DIGESTION

Endoscopic resection for colorectal tumors
Hirai Y, Toyoshima N and Saito Y
Endoscopic resection techniques for colorectal tumors are constantly evolving with improvements.
Effects of a protease inhibitor camostat mesilate on gut microbial function in patients with irritable bowel syndrome: A pilot randomized placebo-controlled study
Kanazawa M, Miyamoto K, Kano M, Inooka K, Oka K, Takahashi M, Mano N and Fukudo S
Increased fecal protease activity which may induce visceral hypersensitivity has been observed in patients with irritable bowel syndrome (IBS). Serine proteases modulate FK506 binding protein (FKBP)-type peptidylprolyl cis-trans isomerase (PPIase) activity associated with immune and glucocorticoid receptor functions. The aims were to investigate whether camostat mesilate (CM), a serine protease inhibitor, modifies fecal bacterial function associated with FKBP-type PPIases ameliorates in patients with IBS.
DYRK2 regulates epithelial-mesenchymal transition restriction in pancreatic cancer liver metastasis by inhibiting Twist
Pan H, Liu Y, Bao K, Wang Y, Zhang Y and Zhou L
To explore the underlying variables and molecular pathways leading to pancreatic cancer liver metastasis.
Surveillance after endoscopic resection for colorectal tumors: a comprehensive review
Hotta K, Matsuda T, Sano Y, Fujii T and Saito Y
The goal of surveillance after the endoscopic resection of colorectal tumors is to reduce colorectal cancer (CRC) incidence and mortality. Considering the effective use of the limited endoscopic capacity and the cost of surveillance, it is desirable to develop a surveillance program that is as minimal as possible. In Europe (European Society of Gastrointestinal Endoscopy (ESGE)) and the United States (US) (Multi-Society Task Force (MSTF)), after the results of the National Polyp Study (NPS) were established, guidelines were developed that stratified risk based on initial endoscopy, and surveillance programs for each risk group were proposed. More than 10 years later, the "colonoscopy screening and surveillance guidelines" were developed with the basic principle of "aiming for zero colorectal cancer deaths during surveillance, bowel preservation, and emphasis on patient quality of life" as the guideline principles in Japan.
Estimation of invasion depth of early colorectal cancer using Endoscopic ultrasonography and Magnifying chromoendoscopy: a meta-analysis
Chen R, Huang Y and Liu F
Introduction magnifying chromoendoscopy (MCE) and Endoscopic ultrasonograpty (EUS) are often used as diagnostic tools to estimate the depth of invasion in early colorectal cancers (CRCs). The aim of this study was to compare MCE with EUS in distinguishing between slight submucosal invasion (invasion depth <1000μm) and massively submucosal invasion in patients with early CRCs, since slight submucosal invasion is currently considered as an indication for endoscopic resection and submucosal cancer with massively submucosal invasion should be surgically treated due to an increased risk of lymph node metastasis. Methods For this meta-analysis, relevant studies were identified from PubMed, Embase and the Cochrane Library databases between the time of the establishment and April 2023.Data on the yield of tumors were extracted, pooled, and analyzed by stata15.0 software. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio in differentiating massive submucosal invasion from slight submucosal invasion were calculated for both diagnostic modalities. Results Twenty-six studies involving 1,2586 lesions were included: sixteen were studies on MCE and 7 were studies on EUS and 3 were studies on both MCE and EUS. The pooled sensitivity of MCE was 0.78(95%CI 0.72-0.83), the specificity was 0.95(0.95%CI 0.91-0.97), the positive likelihood ratio was 15.4(0.95%CI 8.7-27.4) and the negative likelihood ratio was 0.23(0.95%CI 0.18-0.30).The pooled sensitivity of EUS was 0.88(95%CI 0.81-0.93), the specificity was 0.87(0.95%CI 0.80-0.91), the positive likelihood ratio was 6.7(0.95%CI 4.4-10.3) and the negative likelihood ratio was 0.13(0.95%CI 0.08-0.23). Conclusion The sensitivity tended to be higher in EUS than MCE for early CRCs with massively submucosal invasion, whereas the specificity was significantly lower in EUS than in MCE.
The Link between Metabolic Syndrome and the Brain
Zouridis S, Nasir AB, Aspichueta P and Syn WK
Metabolic syndrome (MetS) is a cluster of cardiometabolic conditions that has been linked to high risk for cardiovascular disease, liver complications, and several malignancies. More recently, MetS has been associated with cognitive dysfunction.
