Publications by authors named "Kazuhiko Koike"

1,045 Publications

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Enlarged folds on endoscopic gastritis as a predictor for submucosal invasion of gastric cancers.

World J Gastrointest Endosc 2021 Sep;13(9):426-436

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku 113-8655, Tokyo, Japan.

Background: Accurate diagnosis of the depth of gastric cancer invasion is crucial in clinical practice. The diagnosis of gastric cancer depth is often made using endoscopic characteristics of the tumor and its margins; however, evaluating invasion depth based on endoscopic background gastritis remains unclear.

Aim: To investigate predicting submucosal invasion using the endoscopy-based Kyoto classification of gastritis.

Methods: Patients with gastric cancer detected on esophagogastroduodenoscopy at Toyoshima Endoscopy Clinic were enrolled. We analyzed the effects of patient and tumor characteristics, including age, sex, body mass index, surveillance endoscopy within 2 years, current infection, the Kyoto classification, and Lauren's tumor type, on submucosal tumor invasion and curative endoscopic resection. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. Atrophy was characterized by non-reddish and low mucosa. Intestinal metaplasia was detected as patchy whitish or grayish-white flat elevations, forming an irregular uneven surface. An enlarged fold referred to a fold width ≥ 5 mm in the greater curvature of the corpus. Nodularity was characterized by goosebump-like multiple nodules in the antrum. Diffuse redness was characterized by uniform reddish non-atrophic mucosa in the greater curvature of the corpus.

Results: A total of 266 gastric cancer patients (mean age, 66.7 years; male sex, 58.6%; mean body mass index, 22.8 kg/m) were enrolled. Ninety-three patients underwent esophagogastroduodenoscopy for surveillance within 2 years, and 140 had current infection. The mean Kyoto score was 4.54. Fifty-eight cancers were diffuse-type, and 87 cancers had invaded the submucosa. Multivariate analysis revealed that low body mass index (odds ratio 0.88, = 0.02), no surveillance esophagogastroduodenoscopy within 2 years (odds ratio 0.15, < 0.001), endoscopic enlarged folds of gastritis (odds ratio 3.39, = 0.001), and Lauren's diffuse-type (odds ratio 5.09, < 0.001) were independently associated with submucosal invasion. Similar results were obtained with curative endoscopic resection. Among cancer patients with enlarged folds, severely enlarged folds (width ≥ 10 mm) were more related to submucosal invasion than mildly enlarged folds (width 5-9 mm, < 0.001).

Conclusion: Enlarged folds of gastritis were associated with submucosal invasion. Endoscopic observation of background gastritis as well as the lesion itself may help diagnose the depth of cancer invasion.
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http://dx.doi.org/10.4253/wjge.v13.i9.426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474696PMC
September 2021

Artificial intelligence versus expert endoscopists for diagnosis of gastric cancer in patients who underwent upper gastrointestinal endoscopy.

Endoscopy 2021 Oct 4. Epub 2021 Oct 4.

Gastroenterology, University of Tokyo, Tokyo, Japan.

Introduction And Aims: To compare endoscopy gastric cancer images diagnosis rate between artificial intelligence (AI) and expert endoscopists.

Patients And Methods: We used the retrospective data of 500 patients, including 100 with gastric cancer, matched 1:1 to diagnosis by AI or expert endoscopists. We retrospectively evaluated the non-inferiority (prespecified margin 5%) of the per-patient rate of gastric cancer diagnosis by AI and compared the per-image rate of gastric cancer diagnosis.

Results: Gastric cancer was diagnosed in 49 of 49 patients (100%) in the AI group and 48 of 51 patients (94.12%) in the expert endoscopist group (difference 5.88, 95% confidence interval: -0.58 to 12.3). The per-image rate of gastric cancer diagnosis was higher in the AI group (99.87%, 747/748 images) than in the expert endoscopist group (88.17%, 693/786 images) (difference 11.7%).

Conclusions: Non inferiority of the rate of gastric cancer diagnosis by AI was demonstrated but superiority is not demonstrated.
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http://dx.doi.org/10.1055/a-1660-6500DOI Listing
October 2021

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020.

J Gastroenterol 2021 Nov 17;56(11):951-963. Epub 2021 Sep 17.

Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease (CVD) event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary provides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.
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http://dx.doi.org/10.1007/s00535-021-01796-xDOI Listing
November 2021

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020.

Hepatol Res 2021 Oct 17;51(10):1013-1025. Epub 2021 Sep 17.

Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan.

