo Hp Study Group, Tokyo, Japan.

Background: The environment surrounding eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan's demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of in the metropolitan area and examined factors concerning successful eradication.

Methods: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed.

Results: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies.

Conclusion: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.
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http://dx.doi.org/10.1177/1756284819858511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611030PMC
July 2019

Linked Color Imaging and the Kyoto Classification of Gastritis: Evaluation of Visibility and Inter-Rater Reliability.

Digestion 2020 12;101(5):598-607. Epub 2019 Jul 12.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Background/aims: To compare white light imaging (WLI) with linked color imaging (LCI) and blue LASER imaging (BLI) in endoscopic findings of Helicobacter pylori presently infected, previously infected, and uninfected gastric mucosae for visibility and inter-rater reliability.

Methods: WLI, LCI and BLI bright mode (BLI-bright) were used to obtain 1,092 endoscopic images from 261 patients according to the Kyoto Classification of Gastritis. Images were evaluated retrospectively by 10 experts and 10 trainee endoscopists and included diffuse redness, spotty redness, map-like redness, patchy redness, red streaks, intestinal metaplasia, and an atrophic border (52 cases for each finding, respectively). Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Visibility was assessed from totaled scores. The inter-rater reliability (intraclass correlation coefficient) was also evaluated.

Results: Compared with WLI, all endoscopists reported improved visibility with LCI: 55.8% for diffuse redness; LCI: 38.5% for spotty redness; LCI: 57.7% for map-like redness; LCI: 40.4% for patchy redness; LCI: 53.8% for red streaks; LCI: 42.3% and BLI-bright: 80.8% for intestinal metaplasia; LCI: 46.2% for an atrophic border. For all endoscopists, the inter-rater reliabilities of LCI compared to WLI were 0.73-0.87.

Conclusion: The visibility of each endoscopic finding was improved by LCI while that of intestinal metaplasia was improved by BLI-bright.
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http://dx.doi.org/10.1159/000501534DOI Listing
July 2019

A case of primary biliary cholangitis overlapping with type 2 autoimmune hepatitis.

Clin J Gastroenterol 2020 Feb 8;13(1):79-82. Epub 2019 Jul 8.

Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan.

A 42-year-old woman was admitted to our hospital with cholestatic liver injury. Serological examination revealed anti-mitochondrial M2 antibody positivity and anti-nuclear antibody and anti-smooth muscle antibody negativity. Histological examination of the first liver biopsy revealed chronic nonsuppurative destructive cholangitis with epithelioid granulomas. Ursodeoxycholic acid therapy successfully treated her cholestasis. Sixteen months later, she developed acute icteric hepatitis with elevation of serum aspartate and alanine aminotransferase levels. Anti-mitochondrial M2 positivity and anti-nuclear antibody and anti-smooth muscle antibody negativity persisted at that time. However, it became clear that anti-liver kidney microsomal type 1 antibody was positive. Histological examination of the second liver biopsy demonstrated scarce interface hepatitis and evident parenchymal inflammation and centrilobular zonal necrosis. Her liver biochemical test results promptly improved with the addition of prednisolone therapy. Considering the findings, she was diagnosed with primary biliary cholangitis-type 2 autoimmune hepatitis overlap syndrome. According to a literature review, this is an extremely rare autoimmune overlap syndrome.
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http://dx.doi.org/10.1007/s12328-019-01017-2DOI Listing
February 2020

Evaluation of symptomatic reflux esophagitis in proton pump inhibitor users.

Biomed Rep 2019 May 9;10(5):277-282. Epub 2019 Apr 9.

Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo 113-8421, Japan.

