Published papers

Deep learning has recently been gaining attention as a promising technology to improve the identification of lesions, and deep-learning algorithms for lesion detection have been actively developed in small-bowel capsule endoscopy (SBCE). We developed a detection algorithm for abnormal findings by deep learning (convolutional neural network) the SBCE imaging data of 30 cases with abnormal findings. To enable the detection of a wide variety of abnormal findings, the training data were balanced to include all major findings identified in SBCE (bleeding, angiodysplasia, ulceration, and neoplastic lesions). To reduce the false-positive rate, “findings that may be responsible for hemorrhage” and “findings that may require therapeutic intervention” were extracted from the images of abnormal findings and added to the training dataset. For the performance evaluation, the sensitivity and the specificity were calculated using 271 detectable findings in 35 cases. The sensitivity was calculated using 68,494 images of non-abnormal findings. The sensitivity and specificity were 93.4% and 97.8%, respectively. The average number of images detected by the algorithm as having abnormal findings was 7514. We developed an image-reading support system using deep learning for SBCE and obtained a good detection performance.

Background and aim: The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods: Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results: Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion: Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication.KEY MESSAGES Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

A brief intervention is often effective for patients with mild alcohol use disorder (AUD), but it is not effective for most patients with severe AUD or alcohol dependence to reduce alcohol intake. Nalmefene (Selincro®), an opioid receptor modulator, was approved in Japan in 2019. Nalmefene was administered to 18 outpatients with alcohol-related liver diseases. Five patients stopped coming to the hospital without notice, and two patients stopped taking medicine due to dizziness. Thus, 11 patients were noted to have reduced amount of alcohol intake at 24 weeks of using nalmefene. However, one of these patients was referred to a hospital specializing in alcohol dependence thereafter. Thus, the use of nalmefene provides a new concept for AUD treatment (i. e., alcohol intake reduction). However, some adverse events are noted, such as nausea and dizziness. Therefore, physicians with more experience with AUD treatment should use the drugma.

Background and Aims: The effectiveness and durability of ustekinumab therapy with or without thiopurine immunomodulators (IMs) for ulcerative colitis (UC) in real-world Asian, Japanese patients have not yet been elucidated. Methods: To evaluate the additive effects of IMs on ustekinumab, a retrospective cohort study of UC patients receiving ustekinumab with or without thiopurine IMs, azathioprine or 6-mercaptopurine, was conducted from March 2020 to August 2021. The primary endpoint was clinical remission or response rate at week 8. The secondary endpoints were clinical remission or response rates at weeks 24 and 52, the durability of each treatment, and adverse events. Results: Of the 50 patients with UC treated with ustekinumab, 42 were enrolled. Sixteen patients were treated with a combination of ustekinumab and an IM. The clinical response rates of all patients at weeks 8, 24, and 52 were 53.7%, 63.3%, and 42.9%, respectively. There was no significant difference in the clinical responses or remission rates between the combination therapy and monotherapy groups at weeks 8, 24, and 52. (50.0% vs. 56.0%, P =. 757; 70.0% vs. 60.0%, P =. 702; and 42.9% vs. 42.9%, P = 1.00, respectively). A Kaplan-Meier analysis showed no difference in IM use on the durability of ustekinumab treatment (log-rank test; P =. 955). Conclusions: The response rate for Japanese UC patients is similar to previous reports based on American and European UC patients. There was no significant difference between the ustekinumab monotherapy group and the ustekinumab and IM combination group in the real world.

Background: Rifabutin-based regimens are used as rescue therapy for refractory Helicobacter pylori infection; however, the duration for which treatment is required and side effects are concerning. This study assessed the efficacy and safety of 7-day rifabutin, amoxicillin, and vonoprazan triple therapy as third- or later-line treatment for H. pylori infection. Materials and Methods: Patients who did not respond to second-line therapy were enrolled. After H. pylori infection was confirmed with the culture method, the patients received rifabutin-containing triple therapy (20 mg vonoprazan b.i.d., 500 mg amoxicillin q.i.d., and 150 mg rifabutin q.d.) for 7 days. Twelve weeks after the eradication therapy, successful eradication was confirmed using a 13C urea breath test or the H. pylori stool antigen test. The results obtained from our previous study that reported a 10-day or 14-day esomeprazole based rifabutin-containing triple therapy as a third- or fourth-line rescue therapy treated patients were used as historical control. We determined the minimum inhibitory concentrations of amoxicillin and rifabutin. We also evaluated whether the patients were positive for the mutation of the rpoB gene. Results: Intention-to-treat and per-protocol analyses showed that our regimen resulted in a high eradication rate (91.2%, 95% CI: 84%–99% and 92.7%, 95% CI: 86%–100%, respectively). Adverse events occurred in 31.6% of the patients, and two patients discontinued the therapy. Conclusions: This is the first study to evaluate the efficacy and safety of a 7-day low-dose rifabutin-based triple therapy with vonoprazan and amoxicillin. Our results suggest that our regimen was effective and safe as a third- or later-line H. pylori eradication regimen. To clarify what component in this regimen are critical, subsequent studies using a factorial design (comparing vonoprazan-amoxicillin dual therapy vs. vonoprazan-rifabutin triple therapy) will be needed.

