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Background and study aims Among colorectal serrated polyps (SPs), sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) have a similar endoscopic appearance. However, the endoscopic distinctions between those two categories, microvesicular HPs (MVHPs) and goblet cell-rich HPs (GCHPs), are not well understood. Therefore, we compared the endoscopic features of SSLs, MVHPs, and GCHPs. Methods This retrospective, cross-sectional study was conducted at the Toyoshima Endoscopy Clinic. We examined polyp size, location, Paris classification type, mucus cap, indistinct border, expanded crypt opening, varicose microvascular vessels, and JNET classification type. Multivariable analysis of each endoscopic finding using a binomial logistic regression model determined the factors that predicted SP histology. Results A total of 670 SPs were enrolled in this study, comprising 159 SSLs, 361 MVHPs, and 150 GCHPs. On comparing the SSL + MVHP group and the GCHP group, a mucus cap (partial regression coefficient 1.705), expanded crypt opening (1.828), and varicose microvascular vessels (1.270) were more often observed in the SSL + MVHP group compared with the GCHP group. In the comparison between MVHPs and GCHPs, a mucus cap (1.564), expanded crypt opening (1.802), and varicose microvascular vessels (1.288) were more often found in MVHPs in contrast to GCHPs. When comparing SSLs and MVHPs, SSLs were more likely to be in the proximal colon (0.662) and were larger (0.198) than the MVHPs. No significant differences were observed in other endoscopic findings. Conclusions SSLs and MVHPs have endoscopic appearances that differ from those of GCHPs. Considering MVHPs and GCHPs as distinct entities may aid in endoscopic diagnosis of SPs., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective We previously reported that patients with acute leukemia and malignant lymphoma (ML) demonstrated significantly increased serum soluble LR11 (sLR11) levels compared to normal controls. Accurately diagnosing ML of the central nervous system (CNS ML) using cytology is frequently difficult. Therefore, we evaluated the use of cerebrospinal fluid (CSF) sLR11 and soluble interleukin-2 receptor (sIL-2R) as diagnostic and treatment response markers for CNS ML. Methods We retrospectively evaluated the CSF results for CNS ML using clinical data at our institution, and then analyzed the usefulness of sLR11 and sIL-2R in CSF for both the diagnosis and as surrogate markers that reflect the therapeutic effect. Patients We enrolled patients with CNS ML who received intrathecal anticancer drugs between 2017 and 2023. We analyzed the sLR11 and sIL-2R levels in CSF and cytological malignant grades. We studied 22 patients, including 17 with central nervous system (CNS) clinical conditions and five who received prevention treatment. Results The CSF sLR11 levels were significantly and positively correlated with CSF sIL-2R levels. The CSF sLR11 and sIL-2R levels in patients with CNS ML were significantly higher than those in the prevention group. A receiver operating characteristic (ROC) curve analysis showed the cut-off value of sLR11 for CNS invasion to be 21.7 ng/mL. Moreover, the chemotherapy-responder group demonstrated significantly decreased CSF sLR11 and sIL-2R levels after treatment. Conclusion CSF sLR11 and sIL-2R of CSF were found to be useful biomarkers for the diagnostic and treatment response evaluation in patients with CNS ML.

Background and Aim: Few studies have evaluated the adenoma detection rate (ADR) of colonoscopy with texture and color enhancement imaging (TXI), a novel image-enhancing technology. This study compares the detection of colorectal polyps using TXI to that using white light imaging (WLI)., Methods: This single-center retrospective study used propensity-matched scoring based on the patients' baseline characteristics (age, sex, indication, bowel preparation, endoscopist, colonoscope type, and withdrawal time) to compare the results of patients who underwent chromoendoscopy using WLI or TXI at the Toyoshima Endoscopy Clinic. The differences in polyp detection rates and the mean number of detected polyps per colonoscopy were determined between the TXI and WLI groups., Results: After propensity score matching, 1970 patients were enrolled into each imaging modality group. The mean patient age was 57.2 ± 12.5 years, and 44.5% of the cohort were men. The ADR was higher in the TXI group than in the WLI group (55.0% vs 49.4%, odds ratio: 1.25). High-risk ADR were more common in the TXI group than in the WLI group (17.6% vs 12.8%; OR: 1.45). The mean number of adenomas per colonoscopy (APC) was higher in the TXI group than in the WLI group (1.187 vs 0.943, OR: 1.12). APC with a flat morphology (1.093 vs 0.848, OR: 1.14) and APC of <6 mm (0.992 vs 0.757, OR: 1.16) were higher in the TXI group than in the WLI group., Conclusion: Compared to WLI, TXI improved the ADR in patients who underwent chromoendoscopy based on actual clinical data., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: We previously reported unusual adenomas with proliferative zones confined to the lower two-thirds of the crypt. The proliferative zones of colorectal adenomas have three patterns: 'lower,' 'superficial' and 'entire'. This study aimed to clarify the characteristics of each adenoma pattern., Methods: We investigated 2925 consecutive patients who underwent colonoscopy at our institute. All polyps that were removed were histologically examined using hematoxylin and eosin staining. The location of the proliferative zone was assessed for adenomas. Data were compared using Dunn's and Kruskal-Wallis tests., Results: Colorectal adenomas with 'lower' proliferative zone often appeared similar to hyperplastic polyps (42.8%), and the frequency was significantly higher than that of adenomas with 'superficial' and 'entire' proliferative zones ( p  < 0.001). The mean sizes of adenomas were 2.4, 3.0 and 3.9 mm for 'lower,' 'superficial' and 'entire' proliferative zones, respectively. A significant gradual increase was observed. Regarding morphology, the proportion of type 0-I in adenomas with an 'entire' proliferative zone was significantly higher than that in adenomas with 'superficial' proliferative zone ( p  < 0.001)., Conclusion: While colorectal adenomas develop and increase in size, the proliferative zone appears to shift upward and become scattered.

Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child-Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child-Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44-2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3-5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes., (© 2024. The Author(s).)

Background: The proliferative zone of colonic adenomas is confined to the upper third of the crypt or is scattered along its entire axis. In contrast, there are unusual adenomas with proliferative zones confined to the lower two-thirds of the crypt. We investigated the frequency and endoscopic features of adenomas with lower proliferative zones., Methods: We retrospectively reviewed consecutive patients who underwent colonoscopies between September 2022 and March 2023 at the Toyoshima Endoscopy Clinic. Colorectal polyps were endoscopically assessed using the Japan Narrow-Band Imaging Expert Team (JNET) classification. All resected polyps were histologically examined, and the proliferative zone locations were assessed in the adenomas., Results: The frequency of adenomas with a lower proliferative zone was 1.8% (44/2420) in adenomas. Among these adenomas, JNET type 1 incidence was 43.2% (19/44), which was significantly higher than that in adenomas with a normal proliferative zone. Adenomas with a lower proliferative zone were diminutive (mean size: 2.5 mm) and prone to develop in the proximal colon., Conclusion: Colonic adenomas with proliferative zones confined to the lower two-thirds of the crypt often appear as diminutive, hyperplastic polyps.

Background: Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation., Methods: This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated., Results: 13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.217.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20-25) to 15 (13-21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= -0.9943, p<0.0001) but not before GMA (p=0.62)., Conclusions: Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words)., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Accurate diagnosis and early resection of colorectal polyps are important to prevent the occurrence of colorectal cancer. However, technical factors and morphological factors of polyps itself can lead to missed diagnoses. Image-enhanced endoscopy and chromoendoscopy (CE) have been developed to facilitate an accurate diagnosis. There have been no reports on visibility using a combination of texture and color enhancement imaging (TXI) and CE for colorectal tumors., Aim: To investigate the visibility of margins and surfaces with the combination of TXI and CE for colorectal lesions., Methods: This retrospective study included patients who underwent lower gastrointestinal endoscopy at the Toyoshima Endoscopy Clinic. We extracted polyps that were resected and diagnosed as adenomas or serrated polyps (hyperplastic polyps and sessile serrated lesions) from our endoscopic database. An expert endoscopist performed the lower gastrointestinal endoscopies and observed the lesion using white light imaging (WLI), TXI, CE, and TXI + CE modalities. Indigo carmine dye was used for CE. Three expert endoscopists rated the visibility of the margin and surface patterns in four ranks, from 1 to 4. The primary outcomes were the average visibility scores for the margin and surface patterns based on the WLI, TXI, CE, and TXI + CE observations. Visibility scores between the four modalities were compared by the Kruskal-Wallis and Dunn tests., Results: A total of 48 patients with 81 polyps were assessed. The histological subtypes included 50 tubular adenomas, 16 hyperplastic polyps, and 15 sessile serrated lesions. The visibility scores for the margins based on WLI, TXI, CE, and TXI + CE were 2.44 ± 0.93, 2.90 ± 0.93, 3.37 ± 0.74, and 3.75 ± 0.49, respectively. The visibility scores for the surface based on WLI, TXI, CE, and TXI + CE were 2.25 ± 0.80, 2.84 ± 0.84, 3.12 ± 0.72, and 3.51 ± 0.60, respectively. The visibility scores for the detection and surface on TXI were significantly lower than that on CE but higher than that on WLI ( P < 0.001). The visibility scores for the margin and surface on TXI + CE were significantly higher than those on CE ( P < 0.001). In the sub-analysis of adenomas, the visibility for the margin and surface on TXI + CE was significantly better than that on WLI, TXI, and CE ( P < 0.001). In the sub-analysis of serrated polyps, the visibility for the margin and surface on TXI + CE was also significantly better than that on WLI, TXI, and CE ( P < 0.001)., Conclusion: TXI + CE enhanced the visibility of the margin and surface compared to WLI, TXI, and CE for colorectal lesions., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Gastric cancer (GC) incidence based on the endoscopic Kyoto classification of gastritis has not been systematically investigated using time-to-event analysis., Aim: To examine GC incidence in an endoscopic surveillance cohort., Methods: This study was retrospectively conducted at the Toyoshima Endoscopy Clinic. Patients who underwent two or more esophagogastroduodenoscopies were enrolled. GC incidence was based on Kyoto classification scores, such as atrophy, intestinal metaplasia (IM), enlarged folds (EFs), nodularity, diffuse redness (DR), and total Kyoto scores. Hazard ratios (HRs) adjusted for age and sex were calculated using a Cox hazard model., Results: A total of 6718 patients were enrolled (median age 54.0 years; men 44.2%). During the follow-up period (max 5.02 years; median 2.56 years), GC developed in 34 patients. The average frequency of GCs per year was 0.19%. Kyoto atrophy scores 1 [HR with score 0 as reference: 3.66, 95% confidence interval (CI): 1.06 to 12.61], 2 (11.60, 3.82-35.27), IM score 2 (9.92, 4.37-22.54), EF score 1 (4.03, 1.63-9.96), DR scores 1 (6.22, 2.65-14.56), and 2 (10.01, 3.73-26.86) were associated with GC incidence, whereas nodularity scores were not. The total Kyoto scores of 4 (HR with total Kyoto scores 0-1 as reference: 6.23, 95%CI: 1.93 to 20.13, P = 0.002) and 5-8 (16.45, 6.29-43.03, P < 0.001) were more likely to develop GC, whereas the total Kyoto scores 2-3 were not. The HR of the total Kyoto score for developing GC per 1 rank was 1.75 (95%CI: 1.46 to 2.09, P < 0.001)., Conclusion: A high total Kyoto score (≥ 4) was associated with GC incidence. The endoscopy-based diagnosis of gastritis can stratify GC risk., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Percutaneous treatment of symptomatic hepatic cysts includes simple drainage and drainage with sclerosing agents. We compared the efficacy of simple drainage with that of drainage with minocycline infusion for treating symptomatic hepatic cysts. We retrospectively evaluated 11 patients who underwent percutaneous drainage of symptomatic hepatic cysts. In seven cases, minocycline infusion was added at the discretion of the clinician. Cyst volume was evaluated before drainage, immediately after drainage, and after long-term follow-up. Cyst volume was calculated before treatment by multiplying the orthogonal diameters using the ellipsoid formula. Relapse was defined as the regrowth of the cyst with symptoms. Cyst volume immediately after drainage and after long-term follow-up was significantly less than that before treatment for the drainage with minocycline infusion group ( p <0.05) but not for the simple drainage group. The relapse rates were 25% (1/4) for the simple drainage group and 0% for the drainage with minocycline infusion group. Drainage with minocycline infusion could be a promising option for treating symptomatic hepatic cysts, although simple drainage was not reliable., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2023 JCBN.)