The aim of the present study was to evaluate symptomatic reflux esophagitis (RE) in proton pump inhibitor (PPI) users. The present study conducted a hospital-based, retrospective cross-sectional study of consecutive RE cases in PPI users at Juntendo University Hospital recruited between 2008 and 2016. Eligible patients were PPI users with a complete patient profile, who completed the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) questionnaire, and who underwent upper gastrointestinal endoscopy for the examination of RE, hiatal hernia (HH) and endoscopic gastric mucosal atrophy (EGA). The patients with RE who were administered PPIs were divided into two groups: Those with symptomatic RE (FSSG≥8) and those with non-symptomatic RE (FSSG<8). The present study investigated the risk factors for symptomatic RE among the patients with RE patients who were administered PPIs. Of the 13,052 cases who underwent patient profiling, the FSSG questionnaire and upper gastrointestinal endoscopy, a total of 2,444 PPI users were eligible. Of the PPI users, 206 cases (8.4%) had RE. Among the 206 patients with RE, 115 (55.8%) had symptomatic RE. The profile of the symptomatic and non-symptomatic RE groups were as follows: A total of 45 females (39.1%) vs. 32 females (35.2%; non-significant); mean ± standard deviation age, 54.8±13.5 vs. 62.9±11.1 years (P<0.01); mean body mass index, 23.5±3.3 vs. 23.2±3.8 (non-significant); severe RE, 12 (10.4%) vs. 2 (2.2%; P<0.05); HH, 70 (60.9%) vs. 40 (44.0%; P<0.05); and mean score of EGA, 1.2±1.8 vs. 1.8±2.1 (P<0.05). Multivariate analysis revealed that a younger age [odds ratio (OR)=0.94; 95% confidence interval (CI): 0.92-0.97, P<0.01] and HH(+) (OR=2.37; 95% CI: 1.30-4.34, P<0.01) were associated with symptomatic RE among patients with RE who were administered PPIs. In conclusion, a younger age and HH were associated with symptomatic RE in patients with RE who were administered PPIs.
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http://dx.doi.org/10.3892/br.2019.1206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489533PMC
May 2019

Effect of Esophageal Endoscopic Submucosal Dissection on Motility and Symptoms: A Prospective Study.

Gastroenterol Res Pract 2018 3;2018:3735473. Epub 2018 Jun 3.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Background: Endoscopic submucosal dissection (ESD) of esophageal tumors can cause stenosis, yet the effect of esophageal ESD on motility remains unclarified. This study aimed to compare esophageal motility and symptoms, before and after ESD, using high-resolution manometry (HRM) and symptom scoring.

Methods: Twenty-eight patients with 35 cT1a cancers were prospectively enrolled between December 2014 and February 2016. Pre- and post-ESD symptom score and HRM were recorded. Based on circumferential resection (CR), patients were divided into group A ( = 17, <2/3 CR) or B ( = 11, 2/3 CR or greater). HRM parameters evaluated were distal contractile integral (DCI), contractile front velocity (CFV), intrabolus pressure, integrated relaxation pressure, distal latency, and peristaltic breaks.

Results: Symptom scores worsened after ESD in 8/11 patients in group B, and 0/17 patients in group A. There was no significant difference in any HRM parameter after ESD in the whole study group but mean DCI tended to increase ( = 0.07). In group B, DCI increased significantly after ESD ( = 0.04), and CFV tended to decrease after ESD ( = 0.08).

Conclusions: DCI tended to increase after esophageal ESD. ESD affected the symptom score and esophageal motility in cases with 2/3 CR or greater. This trial is registered with UMIN000015829.
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http://dx.doi.org/10.1155/2018/3735473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008697PMC
June 2018

A case of ischemic gastroduodenal disease in a patient who was receiving hemodialysis treatment that was managed by conservative treatment.

Clin J Gastroenterol 2018 Oct 8;11(5):386-390. Epub 2018 May 8.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

A 69-year-old man was under maintenance dialysis due to diabetic renal failure. He had a drop in blood pressure during dialysis, developed hematemesis, and was transported to our hospital. Emergency upper gastrointestinal endoscopy revealed diffuse erosion, mucosal sloughing, and edematous mucosa in the upper body of the stomach to the posterior wall of the antrum and to the greater curvature, which were considered to be an ischemic change. His underlying diseases included diabetic renal failure, chronic arteriosclerosis obliterans, cerebral infarction, internal carotid artery stenosis, hypertension, and myocardial infarction. Blood evaluation showed only mild inflammation and no fibrinolytic hyperactivity. Contrast-enhanced computed tomography (CECT) showed no occlusion of blood vessels. It was considered that the patient had a transient ischemic change due to blood pressure drop. The patient's condition improved with conservative treatment.
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http://dx.doi.org/10.1007/s12328-018-0865-1DOI Listing
October 2018

Improved Visibility of Barrett's Esophagus with Linked Color Imaging: Inter- and Intra-Rater Reliability and Quantitative Analysis.

