Published papers

Background: Moderate alcohol consumption is believed to be associated with reduced mortality from cardiovascular disease (CVD) in the general population. This cross-sectional study aimed to comprehensively examine the association between alcohol consumption and subclinical cardiovascular damage or hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: Subjects with NAFLD without a history of heart disease were extracted from 977 consecutive examinees who completed health checkups and optional cardiovascular examinations. Subclinical cardiovascular damage was assessed by coronary artery calcification (CAC), carotid artery ultrasound, and brachial-ankle pulse wave velocity (ba-PWV). CAC scores were classified into three grades (0, ≤100, and >100) by Agatston's method. Alcohol consumption was divided into three groups [Non-drinking (G0); Light (G1), 0.1–6.9 drinks/week; Moderate (G2), 7–20.9 drinks/week for men and 7–13.9 drinks/week for women]. Noninvasive markers (FIB-4, Fibrosis-4; NFS, NAFLD fibrosis score) were calculated for assessment of hepatic fibrosis and classified into low and intermediate-high grade. Results: The overall mean age was 60.2 years and males were 200 (74.6%) among 268 subjects with NAFLD. Number (%) of G0, G1, and G2 were 102 (38.1%), 103 (38.4%), and 63 (23.5%). Binary logistic regression analysis showed no significant difference between G0 and G1, or G0 and G2 in any of the above subclinical cardiovascular damages (CAC score >0, or CAC score >100, carotid plaque +, intima-media thickness ≥1.1 mm, and ba-PWV >1400 cm/s). However, only G2 had a significant association with intermediate-high grade of FIB-4 or NFS [odds ratio (95% confidence intervals), p value: 1.871 (1.209–2.893), p = 0.005; 2.910 (1.715–4.939), p = 0.000], compared to G0. Conclusions: Non-heavy drinking might not reduce the risk of CVD in NAFLD subjects. On the contrary, even moderate drinking could promote hepatic fibrosis. Thus, NAFLD drinkers should not be recommended for even a moderate amount of alcohol.

Background and Aim: 5-Aminosalicylic acid (5-ASA) is a fundamental treatment for mild-to-moderate ulcerative colitis (UC). 5-ASA is taken up into the colonic mucosa and metabolized to N-acetyl-5-ASA (Ac-5-ASA). Few studies have assessed whether mucosal 5-ASA and Ac-5-ASA concentrations are associated with endoscopic remission. This study aimed to investigate differences in 5-ASA and Ac-5-ASA concentrations according to endoscopic activity. Methods: This single-center, prospective, cross-sectional study was conducted between March 2018 and February 2019. UC patients who were administered with 5-ASA medication for at least 8 weeks before sigmoidoscopy were enrolled. Mucosal 5-ASA and Ac-5-ASA concentrations were measured using liquid chromatography with tandem mass spectrometry. The primary endpoint was defined as the difference in mucosal concentrations of 5-ASA and Ac-5-ASA, according to the Mayo endoscopic subscore (MES). Results: Mucosal concentrations were analyzed in 50 patients. In the sigmoid colon, the median 5-ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥ 1 (6.4 ng/mg) (P = 0.019). The median 5-ASA concentrations in patients with Ulcerative Colitis Endoscopic Index of Severity ≤ 1 (16.4 ng/mg) were also significantly higher than in patients with Ulcerative Colitis Endoscopic Index of Severity ≥ 2 (4.63 ng/mg) (P = 0.047). In the sigmoid colon, the concentration of Ac-5-ASA was higher in patients with MES of 0 (21.2 ng/mg) than in patients with MES ≥ 1 (5.81 ng/mg) (P = 0.022). Conclusions: The present study showed that mucosal Ac-5-ASA concentrations, as well as 5-ASA concentrations, are higher in UC patients with endoscopic remission. Ac-5-ASA may be useful for a biomarker of 5-ASA efficacy.

Purpose: Immune checkpoint inhibitors (ICIs) have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in real-world practice. Patients and Methods: We conducted a retrospective study on patients with recurrent or metastatic non-small-cell lung cancer, malignant melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model and the shared frailty model. Results: Of 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. The median OS was significantly longer in the irAEs than in the no-irAE group (28.1 months vs 12.7 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33–0.73; P = 0.0004). Moreover, the OS of patients with multiple irAEs was significantly longer than that of patients with a single irAE (42.3 months vs 18.8 months; HR, 0.473; 95% CI, 0.346–0.647; P < 0.0001). Conclusion: Our single-center retrospective study revealed a significant tendency associating the development of multiple irAEs with favorable prognoses.