In this review, we summarize up-to-date reports with five-year observation after colorectal endoscopic submucosal dissection (ESD). Five-year cause-specific survival rates ranged from 98.6 to 100%. The local recurrence rates ranged from 1.1 to 2.2% in complete resection and 7.5 to 25.0% in incomplete resection. Incomplete resection was a risk factor for local recurrence. In non-curative ESD, five-year cause-specific survival rates ranged from 93.8 to 100% with additional surgery, and 92.7 to 99.1% without surgery. The choice of additional surgery should be based on the individual patient's age, concomitant diseases, wishes, life expectancy, and the risk of lymph node metastasis. The metachronous cancer rates ranged from 0.22 to 1.1%. Both local recurrence and metachronous tumors should be checked with a follow-up colonoscopy after ESD.

Timely diagnosis and management of severe acute-onset autoimmune hepatitis (SA-AIH), a potential cause of acute liver failure (ALF), are challenging. An initial trial of corticosteroids (CS) followed by an assessment of clinical responses over 1-2 weeks is advocated by the latest international practice guidelines 1,2 and expert reviews. 3,4 Consideration of a second-line drug while evaluating for liver transplantation (LT) is also recommended. 2 Established predictors of "CS responsiveness" to guide decision-making are nonexistent. Herein, we determined the diagnostic abilities of early dynamics to define CS responsiveness in SA-AIH using the model for end-stage liver disease (MELD) scores., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The prevalence of Helicobacter pylori ( H. pylori ) has decreased during several decades due to improvements in the sanitary environment in Japan. Consequently, a relative increase in the incidence of H. pylori -uninfected gastric cancer is expected. We analyzed the trends in H. pylori -uninfected gastric cancer. Two hundred fifty-eight patients with gastric cancer were retrospectively analyzed. The study was divided into four periods: 2008-2011 (first period), 2012-2014 (second period), 2015-2017 (third period), and 2018-2021 (fourth period). The status of H. pylori infection was divided into four categories: uninfected, successful eradication, spontaneous eradication, and persistent infection. Gastric mucosal atrophy was divided into six grades according to the Kimura-Takemoto classification. The proportion of H. pylori infections significantly changed over the study period ( p  = 0.007). In particular, the rate of H. pylori -uninfected gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 13.4% in the first, second, third, and fourth periods, respectively; p  = 0.0013). The rate of no atrophy (C-0) in gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 11.0% in the first, second, third, and fourth periods, respectively; p  = 0.0046). In conclusion, the rate of H. pylori -uninfected gastric cancer without gastric atrophy tended to increase over time., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Background: Liver fibrosis is one of the cardinal clinical features of chronic hepatitis C (CHC). However, the mechanisms underlying the evolution and reversion of liver fibrosis after hepatitis C virus (HCV) eradication and their relationship with clinical outcomes and metabolic alterations are not fully elucidated. Whether any non-invasive fibrosis marker can predict prognosis is unknown., Methods: Between October 2014 and September 2019, 418 patients with CHC or compensated cirrhosis with HCV were prospectively recruited in this observational study. 326 patients that were successfully eradicated with interferon-free direct antiviral agents (IFN-free DAAs) were analyzed. Peri-treatment dynamics of serum levels of type IV collagen 7S fragment (4COL7S), a fibrosis marker, and subsequent clinical outcomes, including hepatic decompensation, newly emerged hepatocellular carcinoma (HCC), and all-cause mortality were analyzed., Results: Ten (3.1%) patients died during the observation period. 4COL7S-defined fibrosis progression (n = 97, 29.8%) at SVR was significantly correlated with worse all-cause mortality post-SVR (P = 0.0062) but not with the probability of newly emerged HCC (P = 0.24). Prognostic tendency was more prominent in patients with advanced fibrosis (P< 0.0001). 4COL7S-defined fibrosis progression at SVR and a baseline platelet count less than 10×104/μL were significantly predicted all-cause mortality (P = 0.0051). In exploratory analyses, a decreased 4COL7S at the end of treatment was correlated with a matrix-degrading phenotype that showed higher serum metalloproteinase to tissue inhibitors of metalloproteinase-1 ratios and characteristic metabolic fingerprints such as increased butyrate, some medium-chain fatty acids, anabolic amino acids, and decreased uremia toxins., Conclusions: Peri-treatment dynamics of serum 4COL7S, a non-invasive fibrosis marker, predict prognosis. Non-invasive fibrosis markers may be useful biomarkers for risk stratification post-SVR., Competing Interests: Y.K. is an employee at Mitsubishi Tanabe Pharma Corporation. The remaining authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Autoimmune gastritis (AIG) is histologically