Digestion 2018 10;97(2):183-194. Epub 2018 Jan 10.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Background/aims: To evaluate the usefulness of linked color imaging (LCI) and blue LASER imaging (BLI) in Barrett's esophagus (BE) compared with white light imaging (WLI).

Methods: Five expert and trainee endoscopists compared WLI, LCI, and BLI images obtained from 63 patients with short-segment BE. Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and one (decreased). Scores were evaluated to assess visibility. The inter- and intra-rater reliability (intra-class correlation coefficient) of image assessments were also evaluated. Images were objectively evaluated based on L* a* b* color values and color differences (ΔE*) in a CIELAB color space system.

Results: Improved visibility compared with WLI was achieved for LCI: 44.4%, BLI: 0% for all endoscopists; LCI: 55.6%, BLI: 1.6% for trainees; and LCI: 47.6%, BLI: 0% for experts. The visibility score of trainees compared with experts was significantly higher for LCI (p = 0.02). Intra- and inter-rater reliability ratings for LCI compared with WLI were "moderate" for trainees, and "moderate-substantial" for experts. The ΔE* revealed statistically significant differences between WLI and LCI.

Conclusion: LCI improved the visibility of short-segment BE compared with WLI, especially for trainees, when evaluated both subjectively and objectively.
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http://dx.doi.org/10.1159/000485459DOI Listing
August 2018

A Systematic Review of the Effectiveness of Antianxiety and Antidepressive Agents for Functional Dyspepsia.

Intern Med 2017 Dec 11;56(23):3127-3133. Epub 2017 Oct 11.

Department of Gastroenterology, Juntendo University School of Medicine, Japan.

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.
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http://dx.doi.org/10.2169/internalmedicine.9099-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742382PMC
December 2017

A Randomized, Double-Blind, Pilot Study of the Effect of Famotidine on Acotiamide Treatment for Functional Dyspepsia.

Digestion 2017 13;96(1):5-12. Epub 2017 Jun 13.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Background/aims: Acotiamide, a prokinetic drug, is used to treat functional dyspepsia (FD), especially postprandial distress syndrome (PDS). However, a treatment for FD patients with PDS and/or epigastric pain syndrome (EPS) has not been established. We investigated the efficacy of famotidine in combination with acotiamide for FD.

Methods: Fifty blindly randomized FD patients received placebo with acotiamide, or famotidine with acotiamide, for 4 weeks. Treatment efficacy was assessed by overall treatment effects (OTE), total, PDS and EPS symptom scores, and impairment of quality of life (QOL).

Results: After OTE assessment, patients who felt affected by treatment comprised 40.9 and 57.9% of famotidine and placebo groups, respectively, after 4 weeks' treatment, with no significant difference between groups. A significant decrease was seen in total, PDS, and EPS symptom scores, and in QOL impairment, after 4 weeks' treatment compared with pretreatment scores for famotidine and placebo groups, but was not observed between groups. The proportion of patients showing a ≥50% decrease in EPS symptom scores was greater in the famotidine than that in the placebo group for every observation point, with the greatest difference observed after 2 weeks' treatment.

Conclusion: The effectiveness of famotidine and acotiamide combination therapy in FD was similar to the effectiveness of acotiamide therapy alone.
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http://dx.doi.org/10.1159/000477345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637310PMC
April 2018

Efficacy of a potassium-competitive acid blocker for improving symptoms in patients with reflux esophagitis, non-erosive reflux disease, and functional dyspepsia.

Biomed Rep 2017 Feb 15;6(2):175-180. Epub 2016 Dec 15.

Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo 113-8421, Japan.