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro- vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.
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http://dx.doi.org/10.1111/hepr.13688DOI Listing
October 2021

The feasibility of a novel injectable hydrogel for protecting artificial gastrointestinal ulcers after endoscopic resection: an animal pilot study.

Sci Rep 2021 09 16;11(1):18508. Epub 2021 Sep 16.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Recently, covering materials for protecting post-endoscopic ulcers are being developed using hydrogels. Existing hydrogels are not ideal coating materials because it is difficult to control their physical properties. Therefore, we conducted an animal pilot study to investigate the protective effect of a novel ulcer coating material, whose physical properties can be easily controlled and designed. We applied the novel injectable hydrogel to artificial ulcers induced on the gastric mucosa of rats. Rats were assigned to the hydrogel or the control group. To measure the protective effect of hydrogel on ulcers, the perforation rate, ulcer diameter, and ulcer area were evaluated 48 h after gel application. As secondary endpoints, we assessed the residual rate of the hydrogel at the bottom of the ulcer, performed histological analysis, and analyzed adverse events associated with hydrogel. The perforation rate was significantly lower (16% vs. 75%) and the mean diameter of ulcers was significantly smaller (5.4 ± 1.8 mm vs. 7.8 ± 2.8 mm) in the hydrogel group. Histopathological findings revealed the inflammatory cell count was significantly higher in the control group. Our novel hydrogel showed a protective effect on artificial gastric ulcers in a rat model.
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http://dx.doi.org/10.1038/s41598-021-97988-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445931PMC
September 2021

HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA.

J Hepatol 2021 Aug 31. Epub 2021 Aug 31.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Background & Aims: HBV causes hepatocellular carcinoma (HCC). While it was recently shown that the ability of HBV X protein (HBx) to impair the Smc5/6 (structural maintenance of chromosome 5/6) complex is important for viral transcription, HBx is also a potent driver of HCC. However, the mechanism by which HBx expression induces hepatocarcinogenesis is unclear.

Methods: Degradation of the Smc5/6 complex and accumulation of DNA damage were observed in both in vivo and in vitro HBV infection models. Rescue experiments were performed using nitazoxanide (NTZ), which inhibits degradation of the Smc5/6 complex by HBx.

Results: HBx-triggered degradation of the Smc5/6 complex causes impaired homologous recombination (HR) repair of DNA double-strand breaks (DSBs), leading to cellular transformation. We found that DNA damage accumulated in the liver tissue of HBV-infected humanized chimeric mice, HBx-transgenic mice, and human tissues. HBx suppressed the HR repair of DSBs, including that induced by the CRISPR-Cas9 system, in an Smc5/6-dependent manner, which was rescued by restoring the Smc5/6 complex. NTZ restored HR repair in, and colony formation by, HBx-expressing cells.

Conclusions: Degradation of the Smc5/6 complex by HBx increases viral transcription and promotes cellular transformation by impairing HR repair of DSBs.

Lay Summary: The hepatitis B virus expresses a regulatory protein called HBV X protein (or HBx). This protein degrades the Smc5/6 complex in human hepatocytes, which is essential for viral replication. We found that this process also plays a key role in the accumulation of DNA damage, which contributes to HBx-mediated tumorigenesis.
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http://dx.doi.org/10.1016/j.jhep.2021.08.010DOI Listing
August 2021

Incidence and computed tomography findings of lenvatinib-induced pancreatobiliary inflammation: A single-center, retrospective study.

Medicine (Baltimore) 2021 Sep;100(35):e27182

Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Abstract: In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.We included 78 patients (mean ± standard deviation, 69.8 ± 9.4 years, range: 39-84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016-September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future.
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http://dx.doi.org/10.1097/MD.0000000000027182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415931PMC
September 2021

Changing clinical management of NAFLD in Asia.

Liver Int 2021 Aug 29. Epub 2021 Aug 29.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, affecting approximately 25% of the world's population. Recently, because of the sedentary lifestyle and overnutrition resulting from urbanisation, the burden of NAFLD has rapidly increased in many Asian countries. Currently, the prevalence of NAFLD in Asia is approximately 30%, as is the case in many Western countries. In Asia, the prevalence and presentation of NAFLD vary widely across regions because of the substantial diversity in race, socioeconomic status and living environment. Furthermore, the dual aetiology of fatty liver, particularly with viral hepatitis in Asia, makes it complex and challenging to manage. Because Asians are likely to have central adiposity and insulin resistance, approximately 7%-20% of non-obese Asians with body mass indexes of less than 25 kg/m are estimated to have NAFLD. Accumulating evidence indicates that NAFLD is associated with various extrahepatic comorbidities such as cardiovascular disease, chronic kidney disease, malignancy, in addition to liver-specific complications. Therefore, NAFLD should be managed as a multisystem disease in conjunction with metabolic syndrome. Lifestyle modification remains the basis of NAFLD management, but few patients can achieve adequate weight loss and maintain it long term. While various pharmacological agents are in phase 3 trials for steatohepatitis, Asian patients are underrepresented in most trials. This article reviews the epidemiological trends, clinical features, optimal assessment and current management practices for NAFLD in Asia.
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http://dx.doi.org/10.1111/liv.15046DOI Listing
August 2021

Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals.