Urgent Contrast-Enhanced Computed Tomography before Early Colonoscopy in the Management of Colonic Diverticular Bleeding: A Multicenter Randomized Controlled Trial
Hirai Y, Uraoka T, Wada M, Mori H, Fujimoto A, Sakakibara Y, Toyokawa T, Kagaya T, Sasaki Y, Mannami T, Kuwai T, Watanabe N, Hamada H, Esaka N, Kimura T, Fujii H, Hosoda Y, Shimada M, Miyabayashi H, Somada S, Mabe K, Inoue S, Saito H, Furuya K, Kawamura N, Kudo T, Hori K, Sakamoto N, Kato M, Higuchi N, Harada N and
Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 h of arrival) or other clinical outcomes of CDB.
Screening Colonoscopy to Reduce the Incidence and Mortality of Colorectal Cancer
Tada N, Tamai N and Sumiyama K
Colorectal cancer (CRC) is a major concern because of its increasing incidence and mortality worldwide. Therefore, effective screening strategies are necessary to reduce its incidence.
Implementation of machine learning algorithms to screen for advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD): an in-depth explanatory analysis
Dabbah S, Mishani I, Davidov Y and Ben Ari Z
Background This study aimed to train machine learning algorithms(MLAs) to detect advanced fibrosis(AF) in MASLD patients at the level of primary care setting and to explain the predictions to ensure responsible use by clinicians. Methods Readily available features of 618 MASLD patients followed up at a tertiary center were used to train five MLAs. AF was defined as liver stiffness≥9.3 kPa, measured via 2-dimension shear wave elastography(n=495) or liver biopsy≥F3(n=123). MLAs were compared to Fibrosis-4 index(FIB-4) and NAFLD fibrosis score(NFS) on 540 MASLD patients from the primary care setting as validation. Feature importance, partial dependence, and shapely additive explanations(SHAP) were utilized for explanation. Results Extreme gradient boosting(XGBoost) achieved an AUC=0.91,outperforming FIB-4(AUC=0.78) and NFS(AUC=0.81, both p<0.05) with specificity=76% vs. 59% and 48% for FIB-4≥1.3 and NFS≥-1.45, respectively(p<0.05). Its sensitivity(91%) was superior to FIB-4(79%). XGBoost confidently excluded AF (negative predictive value=99%) with the highest positive predictive value (31%), superior to FIB-4 and NFS (all p<0.05). The most important features were HbA1c and GGT with a steep increase in AF probability at HbA1c>6.5%. The strongest interaction was between AST and age. XGBoost, but not logistic regression, extracted informative patterns from ALT, LDL-c,and ALP(p<0.001). One quarter of the false positives (FP) were correctly reclassified with only one additional false negative based on the SHAP values of GGT, platelets, and ALT which were found to be associated with a FP classification. Conclusions: An explainable XGBoost algorithm was demonstrated superior to FIB-4 and NFS for screening of AF in MASLD patients at the primary care setting. The algorithm also proved safe for use as clinicians can understand the predictions and flag FP classifications.
Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review
Chu P, Mioc J, O'Donovan P and Henry O
Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI.
Artificial Intelligence for Contrast-Enhanced Ultrasound of the Liver: A Systematic Review
Brooks JA, Kallenbach M, Radu IP, Berzigotti A, Dietrich CF, Kather JN, Luedde T and Seraphin TP
The research field of artificial intelligence (AI) in medicine and especially in gastroenterology is rapidly progressing with the first AI tools entering routine clinical practice, for example, in colorectal cancer screening. Contrast-enhanced ultrasound (CEUS) is a highly reliable, low-risk, and low-cost diagnostic modality for the examination of the liver. However, doctors need many years of training and experience to master this technique and, despite all efforts to standardize CEUS, it is often believed to contain significant interrater variability. As has been shown for endoscopy, AI holds promise to support examiners at all training levels in their decision-making and efficiency.
NEIL3 Upregulated by TFAP2A Promotes M2 Polarization of Macrophages in Liver Cancer via the Mediation of Glutamine Metabolism
Zhang F, Wang B, Zhang W, Xu Y, Zhang C and Xue X
Tumor-associated macrophages, which are part of the tumor microenvironment, are a major factor in cancer progression. However, a complete understanding of the regulatory mechanism of M2 polarization of macrophages (Mø) in liver cancer is yet to be established. This study aimed to investigate the potential mechanism by which NEIL3 influenced M2 Mø polarization in liver cancer.