The aim of the present study was to investigate the efficacy of a potassium-competitive acid blocker (PCAB) named vonoprazan (VPZ) for improving symptoms in patients with reflux esophagitis (RE), non-erosive reflux disease (NERD), and functional dyspepsia (FD). A hospital-based, retrospective study of outpatients in our department (Department of Gastroenterology, University of Juntendo, Tokyo, Japan) between March 2015 and August 2016 was performed. The patients who were experiencing heartburn, acid regurgitation, gastric pain, and/or a heavy feeling in the stomach of at least moderate severity at baseline were treated with 20 mg VPZ once daily for 4 weeks. The patients completed the global overall symptom (GOS) scale to determine their symptom severity at baseline and after the 4 week treatment period. The proportions of patients with RE, NERD, and FD achieving improvement of their symptoms, defined as a GOS scale score of 1 ('no problem') or 2 ('minimal problem'), were evaluated. During 4 weeks of VPZ therapy, changes in the gastroesophageal reflux disease (GERD) score, which was defined as the total points for heartburn and acid regurgitation on the GOS scale in patients with RE and NERD, and in the FD score, which was defined as the total points for gastric pain and a heavy feeling in the stomach on the GOS scale in patients with FD, were also evaluated. A total of 88 eligible cases were included in the present study, comprising 20 patients with RE, 25 patients with NERD, and 43 patients with FD. The rates of symptomatic improvement in patients with RE, NERD, and FD were 75.0, 60.0, and 48.8%, respectively. For the patients who were first administered VPZ, the rates of symptomatic improvement were 90.9, 66.7, and 58.8% in patients with RE, NERD, and FD, respectively. For those patients who were resistant to 8 weeks of proton pump inhibitor therapy, the rates of symptomatic improvement were 55.6, 53.8, and 42.3% in patients with RE, NERD, and FD, respectively. The GERD score in patients with RE and NERD, and the FD score in FD patients, were decreased after 4 weeks of VPZ therapy (P<0.01). In patients with RE, NERD and FD, the possibility that PCAB may be used as a novel therapeutic drug was suggested. However, the number of study subjects was small; therefore, further, larger and prospective studies are required.
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http://dx.doi.org/10.3892/br.2016.828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351306PMC
February 2017

Prediction of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication Using Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein.

Int J Mol Sci 2016 Dec 20;17(12). Epub 2016 Dec 20.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo 113-8431, Japan.

We aimed to clarify the association between a novel serum fibrosis marker, agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA⁺-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA⁺-M2BP (≥2.80 cut off index (COI), HR = 15.20, = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA⁺-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA⁺-M2BP were 7.7% and 17.6%, respectively ( < 0.001). In addition, combination of serum WFA⁺-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively ( < 0.001). In conclusion, pretreatment serum WFA⁺-M2BP level is a useful predictor for HCC development after achieving SVR.
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http://dx.doi.org/10.3390/ijms17122143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187943PMC
December 2016

Association of medications for lifestyle-related diseases with reflux esophagitis.

Ther Clin Risk Manag 2016 4;12:1507-1515. Epub 2016 Oct 4.

Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo.

Background: Because of a change in lifestyle, especially adoption of westernized eating habits, lifestyle-related diseases have become increasingly prevalent. The aim of this study was to investigate the association of medications for lifestyle-related diseases with reflux esophagitis (RE).

Methods: We conducted a hospital-based, cross-sectional retrospective study of consecutive outpatients who received an upper gastrointestinal endoscopy in our department from February 2008 to November 2014, which was performed by one specialist who was a member of the Japan Gastroenterological Endoscopy Society. We investigated the patient profile, () infection status, medications for lifestyle-related diseases (including calcium channel blockers, statins, and bisphosphonates), and upper gastrointestinal endoscopic findings (RE, hiatal hernia, Barrett's mucosa, and endoscopic gastric mucosal atrophy [EGA]). Patients with gastrectomy, peptic ulcer disease, gastric or esophageal malignant disease, and those who used proton pump inhibitors or histamine-2 receptor antagonists were excluded. We divided the subjects into a group without RE (RE(-)) and a RE (RE(+)) group as judged by endoscopy, and investigated the risk factors for RE.

Results: Of 1,744 consecutive cases, 590 cases (300 males and 290 females; mean age 60.5±13.2 years) were eligible. RE(-) and RE(+) cases numbered 507 and 83, respectively. Bivariate analysis showed significant positive associations of RE with male sex, body mass index (BMI), calcium channel blockers, Barrett's mucosa, hiatal hernia and negative associations of RE with positivity, EGA. Multivariate analysis showed significant positive associations of RE with BMI (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.10-1.29), use of calcium channel blockers (OR: 2.12, 95% CI: 1.16-3.87), Barrett's mucosa (OR: 2.97, 95% CI: 01.64-5.38), hiatal hernia (OR: 3.13, 95% CI: 1.79-5.47) and negative associations of RE with positivity (OR: 0.20, 95% CI: 0.07-0.57), use of statins (OR: 0.42, 95% CI: 0.18-0.96), and EGA (OR: 0.83, 95% CI: 0.70-0.98).