© 2018 Hsieh et al. Since anti-tumor necrosis factor (TNF)-α agents (TNF-α inhibitors) induce both clinical response and remission in patients with moderate to severe inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally changed the approach to treatment for patients with IBD. Infliximab (IFX) is a TNF-α inhibitor approved for the induction and remission of Crohn's disease (CD). However, even among patients who initially demonstrate a clinical response to IFX therapy, secondary loss of response occurs, although the reason remains unknown. We therefore investigated predictive factors associated with the response to IFX in long-term maintenance treatment in Japanese CD patients. Eight types of single-nucleotide polymorphisms (SNPs) were investigated using the real-time PCR method, and patient characteristics were collected from the electronic medical records. The Crohn's Disease Activity Index criteria were used as the response to IFX therapy. The observation period was 1 year after IFX had been administered for more than 1 year. Associations between the IFX response and patient characteristics were evaluated using the multivariate logistic regression model. We studied 121 unrelated adult Japanese with CD treated for more than 1 year with IFX as outpatients at Keio University Hospital from November 1, 2014 to November 30, 2015. Among them, 71 were classified as in remisson. In multivariate analysis, patients with the TNF-α 857C>T C/C genotype, shorter disease duration, without double dosing, and combination treatment with an immunomodulator had higher remisson rates than those with the C/T or T/T genotype, longer disease duration, with double dosing, and no combination treatment with an immunomodulator. The response to IFX in Japanese CD patients may therefore be predicted by these 4 characteristics in actual clinical practice.

© 2018 Crohn's & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions. Background Mucosal healing (MH) is proposed as a therapeutic target for ulcerative colitis (UC). Recent studies have indicated that the rate of clinical relapse in patients with a Mayo endoscopic score (MES) of 1 is higher than that of patients with an MES of 0. However, no study has yet investigated whether therapeutic intervention prevents clinical relapse in patients with an MES of 1. Methods Patients with UC with an MES of 1 and partial Mayo score ≤2 were included in this study. All patients were followed from first colonoscopy (CS) until follow-up CS. Differences in the rate of clinical relapse (requiring additional treatment for UC) or endoscopic exacerbation (MES ≥2 and proximal extension) were compared between the therapeutic intervention (immediately after first CS) group and the nontherapeutic intervention group; risk factors for relapse were also assessed. Results Among 1523 patients with UC who underwent CS between 2013 and 2016, 220 patients were included in this study. The rate of clinical relapse (P = 0.005) and endoscopic exacerbation (P = 0.11) in patients with therapeutic intervention was lower than that in patients without therapeutic intervention. Multivariable analysis indicated that absence of therapeutic intervention (P = 0.001 for clinical relapse, P = 0.050 for endoscopic exacerbation) and a higher Ulcerative Colitis Endoscopic Index of Severity vascular pattern score immediately after first CS (P = 0.021 for clinical relapse, P = 0.019 for endoscopic exacerbation) were risk factors for both clinical relapse and endoscopic exacerbation. Conclusions Therapeutic intervention for patients with UC with an MES of 1 might prevent disease relapse.

© 2018 Elsevier Inc. Recent sequencing analyses have shed light on heterogeneous patterns of genomic aberrations in human gastric cancers (GCs). To explore how individual genetic events translate into cancer phenotypes, we established a biological library consisting of genetically engineered gastric organoids carrying various GC mutations and 37 patient-derived organoid lines, including rare genomically stable GCs. Phenotype analyses of GC organoids revealed divergent genetic and epigenetic routes to gain Wnt and R-spondin niche independency. An unbiased phenotype-based genetic screening identified a significant association between CDH1/TP53 compound mutations and the R-spondin independency that was functionally validated by CRISPR-based knockout. Xenografting of GC organoids further established the feasibility of Wnt-targeting therapy for Wnt-dependent GCs. Our results collectively demonstrate that multifaceted genetic abnormalities render human GCs independent of the stem cell niche and highlight the validity of the genotype-phenotype screening strategy in gaining deeper understanding of human cancers. Generation and analysis of a human gastric cancer organoid bank reveal insights into molecular features underlying diverse histopathological subtypes and tumor independence from Wnt signals.