Background and Aim: Oral therapeutic and invasive endoscopy requires deep sedation to reduce patient distress due to prolonged examination and procedures. The usefulness of capnography and bispectral index (BIS) monitoring in the early hypoxia detection in oral therapeutic and invasive endoscopy has yet to be evaluated. This study aimed to investigate the clinical impact of capnography and BIS monitoring on hypoxic events during oral therapeutic and invasive endoscopic procedures. Methods: This is a prospective observational study. Trans-oral non-intubated therapeutic and/or invasive endoscopic procedures were performed with conventional monitoring (pulse oximetry, pulse, and blood pressure) as well as additional monitoring (BIS and end-tidal CO2 concentration). Hypoxia is defined as oxygen saturation of <90% that lasts >15 s. The clinical impact of capnography and BIS monitoring on hypoxic events during oral therapeutic and invasive endoscopic procedures were investigated with the risk factors for hypoxia in each patient. Results: Patients with hypoxia had significantly more apneas detected using capnography than other patients. The multivariate analysis revealed the detected apnea by capnography as an independent risk factor for hypoxia (odds ratio: 3.48[95% confidence interval: 1.24–9.78], P = 0.02). The BIS was not significantly different as a risk factor for hypoxia; however, per-event analysis revealed significantly decreased BIS values over time in 3 min before hypoxic events. Conclusions: Apnea detected by capnography was an independent predictor of hypoxia. The BIS value was not associated with hypoxia events; however, it showed a significant downward trend before hypoxia events.

The endoscopic diagnosis of biliary tract lesions is applied as a non-invasive method; however, its diagnostic accuracy is not yet high. Moreover, digital cholangioscopy is used for directly visualizing the inside of the bile duct, resulting in a more precise biopsy. We present the case series of the outcomes of diagnosis using digital cholangioscopy in patients who underwent cholangioscopy for the evaluation of biliary stenosis in our department between January 2014 and March 2021. The controls were those who underwent a biopsy for biliary stenosis with conventional endoscopic retrograde cholangiopancreatography (ERCP). Background data for each case were collected, and the clinical outcomes by biopsy were evaluated, focusing on the accuracy of the diagnosis. Cholangioscopy was performed in 15 cases, while a conventional biopsy by ERCP was performed in 172 cases. Nine of 15 cases (60.0%) were diagnosed with cholangiocarcinoma. The number of specimens obtained through conventional ERCP and cholangioscopy was 2.5 ± 1.3 and 3.3 ± 1.5, respectively (p = 0.043). The diagnostic accuracy of conventional ERCP and cholangioscopy were 65.7% (113 of 172 cases) and 100%, respectively, which was significantly higher in the group with cholangioscopy. Digital cholangioscopy is useful when the diagnosis of the biliary stricture using the conventional ERCP method is difficult.

Pancreatic cancer is the most lethal solid malignancy, and the number of patients with pancreatic cancer is increasing. Systemic chemotherapies are often ineffective for such patients, and there is an urgent need for personalized medicine. Unlike other types of cancer, personalized treatments for pancreatic cancer are still in development. Consequently, pancreatic cancer is less sensitive to anticancer drugs and is often refractory to common treatments. Therefore, advances in personalized medicine for pancreatic cancer are necessary. This review examined advances in personalized medicine for pancreatic cancer, including the use of endoscopic ultrasound (EUS)-guided sampling. EUS-guided sampling is widely used for diagnosing pancreatic tumors and is expected to be applied to sampled tissues. Additionally, there has been an increase in clinical research using EUS-guided sampling. The combination of precision medicine using genomic testing and pharmacological profiles based on high-throughput drug sensitivity testing using patient-derived organoids is expected to revolutionize pancreatic cancer treatment.

Objectives: Peutz–Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease with a clinical features related to gastrointestinal (GI) hamartomatous polyposis, frequently observed in the small bowel. Balloon-assisted enteroscopy (BAE) has made non-surgical treatment of GI polyps possible. Endoscopic mucosal resection (EMR) has been performed but was associated with complications and difficulties. Recently, endoscopic ischemic polypectomy (EIP) has been developed and its usefulness reported. The study evaluated the feasibility and safety of EIP and the clinical outcomes of patients with PJS. Methods: We retrospectively collected data of consecutive patients with PJS between September 2009 and March 2021. Data regarding clinical characteristics, follow-up methods, endoscopic management, and complications were collected. EIP feasibility and safety were assessed. Results: Twenty-two patients were included. The observation period was 70 months (range, 5–153). Of the 124 therapeutic endoscopy procedures performed, 68 used BAE. Of the 607 polyps treated, 329 polyps were located in the small bowel. EIP was able to treat a greater number of polyps per patient than EMR (P < 0.003), without any complications, carcinoma, or intussusception in the small bowel (P < 0.001). During the follow-up period, 3 patients developed GI cancer. Conclusion: Long-term follow-up in patients with PJS showed that EIP was a feasible and safe technique.