classified into three phases according to the severity of oxyntic mucosal atrophy: early, florid, and end phases. This study aimed to clarify the relationship between the AIG phase and the anti-parietal cell antibody titer., Methods: Patients who underwent upper gastrointestinal endoscopy were retrospectively reviewed in this study. We enrolled patients who were histologically diagnosed with AIG and serologically tested for anti-parietal cell antibody (APCA). AIG patients were classified into three groups: early, florid, and end phase groups. Clinical characteristics, including APCA titers, were compared among these three groups., Results: A total of 44 AIG patients were enrolled. There were two patients in the early phase, 11 in the florid phase, and 31 in the end phase. APCA-positive rates were 100% in the early phase, 90.9% in the florid phase, and 90.3% in the end phase. The mean APCA titer was 480 U in the early phase, 220 U in the florid phase, and 150 U in the end phase. There was a stepwise decrease in the APCA titer from the early phase to the end phase. The mean APCA titer for the end phase was significantly lower than that of the early phase or florid phase. Additionally, there was a stepwise decrease in serum gastrin levels from the early phase to the end phase., Conclusion: AIG progresses from the early phase to the end phase, and the APCA titer shows a decrease. The negativity of APCA could occur, especially in the end phase.

Background: Heart failure is a severe condition often involving pulmonary hypertension (PH). Soluble low-density lipoprotein receptor with 11 ligand-binding repeats (sLR11) has been associated with pulmonary artery hypertension. We examined whether sLR11 correlates with PH in left heart disease and can be used as a predictive marker., Method: We retrospectively analyzed patients with severe mitral regurgitation who underwent right heart catheterization before surgery for valve replacement or valvuloplasty from November 2005 to October 2012 at Juntendo University. We measured sLR11 levels before right heart catheterization and analyzed correlations with pulmonary hemodynamics. We compared prognoses between a group with normal sLR11 (≤9.4 ng/ml) and a group with high sLR11 (>9.4 ng/ml). Follow-up was continued for 5 years, with end points of hospitalization due to HF and death due to cardiovascular disease., Results: Among 34 patients who met the inclusion criteria, sLR11 correlated with mean pulmonary artery pressure (r = 0.54, p<0.001), transpulmonary pressure gradient (r = 0.42, p = 0.012), pulmonary vascular resistance (r = 0.36, p<0.05), and log brain natriuretic peptide (BNP). However, logBNP did not correlate with pulmonary vascular resistance (p = 0.6). Levels of sLR11 were significantly higher in the 10 patients with PH (14.4±4.3 ng/ml) than in patients without PH (9.9±3.9 ng/ml; p = 0.002). At 5 years, the event rate was higher in the high-sLR11 group than in the normal-sLR11 group. The high-sLR11 group showed 5 hospitalizations due to HF (25.0%) and 2 deaths (10.0%), whereas the normal-sLR11 group showed no hospitalizations or deaths. Analyses using receiver operating characteristic curves showed a higher area under the concentration-time curve (AUC) for sLR11 level (AUC = 0.85; 95% confidence interval (CI) = 0.72-0.98) than for BNP (AUC = 0.80, 95%CI = 0.62-0.99) in the diagnosis of PH in left heart disease., Conclusions: Concentration of sLR11 is associated with severity of PH and offers a strong predictor of severe mitral regurgitation in patients after surgery., Competing Interests: Hiroyuki Ebinuma is a paid employee of Tsukuba Research Institute, Sekisui Medical Co. Ltd. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Aim: Olympus Corporation released the texture and color enhancement imaging (TXI) technology as a novel image-enhancing endoscopic technique. We investigated the effectiveness of TXI in the imaging of serrated colorectal polyps, including sessile serrated lesions (SSLs)., Methods: Serrated colorectal polyps were observed using white light imaging (WLI), TXI, narrow-band imaging (NBI), and chromoendoscopy with and without magnification. Serrated polyps were histologically confirmed. TXI was compared with WLI, NBI, and chromoendoscopy for the visibility of the lesions without magnification and for that of the vessel and surface patterns with magnification. Three expert endoscopists evaluated the visibility scores, which were classified from 1 to 4., Results: Twenty-nine consecutive serrated polyps were evaluated. In the visibility score without magnification, TXI was significantly superior to WLI but inferior to chromoendoscopy in the imaging of serrated polyps and the sub-analysis of SSLs. In the visibility score for vessel patterns with magnification, TXI was significantly superior to WLI and chromoendoscopy in the imaging of serrated polyps and the sub-analysis of SSLs. In the visibility score for surface patterns with magnification, TXI was significantly superior to WLI but inferior to NBI in serrated polyps and in the sub-analysis of SSLs and hyperplastic polyps., Conclusions: TXI provided higher visibility than did WLI for serrated, colorectal polyps, including SSLs.