Liver Cancer 2021 Jul 4;10(4):309-319. Epub 2021 Jun 4.

Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan.

Background And Aims: It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy.

Methods: In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively.

Results: Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51-4.25) and 2.56 (95% CI: 1.14-5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61-2.33).

Conclusions: Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.
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http://dx.doi.org/10.1159/000513705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339497PMC
July 2021

Comparison of inflammatory bowel disease relapse after top-down or step-up therapy: a population-based cohort study.

Int J Colorectal Dis 2021 Oct 13;36(10):2227-2235. Epub 2021 Aug 13.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Purpose: The therapeutic effect of top-down therapy for inflammatory bowel disease (IBD) has not been fully evaluated in real-world clinical settings. We compared the effectiveness of top-down and step-up therapies for IBD.

Methods: We retrospectively evaluated patients who were admitted with IBD (Crohn's disease [CD] or ulcerative colitis [UC]) between 2012 and 2019 using the nationwide Japan Diagnosis Procedure Combination database. Patients who received immunomodulators or biologic agents at the start of observation were assigned to the top-down group and those who did not were enrolled in the step-up group. Relapse was the primary outcome, a composite outcome defined as surgery, new steroid or immunomodulator use, hospitalization, a new biologic agent, or switching biologic agents.

Results: We analyzed 6715 patients (CD, N = 3643; UC, N = 3072). Relapse occurred in 1982 CD cases (54.4%). The cumulative CD relapse incidence was 32.9% at 1 year and 61.3% at 5 years in the top-down group and 30.7% at 1 year and 58.6% at 5 years in the step-up group. Relapse occurred in 2032 UC cases (47.8%). The cumulative relapse incidence was 33.5% at 1 year and 50.0% at 5 years in the top-down group and 35.2% at 1 year and 51.6% at 5 years in the step-up group. No clinical factors associated with relapse were identified in patients with CD or UC.

Conclusion: Compared with step-up therapy, top-down therapy was not associated with a decreased relapse risk in a real-world population of patients with CD or UC.
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http://dx.doi.org/10.1007/s00384-021-04007-4DOI Listing
October 2021

Use of proton pump inhibitors and cholangitis complicated with multi-drug resistant bacteria.

J Hepatobiliary Pancreat Sci 2021 Aug 12. Epub 2021 Aug 12.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Multidrug-resistant bacteria (MDRB) has rapidly spread worldwide and become a serious problem. Proton pump inhibitors (PPIs) are a class of commonly prescribed medications, but recent studies have suggested the increased risk of infection with MDRB in PPI users. We evaluated the association between PPI use and incidence of cholangitis with MDRB.

Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2010 and August 2019 were included in this retrospective study. The incidence of cholangitis with MDRB was compared between regular and non-regular PPI users.

Results: A total of 1224 regular PPI users and 1528 non-regular PPI users were identified. There was no clinically significant difference in age and sex between the groups. Indication of ERCP was different between the groups. The number of ERCP sessions during the study periods was higher in regular PPI users. The incidence of cholangitis with MDRB was significantly higher in regular PPI users (3.0% vs 1.1%; P < .001). Multivariable-adjusted odds ratio for cholangitis with MDRB comparing regular PPI users to non-regular users was 2.19 (95% confidence interval 1.20-4.00; P = .01).

Conclusions: Regular PPI use was associated with a higher risk of cholangitis with MDRB.
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http://dx.doi.org/10.1002/jhbp.1035DOI Listing
August 2021

Cell fate analysis of zone 3 hepatocytes in liver injury and tumorigenesis.

JHEP Rep 2021 Aug 27;3(4):100315. Epub 2021 May 27.

Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.

Background & Aims: Liver lobules are typically subdivided into 3 metabolic zones: zones 1, 2, and 3. However, the contribution of zonal differences in hepatocytes to liver regeneration, as well as to carcinogenic susceptibility, remains unclear.