BACKGROUND: Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. OBJECTIVE: To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. METHODS: We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. RESULTS: IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. CONCLUSIONS: Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

症例は63歳男性で、2年前より自然軽快する水様性下痢を繰り返していたが、2週間前からの血性下痢が軽快せず発熱や食事摂取困難を伴ったため入院した。血液検査では炎症反応上昇、低栄養、低Ig血症を認め、下部消化管内視鏡(CS)では全大腸に渡り粘稠度の高い白苔が付着した不整形潰瘍を全周性に認め、遠位結腸は一部正常粘膜が介在し回腸末端は異常を認めなかった。入院第5病日に生検検体および便塗抹検査にてアメーバ原虫を検出し、アメーバ性大腸炎と診断した。メトロニダゾールを10日間、その後パロモマイシンを7日間投与し、入院第17病日に退院した。退院3ヵ月後のCSで潰瘍は消失したが脾彎曲に小潰瘍を伴った浮腫性狭窄が残存し、退院9ヵ月後のCSでは狭窄部以外の全大腸の治癒を確認した。狭窄箇所の生検からはアメーバ原虫は検出されなかった。

アルコール関連肝疾患患者がアルコール依存症に至っている場合,簡易介入のみでは飲酒量の低減に結び付かないケースが多い.セリンクロ錠(一般名:ナルメフェン)は,飲酒欲求を抑え飲酒量を低減させる新しい薬剤である.今回,内科外来でセリンクロ錠を処方した症例を検討し,その有用性を検討した.初回投与から24週以上経過した症例は18例で,2例はめまいのため中止し,5例は連絡なく通院を中断したため,結果として副作用もなく通院を継続し24週での評価ができた症例は11例であった.全例で飲酒量の低減と肝機能の改善を認めたが,1例はその後再度飲酒量が増え,専門医療機関に紹介入院となった.セリンクロ錠による飲酒量低減が認められ,内科外来における飲酒量低減治療の新たな選択肢となることが示唆された.一方で,中断例も認められ,めまいや嘔吐などの副作用が多いことが報告されており,十分に研修を積んだ医師が処方すべきと考えられる.(著者抄録)

症例は87歳男性。検診で増大する肝腫瘤を指摘され当科紹介受診となった。画像所見から肝内胆管癌を含む肝原発悪性腫瘍が疑われたが、胆管浸潤を示唆する所見はなく、高齢で基礎疾患を多数有するため、ラジオ波焼灼療法(RFA:radiofrequency ablation)を行なった。治療時に施行した腫瘍生検の結果、肝内胆管癌と診断されたが、同時に採取された背景肝に1930-50年にかけて使用された造影剤であるトロトラストの沈着が疑われた。再発病変に対して2度RFAを施行し、初回治療後約3年間病勢が制御されている。今回我々は、RFAにより良好な病勢制御が得られたトロトラスト沈着症による肝内胆管癌の一例を経験した。トロトラスト晩発障害による発癌症例は肝内多中心性の発癌様式を示すため、本症例のように高齢で耐術能の低い胆管細胞癌症例においては、RFAなどの局所療法が有用な治療選択肢となりうると考えられた。(著者抄録)

Objective To further disseminate the nomenclature of chronic enteropathy associated with SLCO2A1 (CEAS), especially for physicians in China and Korea where the genetic feature of SLCO2A1 gene mutations related hypertrophic osteoarthropathy and pachydermia had been extensively studied. SLCO2A1 gene mutations related hypertrophic osteoarthropathy and pachydermia had been extensively studied. Design A case report with literature review of SLCO2A1 gene mutations-related disorders. Results A 38-year-old Korean presented to a tertiary hospital with dizziness, abdominal pain and melena. He had a positive faecal occult blood test on initial workup. Oesophagogastroduodenal endoscopy (OGD), colonoscopy and CT scan were unremarkable and showed no obvious cause for his melena. Capsule endoscope and roentgen barium studies were performed, revealing an erythematous mucosa with ulcers in the jejunum and stenosis to the jejunal-ileal junction. Next-generation sequencing was then performed and discovered point mutations of SLCO2A1 gene's seven exon (940+1 G>A) and 13 exon (1807 C>T) allele. This Korean patient with CEAS is the first documented case noted outside of the Japanese population. Conclusion CEAS is not uniquely found in Japanese individuals. There are lots of similarities between CEAS and primary hypertrophic osteoarthropathy, the two entity may just be the two sides of one same coin. International and multidisciplined efforts are required to further study this complicated disorder.

An incorrect version of S2 File was published in error. This article was republished on April 2, 2019 to correct for this error. Please download this article again to view the correct version.

In the original article, the numbers on the vertical axis of Figure 1A were accidentally increased 1000-fold. The legend on the vertical axis of Figure 2B was also originally given as LRG(μ g/ml), instead of CRP(mg/dl). These errors have now been corrected in the online version of the article. The Publisher apologizes for the errors.