Background/aims: The recovery room used after endoscopy has limited capacity, and an efficient flow of the endoscopy unit is desired. We investigated the duration of hospital stay after endoscopy and the risk factors for prolonged hospital stay among outpatients., Methods: We retrospectively studied consecutive patients who underwent esophagogastroduodenoscopy or colonoscopy at the Toyoshima Endoscopy Clinic. We collected data on age, sex, body weight, midazolam and pethidine dosage, respiratory depression during endoscopy, and duration of hospital stay after endoscopy (scope out to check out). Risk factors for prolonged hospital stay (>100 minutes) were identified using multiple logistic regression analysis., Results: We enrolled 3,898 patients, including 3,517 (90.2%) patients tested under sedation and 381 (9.8%) patients tested without sedation. Overall, 442 (11.3%) patients had prolonged stay (>100 min). The mean time difference between sedation group and non-sedation group was 44.2 minutes for esophagogastroduodenoscopy and 39.1 minutes for colonoscopy. Age (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.014-1.036), female sex (OR, 1.657; 95% CI, 1.220-2.249), and midazolam dose (OR, 1.019; 95% CI, 1.013-1.026) were independently associated with prolonged hospital stay after esophagogastroduodenoscopy, with similar results for colonoscopy., Conclusion: Old age, female sex, and midazolam dose were independent risk factors for prolonged hospital stay after endoscopy.

Aim: Stereotactic body radiotherapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC) and has shown excellent local control (LC), as has radiofrequency ablation (RFA). As no randomized controlled trial has compared SBRT and RFA for HCC, data from a propensity score matched study (PSMS) are valuable. However, the results varied greatly and depended on composing factors of Barcelona Clinic Liver Cancer staging (BCLC-factors) adjusted. Therefore, we undertook a systematic review and meta-analyses of the studies focusing on BCLC-factors matching., Methods: We systematically searched PubMed, the Cochrane database, EMBASE, and Web of Science to identify studies comparing RFA and SBRT using propensity scores. The hazard ratios (HRs) of overall survival (OS) and LC from BCLC-factor-matched and -unmatched PSMS were pooled. Heterogeneity between the data from these studies was assessed., Results: Three BCLC-factor-matched studies were identified. Stereotactic body radiotherapy led to comparable OS (HR, 0.89; 95% CI, 0.74-1.08; p = 0.24; I 2  = 0%; p for heterogeneity, 0.56) and significantly better LC (HR, 0.39; 95% CI, 0.30-0.51; p < 0.001; I 2  = 0%; p for heterogeneity, 0.67). We also identified three additional BCLC-factor-unmatched studies (HR of OS, 1.41; 95% CI, 1.21-1.65; p < 0.0001; I 2  = 0%; p for heterogeneity, 0.63). However, considerable heterogeneity was observed for HR of OS between BCLC-factor-matched and -unmatched studies (I 2  = 92.6%; p for heterogeneity, 0.0002)., Conclusions: When BCLC-factors were properly adjusted, the results of the meta-analysis revealed equivalent OS and better LC for SBRT compared with RFA. Stereotactic body radiotherapy could be an alternative treatment option for HCC., (© 2021 The Japan Society of Hepatology.)

Background and Aim: Sitafloxacin-based therapy is a potent candidate for third-line Helicobacter pylori eradication treatment. In this systematic review, we summarise current reports with sitafloxacin-based therapy as a third-line treatment., Methods: Clinical studies were systematically searched using PubMed, Cochrane library, Web of Science, and the Igaku-Chuo-Zasshi database. We combined data from clinical studies using a random-effects model and calculated pooled event rates, 95% confidence intervals (CIs), and the pooled odds ratio (OR)., Results: We included twelve clinical studies in the present systematic review. The mean eradication rate for 7-day regimens of either PPI (proton pump inhibitor) or vonoprazan-sitafloxacin-amoxicillin was 80.6% (95% CI, 75.2-85.0). The vonoprazan-sitafloxacin-amoxicillin regimen was significantly superior to the PPI-sitafloxacin-amoxicillin regimen (pooled OR of successful eradication: 6.00; 95% CI: 2.25-15.98, p < 0.001). The PPI-sitafloxacin-amoxicillin regimen was comparable with PPI-sitafloxacin-metronidazole regimens (pooled OR: 1.06; 95% CI: 0.55-2.07, p = 0.86)., Conclusions: Although the 7-day regimen composed of vonoprazan, sitafloxacin, and amoxicillin is a good option as the third-line Helicobacter pylori eradication treatment in Japan, the extension of treatment duration should be considered to further improve the eradication rate. Considering the safety concern of fluoroquinolones, sitafloxcin should be used after confirming drug susceptibility.