Methods: We developed a new method for sustained genetic labelling of zone 3 hepatocytes and performed fate tracing to monitor these cells in multiple mouse liver tumour models.

Results: We first examined changes in the zonal distribution of the Wnt target gene over time using mice (). We found that following tamoxifen administration at 3 weeks of age, approximately one-third of total hepatocytes that correspond to zone 3 were labelled in mice; the tdTomato cell distribution closely matched that of the zone 3 marker CYP2E1. Cell fate analysis revealed that zone 3 hepatocytes maintained their own lineage but rarely proliferated beyond their liver zonation during homoeostasis; this indicated that our protocol enabled persistent genetic labelling of zone 3 hepatocytes. Using this system, we found that zone 3 hepatocytes generally had high neoplastic potential, which was promoted by constitutive activation of Wnt/β-catenin signalling in the pericentral area. However, the frequency of zone 3 hepatocyte-derived tumours varied depending on the regeneration pattern of the liver parenchyma in response to liver injury. Notably, Axin2-expressing hepatocytes undergoing chronic liver injury significantly contributed to liver regeneration and possessed high neoplastic potential. Additionally, we revealed that the metabolic phenotypes of liver tumours were acquired during tumorigenesis, irrespective of their spatial origin.

Conclusions: Hepatocytes receiving Wnt/β-catenin signalling from their microenvironment have high neoplastic potential, and Wnt/β-catenin signalling is a potential drug target for the prevention of hepatocellular carcinoma.

Lay Summary: Lineage tracing revealed that zone 3 hepatocytes residing in the pericentral niche have high neoplastic potential. Under chronic liver injury, hepatocytes receiving Wnt/β-catenin signalling broadly exist across all hepatic zones and significantly contribute to liver tumorigenesis as well as liver regeneration. Wnt/β-catenin signalling is a potential drug target for the prevention of hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.jhepr.2021.100315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319533PMC
August 2021

Humanized virus-suppressing factor inhibits hepatitis B virus infection by targeting viral cell entry.

Heliyon 2021 Jul 14;7(7):e07586. Epub 2021 Jul 14.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Although nucleos(t)ide analogs and interferons suppress hepatitis B virus (HBV) replication, they must be taken continuously and have a low response rate. Therefore, therapeutics for HBV with novel modes of action are needed. Humanized virus-suppressing factor (hzVSF) is a monoclonal antibody against vimentin that exhibits broad-spectrum antiviral activity. Here, hzVSF significantly inhibited HBV infection. Although hzVSF inhibited HBV RNA production, it did not affect viral transcription from minicircle DNA mimicking covalently closed circular DNA. Additionally, hzVSF did not inhibit viral protein or DNA release from infected cells. Rather, hzVSF inhibited the cell entry of viral preS1 peptides, possibly by altering intracellular vimentin localization, which is important for HBV cell entry. These results suggest that hzVSF has therapeutic potential for HBV infection with a novel mode of action.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319007PMC
July 2021

Letter: predictive model for gastric cancer after eradication of Helicobacter pylori-a survival analysis using a deep learning algorithm.

Aliment Pharmacol Ther 2021 08;54(4):528-529

Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1111/apt.16492DOI Listing
August 2021

Limited efficacy of atezolizumab and bevacizumab for hepatocellular carcinoma previously treated with tyrosine kinase inhibitor.

Liver Int 2021 09 20;41(9):2233-2234. Epub 2021 Jul 20.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1111/liv.15010DOI Listing
September 2021

The "zipline" technique for double-balloon enteroscopy-assisted removal of a migrated stent in a peripheral bile duct.

Endoscopy 2021 Jul 19. Epub 2021 Jul 19.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1055/a-1530-4969DOI Listing
July 2021

Protein intake after the initiation of chemotherapy is an independent prognostic factor for overall survival in patients with unresectable pancreatic cancer: A prospective cohort study.

Clin Nutr 2021 07 17;40(7):4792-4798. Epub 2021 Jun 17.

Clinical Nutrition Center, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. Electronic address:

Background & Aims: This study was conducted to investigate the nutritional status and longitudinal dietary intake during the course of chemotherapy, and their relationships with the survival in patients with unresectable pancreatic cancer.

Methods: A prospective cohort study was conducted in 38 patients with unresectable pancreatic cancer receiving chemotherapy between January 2018 and November 2019. Subjective global assessment was used to assess the nutritional status, and the dietary intake was assessed monthly, for up to 12 months, using a brief self-administered diet history questionnaire. The primary outcome was overall survival, and the secondary outcome was progression-free survival. Cox regression analysis was performed to identify independent prognostic factors.