Conclusion: Calcium channel blockers were positively associated with RE and statins were negatively associated with RE, while bisphosphonates were not associated with RE.
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http://dx.doi.org/10.2147/TCRM.S114709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063121PMC
October 2016

Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication.

World J Gastroenterol 2016 Sep;22(33):7569-78

Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.

Aim: To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.

Methods: In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test.

Results: Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (≥ 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression.

Conclusion: Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.
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http://dx.doi.org/10.3748/wjg.v22.i33.7569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011670PMC
September 2016

Efficacy of alfacalcidol and alendronate on lumbar bone mineral density in osteoporotic patients using proton pump inhibitors.

Biomed Rep 2016 Aug 30;5(2):165-170. Epub 2016 Jun 30.

Department of Gastroenterology, School of Medicine, University of Juntendo, Tokyo 113-8421, Japan.

It has been indicated that proton pump inhibitor (PPI) use is associated with a loss of the anti-fracture efficacy of alendronate (AD). However, there are few prospective studies that have investigated the efficacy of AD on lumbar bone mineral density (BMD) in osteoporotic patients who are using PPIs. Thus, the aim of the present study was to investigate the efficacy of alfacalcidol (AC) and AD on lumbar BMD in osteoporotic patients using PPIs. A prospective, randomized, active control study enrolled such osteoporotic patients (age, ≥50 years). The patients were randomly assigned to receive AC (1 µg/day) or AD (35 mg/week) and were followed up for one year. Patient profiles were maintained, and lumbar BMD, bone-specific alkaline-phosphatase (BAP) and collagen type-I cross-linked N-telopeptide (NTX), upper gastrointestinal endoscopy results, and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) were evaluated. Percentage changes in lumbar BMD, NTX, BAP, and change in FSSG score from baseline to the end of one year of treatment were investigated. Sixteen patients were eligible for analysis (eight assigned to receive AC, eight assigned to receive AD). The percentage change in lumbar BMD from baseline to the end of treatment was -0.4±4.0% for the AC group vs. 6.8±6.3% for the AD group (P=0.015). No significant percentage change of BAP and NTX between the two groups was observed. Subsequent to one year of treatment, the FSSG score did not change from the baseline values for either study group, and no new bone fractures or esophagitis were observed in either group of patients. The findings demonstrated that in osteoporotic patients using concomitant PPIs, there was a greater increase in lumbar BMD after one year of treatment with AD compared with AC. However, the number of study subjects was small; thus, further, large prospective studies are required to determine the effect of AD in osteoporotic patients using concomitant PPIs.
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http://dx.doi.org/10.3892/br.2016.710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950806PMC
August 2016

Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients.

PLoS One 2016 29;11(6):e0157835. Epub 2016 Jun 29.

Department of Hematology, Shinshu University School of Medicine, Matsumoto, Japan.

The activated partial thromboplastin time (APTT) assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg) might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003). Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157835PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927146PMC
July 2017

Aldo-keto reductase family 1 member B10 is associated with hepatitis B virus-related hepatocellular carcinoma risk.

Hepatol Res 2017 Mar 11;47(3):E85-E93. Epub 2016 May 11.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Aim: Recent reports have indicated that aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)-infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection.

Methods: Expression of AKR1B10 in the liver of 119 chronic HBV-infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan-Meier analysis.

Results: Expression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow-up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0-38.6; P < 0.001). The 5-year cumulative incidences of HCC were 20.6% and 2.6% in patients with high and low AKR1B10 expression, respectively (P < 0.001). Patients with high AKR1B10 expression had significantly higher alanine aminotransferase levels during follow-up than those with low expression, even though antiviral treatment decreased HBV-DNA levels in both groups.

Conclusion: Chronic HBV-infected patients with high hepatic AKR1B10 expression had an increased risk of HCC development. This suggests that AKR1B10 upregulation might play a role in the early stages of HBV-related hepatocarcinogenesis.
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http://dx.doi.org/10.1111/hepr.12725DOI Listing
March 2017

Optimization of Deep Sedation with Spontaneous Respiration for Therapeutic Endoscopy Combining Propofol and Bispectral Index Monitoring.