Background: Acute decompensation (AD) of liver cirrhosis (LC) and subsequent acute-on-chronic liver failure (ACLF) are fatal and impair quality of life. Insufficient knowledge of the highly heterogeneous natural history of LC, including decompensation, re-compensation, and possible recurrent decompensation, hinders the development and application of novel therapeutics. Approximately 10%-50% of AD/ACLF is reported to be precipitated by any indeterminate (unidentifiable, cryptogenic, or unknown) acute insults; however, its clinical characteristics are unclear., Methods: We conducted a single-center observational study of 2165 consecutively admitted patients with LC from January 2012 to December 2019. A total of 466 episodes of AD/ACLF in 285 patients, including their 285 first indexed AD/ACLF, were extracted for analysis. Stratified analyses of different acute precipitants, classified as indeterminate (AD/ACLFIND), bacterial infection (AD/ACLFBAC), gastrointestinal bleeding, active alcoholism, and miscellaneous, were performed., Results: AD/ACLFIND was the leading acute precipitant (28%), followed by AD/ACLFBAC (23%). AD/ACLFIND showed better survival outcomes than AD/ACLFBAC (P = 0.03); however, hyperbilirubinemia, hyponatremia, or leukocytosis significantly and uniquely characterized subgroups of AD/ACLFIND with comparable or even worse survival outcomes than those of AD/ACLFBAC. Patients with subsequent AD/ACLF significantly tended to suffer from AD/ACLF with any organ failure in AD/ACLFIND but not in AD/ACLFBAC (P = 0.004, for trend). In competing risk analysis, patients with AD/ACLFIND were significantly more vulnerable to suffer from recurrent episodes of AD/ACLF within 180 days, compared to those triggered by other precipitants (P = 0.04)., Conclusions: AD/ACLFIND, the leading acute precipitant, also plays a role in subsequent AD/ACLF. An abruptly exacerbating, remitting, and relapsing nature of systemic inflammation underlying AD/ACLF may also be useful for risk estimation., Competing Interests: The authors have declared that no competing interests exist.

Background: Hyperplastic polyps are considered non-neoplastic, whereas sessile serrated lesions (SSLs) are precursors of cancer via the ''serrated neoplastic pathway''. The clinical features of SSLs are tumor size (> 5 mm), location in the proximal colon, coverage with abundant mucus called the ''mucus cap'', indistinct borders, and a cloud-like surface. The features in magnifying narrow-band imaging are varicose microvascular vessels and expanded crypt openings. However, accurate diagnosis is often difficult., Aim: To develop a diagnostic score system for SSLs., Methods: We retrospectively reviewed consecutive patients who underwent endoscopic resection during colonoscopy at the Toyoshima endoscopy clinic. We collected data on serrated polyps diagnosed by endoscopic or pathological examination. The significant factors for the diagnosis of SSLs were assessed using logistic regression analysis. Each item that was significant in multivariate analysis was assigned 1 point, with the sum of these points defined as the endoscopic SSL diagnosis score. The optimal cut-off value of the endoscopic SSL diagnosis score was determined by receiver-operating characteristic curve analysis., Results: Among 1288 polyps that were endoscopically removed, we analyzed 232 diagnosed as serrated polyps by endoscopic or pathological examination. In the univariate analysis, the location (proximal colon), size (> 5 mm), mucus cap, indistinct borders, cloud-like surface, and varicose microvascular vessels were significantly associated with the diagnosis of SSLs. In the multivariate analysis, size (> 5 mm; P = 0.033), mucus cap ( P = 0.005), and indistinct borders ( P = 0.033) were independently associated with the diagnosis of SSLs. Size > 5 mm, mucus cap, and indistinct borders were assigned 1 point each and the sum of these points was defined as the endoscopic SSL diagnosis score. The receiver-operating characteristic curve analysis showed an optimal cut-off score of 3, which predicted pathological SSLs with 75% sensitivity, 80% specificity, and 78.4% accuracy. The pathological SSL rate for an endoscopic SSL diagnosis score of 3 was significantly higher than that for an endoscopic SSL diagnosis score of 0, 1, or 2 ( P < 0.001)., Conclusion: Size > 5 mm, mucus cap, and indistinct borders were significant endoscopic features for the diagnosis of SSLs. Serrated polyps with these three features should be removed during colonoscopy., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background & Aims: The number of patients with non-alcoholic steatohepatitis (NASH) is increasing globally. Recently, specific chemokine receptors have garnered interest as therapeutic targets in NASH. This is the first report to examine the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine receptor ligand 25 (CCL25) axis, and to reveal its therapeutic potential in NASH., Methods: Patients with biopsy-proven non-alcoholic liver disease (NAFLD) were recruited and their serum and hepatic chemokine expression was examined. Furthermore, wild-type (WT) and Ccr9 -/- mice were fed a high-fat high-cholesterol (HFHC) diet for 24 weeks to establish NASH., Results: Serum CCL25, and hepatic CCR9 and CCL25 expression levels were increased in patients with NASH compared to healthy volunteers. Furthermore, Ccr9 -/- mice were protected from HFHC diet-induced NASH progression both serologically and histologically. Flow cytometry and immunohistochemistry analysis showed that CCR9 + CD11b + inflammatory macrophages accumulated in the inflamed livers of HFHC diet-fed mice, while the number was reduced in Ccr9 -/- mice. Consistent with human NASH livers, CCR9 was also expressed on hepatic stellate cells (HSCs) in mice with NASH, while CCR9-deficient HSCs showed less fibrogenic potential in vitro. Administration of a CCR9 antagonist hampered further fibrosis progression in mice with NASH, supporting its potential clinical application. Finally, we showed that CCR9 blockade attenuated the development of NAFLD-related hepatocellular carcinoma in HF diet-fed mice injected with diethylnitrosamine., Conclusions: These results highlight the role of the CCR9/CCL25 axis on macrophage recruitment and fibrosis formation in a murine NASH model, providing new insights into therapeutic strategies for NASH., Lay Summary: Herein, we show that a specific chemokine axis involving a receptor (CCR9) and its ligand (CCL25) contributes to the progression of non-alcoholic steatohepatitis and carcinogenesis in humans and mice. Furthermore, treatment with a CCR9 antagonist ameliorates the development of steatohepatitis and holds promise for the treatment of patients with non-alcoholic steatohepatitis., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (© 2021 S. Karger AG, Basel.)