Results: Moderate or severe malnutrition was found in 34.2% of the participants. Daily protein intake was significantly higher in the survivor group than in the deceased group at one month after the initiation of chemotherapy (1.4 ± 0.7 g/kg/day vs. 0.9 ± 0.5 g/kg/day, p = 0.019), while the baseline nutritional intakes were similar between the two groups. Univariate analysis identified weight loss >3.5%, energy intake <25 kcal/kg/day, protein intake <1.1 g/kg/day, and malnutrition as possible poor prognostic factors. Multivariate analysis identified protein intake <1.1 g/kg/day (hazard ratio [HR]: 9.03, 95%CI: 1.45-56.32, p = 0.018) as an independent poor prognostic factor.

Conclusions: Insufficient protein intake was identified as an independent poor prognostic factor in patients with unresectable pancreatic cancer receiving chemotherapy. Improving the dietary protein intake could be a useful therapeutic approach in patients with advanced pancreatic cancer receiving chemotherapy.
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http://dx.doi.org/10.1016/j.clnu.2021.06.011DOI Listing
July 2021

Nonsteroidal anti-inflammatory drugs prevent gastric cancer associated with the use of proton pump inhibitors after eradication.

JGH Open 2021 Jul 5;5(7):770-777. Epub 2021 Jun 5.

Department of Gastroenterology, Graduate School of Medicine The University of Tokyo Bunkyo City Tokyo Japan.

Background And Aim: Proton pump inhibitors (PPIs) are a potential cause of gastric carcinogenesis after eradication. Thus, appropriate management including chemoprevention is required. The aim of this study was to evaluate the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the incidence of post-eradication gastric cancer in PPI users.

Methods: A multicenter retrospective cohort study was conducted. Patients who used a PPI (≥30 days) after eradication between 2014 and 2019 were analyzed in nine hospital databases. Gastric cancer incidence was a primary outcome, and their association with NSAIDs use and clinical factors was evaluated. Hazard ratios were adjusted by age, sex, smoking, and Charlson Comorbidity Index.

Results: During the mean follow-up period of 2.38 years, 1.13% (31/2431) of all patients developed gastric cancer. The cumulative incidence of gastric cancer in PPI users was 0.25% at 1 year, 0.51% at 3 years, and 1.09% at 5 years in the NSAID users and 0.89% at 1 year, 2.32% at 3 years, and 3.61% at 5 years in nonusers. NSAIDs were associated with a lower gastric cancer risk (adjusted hazard ratio = 0.28,  = 0.005). No gastric cancer was observed in the cyclooxygenase-2 inhibitor users ( = 256). NSAID use with high dose and long duration was significantly associated with a lower incidence of gastric cancer.

Conclusion: NSAIDs were associated with a 60% decrease in the gastric cancer incidence in -eradicated PPI users, with dose and duration response effects. NSAIDs may be effective for chemoprevention against PPI-related gastric cancer.
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http://dx.doi.org/10.1002/jgh3.12583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264245PMC
July 2021

Molecular and Phenotypic Profiling for Precision Medicine in Pancreatic Cancer: Current Advances and Future Perspectives.

Front Oncol 2021 23;11:682872. Epub 2021 Jun 23.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Pancreatic cancer is the most common lethal malignancy, with little improvement in patient outcomes over the decades. The development of early detection methods and effective therapeutic strategies are needed to improve the prognosis of patients with this disease. Recent advances in cancer genomics have revealed the genetic landscape of pancreatic cancer, and clinical trials are currently being conducted to match the treatment to underlying mutations. Liquid biopsy-based diagnosis is a promising method to start personalized treatment. In addition to genome-based medicine, personalized models have been studied as a tool to test candidate drugs to select the most efficacious treatment. The innovative three-dimensional organoid culture platform, as well as patient-derived xenografts can be used to conduct genomic and functional studies to enable personalized treatment approaches. Combining genome-based medicine with drug screening based on personalized models may fulfill the promise of precision medicine for pancreatic cancer.
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http://dx.doi.org/10.3389/fonc.2021.682872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260689PMC
June 2021

Orchestration of myeloid-derived suppressor cells in the tumor microenvironment by ubiquitous cellular protein TCTP released by tumor cells.

Nat Immunol 2021 08 8;22(8):947-957. Epub 2021 Jul 8.

Department of Inflammology, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.