Gastroenterol Res Pract 2015 13;2015:282149. Epub 2015 Aug 13.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.

Background/Aims. This study aimed to establish optimal propofol anesthesia for therapeutic endoscopy, which has not been established. Methodology. We retrospectively investigated data on 89 patients who underwent upper-GI endoscopic submucosal dissection or endoscopic mucosal resection under anesthesia with propofol. Examined doses of propofol were changed according to efficacy and/or adverse events and classified into 5 periods. A bispectral index (BIS) monitor was used at Period 5 to decrease the incidence of adverse events caused by oversedation. The initial dose of propofol was administered after bolus injection of pethidine hydrochloride (0.5 mg/kg), and 1.0 mL of propofol was added every minute until the patients fell asleep. Continuous and bolus infusion were performed to maintain sedation. When the patient moved or an adverse event occurred, the maintenance dose examined was increased or decreased by 5 mL/h regardless of body weight. Results. Dose combinations (introduction : maintenance) and patient numbers for each period were as follows: Period 1 (n = 27), 0.5 mg/kg : 5 mg/kg/h; Period 2 (n = 11), 0.33 mg/kg : 3.3 mg/kg/h; Period 3 (n = 7), 0.5 mg/kg : 3.3 mg/kg/h; Period 4 (n = 14), 0.5 mg/kg : 2.5 mg/kg/h; Period 5 (n = 30), 0.5 mg/kg : 2.5 mg/kg/h, using BIS monitor. During Period 5, an adverse event occurred in 10.0% of patients, which was lower than that for Periods 1-4. Conclusions. Period 5 propofol anesthesia with BIS protocol could be safe and useful for therapeutic endoscopy under deep sedation with spontaneous respiration.
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http://dx.doi.org/10.1155/2015/282149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550768PMC
September 2015

Risk factors for osteoporosis in Japan: is it associated with Helicobacter pylori?

Ther Clin Risk Manag 2015 6;11:381-91. Epub 2015 Mar 6.

Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, Japan.

Background: A number of diseases and drugs may influence bone mineral density; however, there are few reports concerning the relationship between lifestyle-related diseases and osteoporosis in Japan as determined by multivariate analysis. The aim of this study was to investigate the risk factors for osteoporosis and whether infection by or eradication of Helicobacter pylori is associated with osteoporosis.

Methods: Between February 2008 and November 2014, using a cross-sectional study design, we investigated patient profile (age, sex, BMI, alcohol, smoking), H. pylori infection status, comorbidities, internal medicine therapeutic agents (calcium channel blocker, HMG-CoA reductase inhibitors, proton pump inhibitor), serum parameters (Hb, calcium, γGTP), bone turn over markers (bone-specific alkaline phosphatase (BAP) and collagen type I cross-linked N telopeptide (NTX), findings on dual-energy x-ray absorptiometry (DEXA) and upper gastrointestinal endoscopy, and Frequency Scale for the Symptoms of GERD score in consecutive outpatients aged ≥50 years at our hospital. We divided the subjects into an osteoporosis group and a non-osteoporosis group and investigated risk factors for osteoporosis between the two groups by bivariate and multivariate analyses.

Results: Of the 255 eligible study subjects, 43 (16.9%) had osteoporosis. Bivariate analysis showed that advanced age, female sex, lower body mass index, lower cumulative alcohol intake, lower Brinkman index, H. pylori positivity, lower hemoglobin, bone-specific alkaline phosphatase, lower prevalence of hiatal hernia, and endoscopic gastric mucosal atrophy were related to osteoporosis. Multivariate analysis showed that advanced age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.07-1.19, P<0.001), female sex (OR 6.27, 95% CI 2.26-17.39, P<0.001), low BMI (OR 0.82, 95% CI 0.72-0.94, P=0.005), H. pylori positivity (OR 3.00, 95% CI 1.31-6.88, P=0.009), and BAP (OR 1.07, 95% CI 1.01-1.14, P=0.035) were related to osteoporosis.

Conclusion: Advanced age, low BMI, BAP, and H. pylori positivity were risk factors for osteoporosis; however, the success of H. pylori eradication was not a risk factor for osteoporosis in Japan.
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http://dx.doi.org/10.2147/TCRM.S80647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358368PMC
April 2015