The ABC method combined with Helicobacter pylori antibody and serum pepsinogen is a useful predictive method for stomach cancer. Kyoto classification is a new grading system for endoscopic gastritis. However, the consistency of the Kyoto score with the ABC method remains unclear. The Kyoto classification score, which ranges from 0 to 8, is based on the following findings: atrophy, intestinal metaplasia, diffuse redness, nodularity, and enlarged folds. Furthermore, we defined a simplified Kyoto classification score as the sum of scores of just atrophy and intestinal metaplasia. The association between the Kyoto classification score and the ABC method was analyzed using the Kruskal-Wallis and Steel-Dwass tests. A total of 307 subjects were enrolled. Kyoto classification scores were similar in groups B, C, and D, while scores in group A were significantly lower than those of the other groups. The simplified Kyoto classification score showed the same stepwise increase as the classification of the ABC method. In conclusion, unlike the Kyoto classification score, the simplified Kyoto score showed the same significant stepwise increase as the classification of the ABC method., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBN.)

Background: Vonoprazan has been more widely used for artificial ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer; however, no reports have examined intragastric pH during ESD. The present study aimed to measure gastric pH at the time of ESD and the clinical course afterwards for patients treated with vonoprazan the night before undergoing ESD., Materials and Methods: We examined medication status regarding gastric acid secretion and antithrombotic drugs, post-ESD bleeding as a perioperative complication, and the timing of upper gastrointestinal endoscopy after ESD and ulcer healing in 156 patients who underwent gastric ESD at our hospital from January 2014 to December 2019. The gastric pH was measured at the time of ESD after administration of 20 mg vonoprazan on the night before gastric ESD., Results: There were 14 cases of post-ESD bleeding in patients treated with proton-pump inhibitors (PPIs), including oozing during second-look endoscopy compared to only 1 case of bleeding with vonoprazan administration (p < 0.05). Vonoprazan was also associated with better post-ESD ulcer healing than PPIs. Gastric pH during ESD after vonoprazan administration on the night before gastric ESD was ≥6.96 in all 11 patients., Conclusion: Post-ESD bleeding was reduced, and ulcer healing was improved in patients treated with vonoprazan the night before their procedure. Our results suggest high gastric pH during ESD due to vonoprazan administration may be beneficial for hemostasis and ulcer healing following ESD., Competing Interests: None., (© 2020 The Authors.)