One of most challenging issues in tumor immunology is a better understanding of the dynamics in the accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TIME), as this would lead to the development of new cancer therapeutics. Here, we show that translationally controlled tumor protein (TCTP) released by dying tumor cells is an immunomodulator crucial to full-blown MDSC accumulation in the TIME. We provide evidence that extracellular TCTP mediates recruitment of the polymorphonuclear MDSC (PMN-MDSC) population in the TIME via activation of Toll-like receptor-2. As further proof of principle, we show that inhibition of TCTP suppresses PMN-MDSC accumulation and tumor growth. In human cancers, we find an elevation of TCTP and an inverse correlation of TCTP gene dosage with antitumor immune signatures and clinical prognosis. This study reveals the hitherto poorly understood mechanism of the MDSC dynamics in the TIME, offering a new rationale for cancer immunotherapy.
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http://dx.doi.org/10.1038/s41590-021-00967-5DOI Listing
August 2021

Evidence-based clinical practice guidelines for Liver Cirrhosis 2020.

J Gastroenterol 2021 Jul 7;56(7):593-619. Epub 2021 Jul 7.

Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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http://dx.doi.org/10.1007/s00535-021-01788-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280040PMC
July 2021

Evidence-based clinical practice guidelines for liver cirrhosis 2020.

Hepatol Res 2021 Jul 6;51(7):725-749. Epub 2021 Jul 6.

Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan.

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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http://dx.doi.org/10.1111/hepr.13678DOI Listing
July 2021

Simple feedback of colonoscopy performance improved the number of adenomas per colonoscopy and serrated polyp detection rate.

Endosc Int Open 2021 Jul 17;9(7):E1032-E1038. Epub 2021 Jun 17.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

 High-quality endoscopy requires improvement of not only the adenoma detection rate (ADR) but also the serrated polyp (SP) detection rate and the mean number of adenomas per positive procedure (MAP +). We evaluated whether a simple feedback of colonoscopy performance improves those quality indicators using propensity-score matching.  Eleven endoscopists were evaluated regarding colonoscopy performance including ADRs, SP detection rates, mean numbers of adenomas per procedure (MAPs), and MAPs + with their ranking in the clinic. Endoscopic performance was compared before and after the feedback.  Colonoscopies were performed for 874 patients before the feedback and 1,272 patients after the feedback. Using propensity-score matching, 803 patients before the feedback and 803 patients after the feedback were matched. ADR after the feedback was significantly higher than that before the feedback (50.8 % and 40.8 %, respectively). MAP after feedback was significantly larger than that before the feedback (0.92 and 0.69, respectively), as well as MAP + (1.96 and 1.69, respectively). Clinically significant SP detection rate was also improved from 10.0 % to 14.9 %.  Feedback including ADR, MAP, MAP +, and clinically significant SR detection rate could improve on those quality indicators. Further studies are needed to effectively prevent colorectal cancer in colonoscopy practice.
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http://dx.doi.org/10.1055/a-1393-5469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211485PMC
July 2021

Clue of Diagnosis for Autoimmune Gastritis.

Digestion 2021 Jul 1:1-8. Epub 2021 Jul 1.

Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan.

Background: The diagnostic clues for autoimmune gastritis (AIG) can be classified into 2 categories: endoscopic findings and pathological diagnosis. We believe that research on the AIG detection rate by endoscopists could provide a better understanding of the diagnosis of AIG. This study aimed to clarify the ratio of the endoscopic and the pathological diagnoses of AIG.

Methods: We retrospectively reviewed consecutive patients who underwent esophagogastroduodenoscopy (EGD). During their first EGD, the gastric mucosa with C2 atrophy or more was biopsied for pathological evaluation based on the updated Sydney system. A gastric biopsy was also performed after Helicobacter pylori eradication, obtaining specimens from at least 2 sites, the greater curvature of the corpus and the antrum. We enrolled patients who were positive for the anti-parietal cell antibody and were diagnosed with AIG, histologically and/or endoscopically. The detection rates of AIG were compared between endoscopic diagnosis and pathological diagnosis.

Results: A total of 10,822 patients underwent EGD during the study period. Finally, 41 patients with AIG were enrolled, leading to an AIG prevalence of 0.38% in this study. As for the clue leading to AIG detection, 31.7% (13/41) were diagnosed through endoscopy (proximal-predominant atrophy), and 68.3% (28/41) were diagnosed pathologically. The AIG detection rate by endoscopists in the posteradication group was significantly lower than in the H. pylori-negative group (p < 0.05).

Conclusion: Endoscopists frequently overlooked AIG, especially in posteradication cases. Pathological assessment using the updated Sydney system after H. pylori eradication might be a promising strategy to detect AIG better.
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http://dx.doi.org/10.1159/000516624DOI Listing
July 2021

Use of Antibiotics and Probiotics Reduces the Risk of Metachronous Gastric Cancer after Endoscopic Resection.