© 2018 The Author(s). Background: We previously showed that knockdown of nuclear factor E2-related factor 2 (Nrf2) resulted in suppression of hepatitis C virus (HCV) infection. In this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer effects was explored. Methods: The anti-HCV effect of brusatol was investigated by analyzing HCV RNA and proteins in a hepatic cell line persistently-infected with HCV, HPI cells, and by analyzing HCV replication in a replicon-replicating hepatic cell line, OR6 cells. Then, dual anti-HCV and anticancer effects of brusatol and enhancement of the effects by the combination of brusatol with anticancer drugs including sorafenib, which has been reported to have the dual effects, were then investigated. Results: Brusatol suppressed the persistent HCV infection at both the RNA and protein levels in association with a reduction in Nrf2 protein in the HPI cells. Analysis of the OR6 cells treated with brusatol indicated that brusatol inhibited HCV persistence by inhibiting HCV replication. Combination of brusatol with an anticancer drug not only enhanced the anticancer effect but also, in the case of the combination with sorafenib, strongly suppressed HCV infection. Conclusions: Brusatol has dual anti-HCV and anticancer effects and can enhance the comparable effects of sorafenib. There is therefore the potential for combination therapy of brusatol and sorafenib for HCV-related hepatocellular carcinoma.

© 2018 Crohn's & Colitis Foundation. Published by Oxford University Press. All rights reserved. Background: The usefulness of second-generation colon capsule endoscopy (CCE-2) for ulcerative colitis (UC) has not been fully demonstrated. This study aimed to develop an endoscopic severity score of UC for CCE-2. Methods: Patients diagnosed with UC were enrolled prospectively and underwent colonoscopy and CCE-2 on the same day. The collected CCE-2 videos were adopted for the development of the score. These videos were scored by 4 blinded inflammatory bowel disease experts. The items validated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were used as the candidate items, some of which were automatically assessed using the workstation. Each item was divided into proximal and distal parts at the splenic flexure and then individually assessed. The image readers simultaneously evaluated the inflammation severity using the visual analog scale (VAS). The descriptors that contribute to this scale were evaluated, and a model to predict the VAS was constructed. The UCEIS was scored by other endoscopists using colonoscopy videos. The correlation coefficients with fecal calprotectin, blood tests, and Lichtiger index were calculated. Results: The final scoring system was fixed as "vascular pattern sum (proximal + distal) + bleeding sum + erosions and ulcers sum (minimum- maximum, 0-14)" and was named Capsule Scoring of Ulcerative Colitis (CSUC). The correlation coefficient of CSUC with biomarkers and clinical score was similar to that of the UCEIS. Conclusions: We developed a new simple score using the 3 descriptors of CCE-2.

© 2018, The Author(s). Background: Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients. Aims: To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC. Methods: This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC). Results: An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63–2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient). Conclusions: BFM had no effect on time to relapse in UC patients compared with placebo. Study Registration: UMIN000007593.

© 2018. Korean Association for the Study of Intestinal Diseases. Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.

© 2018 AGA Institute Background & Aims: Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. Methods: We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0–1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. Results: The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P <.0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P =.0004) and the 2.0 g IN group (38.1%, (P =.0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P =.0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. Conclusions: In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5–2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).

© 2018 American Society for Gastrointestinal Endoscopy Background and Aims: We developed a suturing method with string and clips for a single-channel endoscope. The feasibility of the string clip suturing method is evaluated in this prospective pilot study. Methods: This study involved 10 consecutive patients who underwent endoscopic submucosal dissection (ESD) for a duodenal tumor. Polyester string was tied to the arm of a partially out thrust clip. The clip and string can be passed through the instrument channel (3.2 mm) of a single-channel endoscope. The clip with string was placed at the distal edge of the large mucosal defect. A second clip was hooked on the string and placed on the opposite side. Both clips were gathered by pulling the free end of the string, and additional clips were placed to achieve complete closure. This method was compared with that for the previous 10 patients without mucosal closure after duodenal ESD. Results: Mean size of resected specimens was 39.1 ± 12.4 mm. The success rate of the string clip suturing method was 100% (10/10). The mean procedure time was 23.4 ± 13.8 minutes. Perforation during ESD occurred in 1 patient and was successfully closed by this method. None of the treated patients developed serious adverse events after the procedure. Compared with the no-suture group, the length of stay was significantly shorter (P =.038). Conclusion: The string clip suturing method appears to be a safe and effective method for closure of large mucosal defects. (Clinical trial registration number: UMIN000023698.)

© 2019, Korean Association for the Study of Intestinal Diseases. All rights reserved. Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto-severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.

© 2019 S. Karger AG, Basel. All rights reserved. Background: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. Objectives: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. Method: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. Results: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. Conclusions: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.