Background: We have previously reported that Helicobacter pylori ( H. pylori )-associated nodular gastritis could occur in both the antrum and the cardia. Cardiac nodularity-like appearance (hereafter, called as cardiac nodularity) had a high predictive accuracy for the diagnosis of H. pylori infection. In the previous study, we included only the patients who were evaluated for H. pylori infection for the first time, and excluded patients with a history of eradication. Therefore, the prevalence and clinical features of cardiac nodularity remains unknown., Aim: To perform this cross-sectional study to explore the characteristics of cardiac nodularity., Methods: Consecutive patients who underwent esophagogastroduodenoscopy between May, 2017 and August, 2019 in the Toyoshima Endoscopy Clinic were enrolled in this study. We included H. pylori -negative, H. pylori -positive, and H. pylori -eradicated patients, and excluded patients with unclear H. pylori status and eradication failure. H. pylori infection was diagnosed according to serum anti- H. pylori antibody and the urea breath test or histology. Cardiac nodularity was defined as a miliary nodular appearance or the presence of scattered whitish circular small colorations within 2 cm of the esophagogastric junction. Nodularity was visualized as whitish in the narrow-band imaging mode. We collected data on the patients' baseline characteristics., Results: A total of 1078 patients were finally included. Among H. pylori -negative patients, cardiac nodularity and antral nodularity were recognized in 0.14% each. Among H. pylori -positive patients, cardiac nodularity and antral nodularity were recognized in 54.5% and 29.5%, respectively. Among H. pylori -eradicated patients, cardiac nodularity and antral nodularity were recognized in 4.5% and 0.6%, respectively. The frequency of cardiac nodularity was significantly higher than that of antral nodularity in H. pylori -positive and -eradicated patients. The frequencies of cardiac nodularity and antral nodularity in H. pylori -eradicated patients were significantly lower than those in H. pylori -positive patients ( P < 0.001). The patients with cardiac nodularity were significantly younger than those without cardiac nodularity ( P = 0.0013). Intestinal metaplasia score of the patients with cardiac nodularity were significantly lower than those without cardiac nodularity ( P = 0.0216). Among H. pylori -eradicated patients, the patients with cardiac nodularity underwent eradication significantly more recently compared with those without cardiac nodularity ( P < 0.0001)., Conclusion: This report outlines the prevalence and clinical features of cardiac nodularity, and confirm its close association with active H. pylori infection., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aim: In gastroesophageal reflux disease (GERD), the additive effect of mosapride to a proton pump inhibitor (PPI) is still controversial. This meta-analysis integrated randomized controlled trials (RCTs) in which mosapride combined with a PPI was compared with a PPI alone in GERD treatment., Methods: RCTs were systematically searched with the PubMed, Cochrane library, Web of Science, and the Igaku-Chuo-Zasshi database. We combined the data from the RCTs with a random effects model, calculated the standardized mean difference (SMD) and pooled the risk difference (RD) with 95% confidence intervals (CIs)., Results: We included nine RCTs in the present meta-analysis. In the mosapride combined with PPI group, the improvement of the symptom score was significantly greater than that in the PPI alone group without significant heterogeneity (SMD: -0.28, 95% CI: -0.45 to -0.12, p = 0.0007). In the mosapride combined with PPI group, the symptom score after treatment was significantly lower than that in the PPI alone group (SMD: -0.24, 95% CI: -0.42 to -0.06, p = 0.007)., Conclusions: Mosapride combined with a PPI significantly improved the reflux symptom score compared with that of PPI alone.

Background and study aims   Helicobacter pylori -associated nodular gastritis, which is associated with follicular lymphoid hyperplasia, is mainly recognized in the antrum. However, we have also observed nodularity-like appearance in the cardia. This study aimed to investigate the clinical significance of cardiac nodularity-like appearance in H. pylori -associated gastritis. Patients and methods  Patients who underwent esophagogastroduodenoscopy and were evaluated for H. pylori infection for the first time were enrolled. A nodularity-like appearance in the cardia was defined as a miliary nodular appearance or scattered appearances of small circular whitish coloration. H. pylori infection was diagnosed according to serum anti- H. pylori antibody and the urea breath test or histology. Accuracy of the H. pylori infection diagnoses based on nodularity-like appearance were assessed. Results  Among 265 patients, 42 patients (15.8 %) were diagnosed as positive for H. pylori . Cardiac nodularity-like appearance and antral nodularity were recognized in 25 and 15 patients, respectively. In accuracy of predicting H. pylori by cardiac nodularity-like appearance, specificity was 0.996, sensitivity was 0.571, positive predictive value was 0.960, negative predictive value was 0.925, and accuracy was 0.928. The sensitivity of cardiac nodularity-like appearance was significantly higher than that of antral nodularity ( P  = 0.0284). Conclusions  Cardiac nodularity-like appearance had a high accuracy rate for H. pylori infection diagnosis. Cardiac nodularity-like appearance was found more frequently than antral nodularity., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Controversies and debates remain regarding the best management of severe acute-onset autoimmune hepatitis (SA-AIH) due to the lack of useful outcome or complication prediction systems. We conducted this clinical practice-based observational study to clarify whether Chronic Liver Failure Consortium Organ Failure scores (CLIF-C OFs) and the computed tomography-derived liver volume to standard liver volume (CTLV/SLV) ratio at admission to a tertiary transplant center can predict outcomes and complications due to infection. Thirty-four consecutive corticosteroid-treated patients with SA-AIH from 2007 to 2018 were included. Severe hepatitis was defined as an international normalized ratio (of prothrombin time) over 1.3 any time before admission. Of the 34 corticosteroid-treated patients with SA-AIH inclusive of 25 (73.5%) acute liver failure cases, transplant-free survival was observed in 24 patients (70.6%). Any infection was noticed in 10 patients (29.4%). CLIF-C OFs, at the cutoff of 9, significantly predicted survival ( P  = 0.0002, log-rank test), outperformed the Model for End-stage Liver Disease system in predicting outcome ( P  = 0.0325), and significantly discriminated between liver transplant and death in a competing risk analysis. SA-AIH was characterized as having decreased CTLV/SLV, which was also predictive of survival ( P  < 0.0001). Interestingly, CLIF-C OFs, especially the subscores for respiratory dysfunction, also predicted infection ( P  = 0.007). Conclusion: In corticosteroid-treated patients with SA-AIH, CLIF-C OFs and CTLV/SLV ratios predicted both survival outcome and complications due to infection. Further investigation is warranted to determine whether making decisions based on CLIF-C OFs or CTLV/SLV ratios is useful., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)