Biology (Basel) 2021 May 22;10(6). Epub 2021 May 22.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38-0.85, = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091-0.91, = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development.
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http://dx.doi.org/10.3390/biology10060455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224738PMC
May 2021

Can Acropora tenuis larvae attract native Symbiodiniaceae cells by green fluorescence at the initial establishment of symbiosis?

PLoS One 2021 1;16(6):e0252514. Epub 2021 Jun 1.

Fisheries Technology Institute, Japan Fisheries Research and Education Agency, Ishigaki, Okinawa, Japan.

Most corals acquire symbiodiniacean symbionts from the surrounding environment to initiate symbiosis. The cell densities of Symbiodiniaceae in the environment are usually low, and mechanisms may exist by which new coral generations attract suitable endosymbionts. Phototaxis of suitable symbiodiniacean cells toward green fluorescence in corals has been proposed as one such mechanism. In the present study, we observed the phototaxis action wavelength of various strains of Symbiodiniaceae and the fluorescence spectra of aposymbiotic Acropora tenuis larvae at the time of endosymbiont uptake. The phototaxis patterns varied among the Symbiodiniaceae species and "native" endosymbionts-commonly found in Acropora juveniles present in natural environments; that is, Symbiodinium microadriaticum was attracted to blue light rather than to green light. Another native endosymbiont, Durusdinium trenchii, showed no phototaxis specific to any wavelength. Although the larvae exhibited green and broad orange fluorescence under blue-violet excitation light, the maximum green fluorescence peak did not coincide with that of the phototaxis action spectrum of S. microadriaticum. Rather, around the peak wavelength of larval green fluorescence, this native endosymbiont showed slightly negative phototaxis, suggesting that the green fluorescence of A. tenuis larvae may not play a role in the initial attraction of native endosymbionts. Conversely, broad blue larval fluorescence under UV-A excitation covered the maximum phototaxis action wavelength of S. microadriaticum. We also conducted infection tests using native endosymbionts and aposymbiotic larvae under red LED light that does not excite visible larval fluorescence. Almost all larvae failed to acquire S. microadriaticum cells, whereas D. trenchii cells were acquired by larvae even under red illumination. Thus, attraction mechanisms other than visible fluorescence might exist, at least in the case of D. trenchii. Our results suggest that further investigation and discussion, not limited to green fluorescence, would be required to elucidate the initial attraction mechanisms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252514PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168901PMC
June 2021

Triple stent-in-stent placement of novel braided metal stents with a slim delivery system via balloon-assisted enteroscopy.

Endoscopy 2021 May 31. Epub 2021 May 31.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1055/a-1492-1911DOI Listing
May 2021

Reduced handgrip strength predicts poorer survival in chronic liver diseases: A large multicenter study in Japan.

Hepatol Res 2021 Sep 12;51(9):957-967. Epub 2021 Jul 12.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aim: Sarcopenia has a high prevalence and can be an adverse predictor in patients with chronic liver diseases (CLDs). We sought to assess the prevalence of sarcopenia and its prognostic significance in patients with CLDs at multiple centers in Japan.

Methods: In this retrospective study, we collated the data of 1624 patients with CLDs (976 men). The diagnosis of sarcopenia was determined by the sarcopenia assessment criteria of the Japan Society of Hepatology. Predictors of mortality were identified using univariate and multivariate analyses.

Results: Muscle weakness and skeletal muscle loss occurred in 33.5% and 29.3% of all subjects, respectively, while sarcopenia occurred in 13.9% of all patients. Patients with sarcopenia had a poorer prognosis among all patients, patients with hepatocellular carcinoma (HCC), and those without HCC by log-rank test. The multivariate Cox proportional hazards model identified female gender (hazard ratio [HR], 0.59; p = 0.03), alcoholic liver disease (HR, 4.25; p < 0.01), presence of HCC (HR, 6.77; p < 0.01), Child-Pugh classes A (HR, 1.42; p < 0.05), B (HR, 2.70; p < 0.01), and C (HR, 6.30; p < 0.01), and muscle weakness (HR, 2.24; p < 0.01) as significant adverse predictors. The cut-off values of handgrip strength (HGS) for prognosis determined by maximally selected rank statistics were calculated as 27.8 kg for men and 18.8 kg for women.