© 2019 Editrice Gastroenterologica Italiana S.r.l. Background: Although various studies have been conducted on colitis-associated cancer (CAC), few have assessed the differences in the clinical and endoscopic features, treatment, and prognosis of CAC and sporadic neoplasia (SN) in the inflamed mucosa of ulcerative colitis (UC) patients. Aims: To compare the characteristics of CAC and SN within the previously or currently inflamed mucosa. Methods: Between 1997 and 2017, we retrospectively analyzed the endoscopic chart data of 348 colonic lesions from 266 UC patients. Non-dysplastic lesions and lesions located outside the inflamed mucosa were excluded. The diagnosis of CAC or SN was confirmed by conventional histopathological and immunohistochemical evaluation of p53 and Ki67. Results: In total, 74 patients with CAC (97 lesions) and 46 with SN (58) were enrolled. The proportions of patients with a younger age of onset of UC, with chronic persistent UC, and with severe inflamed mucosa were significantly higher in the CAC group. In the SN group, no flat lesions were found, whereas 26% of the lesions in the CAC group were flat. Sixteen patients died during a median follow-up of 6.1 years (interquartile range (IQR) 1.8–11.1)in the CAC group, whereas 1 patient died during a median follow-up 3.2 years(IQR 1.4–4.6) in the SN group. Mortality from colorectal cancer was significantly higher (P = 0.015) in the CAC group (12/68; 17.6%) than in the SN group (1/44; 2.3%). The 5-year survival rate was 100% in the SN group and 97% in the CAC group for lesions located in the mucosa or submucosa. Conclusion: Recognizing differences in the characteristics of CAC and SN within the inflamed mucosa is critical to avoid unnecessary total colectomy in patients with SN.

© 2018, The Author(s). Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of patients with PSC and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper 17 (T H 17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to T H 17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the T H 17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.

© 2019 The Japanese Society of Internal Medicine. Objective Risks of bleeding and pancreatitis after mucosal resection using the purecut/autocut and blendcut/ endocut modes for endoscopic papillectomy have not been fully clarified. Thus, a systematic review on electrosurgical cutting modes for endoscopic papillectomy was conducted focusing on the types and incidence of adverse events. Methods We searched the PubMed and Cochrane library for cases of endoscopic papillectomy recorded as of April 2017. Studies reporting the methods of electrically excising a tumor in the duodenal papilla and the number of adverse events were extracted. Studies were collected and examined separately based on the electrosurgical cutting mode, and the incidence rate for each adverse event was summarized. Results A total of 159 relevant articles were found; among them, 20 studies were included and 139 excluded. Five studies analyzed endoscopic papillectomy with the purecut/autocut mode and 16 with the blendcut/ endocut mode. Only one study investigated both modes (purecut and endocut). With the purecut/autocut mode, the incidence of bleeding was 2.8-50%, and that of pancreatitis was 0-50% (mean: 12.8%). With the blendcut/endocut mode, the incidence of bleeding was 0-42.3%, and that of pancreatitis was 0%-17.9% (mean: 9.5%). Conclusion Both methods had high adverse event rates for endoscopic papillectomy. Thus, a standard method of endoscopic papillectomy, including the electrosurgical cutting mode, needs to be established.

© 2019 Japan Gastroenterological Endoscopy Society Background and Aim: Underwater endoscopic mucosal resection (UEMR) has been reported as an alternative to conventional EMR for superficial non-ampullary duodenal epithelial tumors (SNADET). However, the detailed outcomes are unclear. This study aimed to compare the clinical outcomes between UEMR and EMR for SNADET <20 mm. Patients and methods: This is a retrospective observational study using a prospective maintained database. From November 2017 to December 2018, 104 consecutive cases of attempted UEMR for SNADET <20 mm were prospectively allocated. A total of 240 cases of attempted EMR were chosen as historical controls. We compared technical success rate, defined as the resection rate without conversion to ESD; en bloc resection rate; R0 resection rate; and adverse event rate. Next, multivariate analyses were constructed to identify predictors of conversion to ESD, piecemeal resection, and RX or R1 (RX/R1) resection. Results: Technical success rate of UEMR was significantly higher than that of EMR (87% and 70%, P < 0.01). En bloc resection and R0 resection rates of UEMR were significantly lower than those of EMR (en bloc resection: 87% vs 96%, P < 0.01; R0 resection: 67% vs 80%, P = 0.05). Concerning adverse events, there were no significant differences. In multivariate analyses, attempted EMR, lesion size and depressed type were independent predictors of conversion to ESD. Attempted UEMR was an independent predictor of piecemeal resection and RX/R1 resection. Conclusion: The present study indicated that UEMR could be a feasible endoscopic resection method for SNADET (UMIN000025442).

© 2018 The Author(s) This study describes a patient who experienced hepatobiliary Mycobacterium avium infection associated with neutralizing anti–interferon gamma (IFN-γ) autoantibodies during treatment for disseminated M. avium disease. Hepatobiliary M. avium infection should be considered in jaundiced patients with neutralizing anti–IFN-γ autoantibodies, including those receiving antimycobacterial therapy for disseminated M. avium disease.