Conclusion: Reduced HGS in patients with CLD was an independent adverse predictor of mortality, with cut-off values of 27.8 kg for men and 18.8 kg for women.
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http://dx.doi.org/10.1111/hepr.13679DOI Listing
September 2021

A safe sequential treatment approach for patients who have acute cholecystitis with severe inflammation: Transmural gallbladder drainage followed by laparoscopic cholecystectomy under the guidance of fluorescence imaging.

Asian J Endosc Surg 2021 May 30. Epub 2021 May 30.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

Introduction: For patients who have acute severe cholecystitis, urgent/early biliary drainage followed by delayed/elective laparoscopic cholecystectomy is recommended according to the Tokyo Guidelines 2018. Percutaneous transhepatic gallbladder drainage is an established technique. Recently, transmural gallbladder drainage under the guidance of endoscopic ultrasonography (EUS-GBD) was reported as a safe alternative. During surgery, fluorescence imaging using indocyanine green (ICG) has been increasingly used for visualizing the bile ducts. Herein, we report a sequential treatment approach which ensures safety without impairing normal activities before cholecystectomy: EUS-GBD followed by laparoscopic cholecystectomy using ICG fluorescence imaging.

Materials And Surgical Technique: A 66-year-old man with acute cholecystitis underwent urgent EUS-GBD and had the drainage tube placement through the duodenum into the gallbladder. During 2.5 months of the waiting period, he had no clinical troubles. After insertion of a laparoscope, we found a structure between the gallbladder and the duodenum. We injected 0.025 mg/mL of ICG into the nasobiliary drainage tube (placed in the gallbladder through the duodenum) and confirmed that the structure was a fistula. After removing the tube, the fistula was divided using a surgical stapler under the guidance of fluorescence imaging. The cystic and common bile ducts were also clearly visualized as fluorescence.

Discussion: We reported a safe sequential treatment approach for the patient who required biliary drainage: EUS-GBD followed by laparoscopic cholecystectomy under the guidance of ICG fluorescence imaging. This sequential approach may improve patients' satisfaction with respect to quality of life during the waiting period and may ensure the safety of laparoscopic cholecystectomy.
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http://dx.doi.org/10.1111/ases.12955DOI Listing
May 2021

Comparison of endoscopic gastritis based on Kyoto classification between diffuse and intestinal gastric cancer.

World J Gastrointest Endosc 2021 May;13(5):125-136

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Background: Gastric cancers can be categorized into diffuse- and intestinal-type cancers based on the Lauren histopathological classification. These two subtypes show distinct differences in metastasis frequency, treatment application, and prognosis. Therefore, accurately assessing the Lauren classification before treatment is crucial. However, studies on the gastritis endoscopy-based Kyoto classification have recently shown that endoscopic diagnosis has improved.

Aim: To investigate patient characteristics including endoscopic gastritis associated with diffuse- and intestinal-type gastric cancers in ()-infected patients.

Methods: Patients who underwent esophagogastroduodenoscopy at the Toyoshima Endoscopy Clinic were enrolled. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. The effects of age, sex, and Kyoto classification score on gastric cancer according to the Lauren classification were analyzed. We developed the Lauren predictive background score based on the coefficients of a logistic regression model using variables independently associated with the Lauren classification. Area under the receiver operative characteristic curve and diagnostic accuracy of this score were examined.

Results: A total of 499 -infected patients (49.6% males; average age: 54.9 years) were enrolled; 132 patients with gastric cancer (39 diffuse- and 93 intestinal-type cancers) and 367 cancer-free controls were eligible. Gastric cancer was independently associated with age ≥ 65 years, high atrophy score, high intestinal metaplasia score, and low nodularity score when compared to the control. Factors independently associated with intestinal-type cancer were age ≥ 65 years (coefficient: 1.98), male sex (coefficient: 1.02), high intestinal metaplasia score (coefficient: 0.68), and low enlarged folds score (coefficient: -1.31) when compared to diffuse-type cancer. The Lauren predictive background score was defined as the sum of +2 (age ≥ 65 years), +1 (male sex), +1 (endoscopic intestinal metaplasia), and -1 (endoscopic enlarged folds) points. Area under the receiver operative characteristic curve of the Lauren predictive background score was 0.828 for predicting intestinal-type cancer. With a cut-off value of +2, the sensitivity, specificity, and accuracy of the Lauren predictive background score were 81.7%, 71.8%, and 78.8%, respectively.

Conclusion: Patient backgrounds, such as age, sex, endoscopic intestinal metaplasia, and endoscopic enlarged folds are useful for predicting the Lauren type of gastric cancer.
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http://dx.doi.org/10.4253/wjge.v13.i5.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134854PMC
May 2021
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