C-Kit Immunohistochemical Expression as a Complementary Method to Assess Mast Cell Density in Helicobacter pylori-Mediated Gastritis
Ismael AT, Abdulhameed RA, Hamdi BA, Tawfeeq RD and Ommar A
Chronic gastritis is a group of conditions commonly characterized by stomach lining inflammation. The study aimed to investigate the clinical and pathological aspects that play a role in its development. Additionally, the study examines the use of CD117 as an immunohistochemistry marker in evaluating mast cell density (MCD).
Efficacy and Safety of Etrasimod in Patients with Ulcerative Colitis in Japan: Data from the Phase 3 ELEVATE UC 12 and ELEVATE UC 40 JAPAN Trials
Takeuchi K, Hisamatsu T, Nakase H, Matsuoka K, Keating M, Yuasa H, Oe M, Arai S, Mazur R and Hibi T
Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the primary analysis of a phase 3 trial evaluating the efficacy and safety of etrasimod in patients from Japan with moderately to severely active UC.
Management of T1 Colorectal Cancer
Tanaka H, Yamashita K, Urabe Y, Kuwai T and Oka S
Approximately 10% of patients with submucosal invasive (T1) colorectal cancer (CRC) have lymph node metastasis (LNM). The risk of LNM can be stratified according to various histopathological factors, such as invasion depth, lymphovascular invasion, histological grade, and tumor budding.
Toll-Like Receptor 7-Expressed Macrophages Are Involved in the Pathogenesis of Esophageal Achalasia and Esophagogastric Junction Outflow Obstruction
Kaizuka M, Tatsuta T, Kawaguchi S, Yoshizawa T, Yoshida S, Tateda T, Sawada Y, Ota S, Hayamizu S, Hasui K, Kikuchi H, Hiraga H, Chinda D, Muroya T, Hakamada K, Kijima H, Mikami T, Fukuda S and Sakuraba H
Esophageal achalasia is a typical esophageal motility disorder (EMD). Although viral infections have been hypothesized to play a role in the pathogenesis of esophageal achalasia, its etiology remains unclear. This study used esophageal muscle layer specimens collected during per-oral endoscopic myotomy (POEM) procedures to investigate the association between esophageal achalasia and esophagogastric junction outflow obstruction (EGJOO) and pattern recognition receptors.
Evidence-Based Clinical Guidelines for Chronic Constipation 2023
Ihara E, Manabe N, Ohkubo H, Ogasawara N, Ogino H, Kakimoto K, Kanazawa M, Kawahara H, Kusano C, Kuribayashi S, Sawada A, Takagi T, Takano S, Tomita T, Noake T, Hojo M, Hokari R, Masaoka T, Machida T, Misawa N, Mishima Y, Yajima H, Yamamoto S, Yamawaki H, Abe T, Araki Y, Kasugai K, Kamiya T, Torii A, Nakajima A, Nakada K, Fukudo S, Fujiwara Y, Miwa H, Kataoka H, Nagahara A and Higuchi K
The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide.
Erratum
Identification of a Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis
Dong S, Zhang Y, Ye L and Cao Q
Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.
Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023
Ihara E, Manabe N, Ohkubo H, Ogasawara N, Ogino H, Kakimoto K, Kanazawa M, Kawahara H, Kusano C, Kuribayashi S, Sawada A, Takagi T, Takano S, Tomita T, Noake T, Hojo M, Hokari R, Masaoka T, Machida T, Misawa N, Mishima Y, Yajima H, Yamamoto S, Yamawaki H, Abe T, Araki Y, Kasugai K, Kamiya T, Torii A, Nakajima A, Nakada K, Fukudo S, Fujiwara Y, Miwa H, Kataoka H, Nagahara A and Higuchi K
The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and anti-diarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogs, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.
Efficacy of Donor-Recipient-Matched Faecal Microbiota Transplantation in Patients with IBS-D: A Single-Centre, Randomized, Double-Blind Placebo-Controlled Study
Zhang Y, Wang S, Wang H, Cao M, Wang M, Zhang B, Xiao C, Zhu H and Du S
The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualized treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient-matched FMT in IBS with predominant diarrhoea (IBS-D) and evaluate its effects on gut microbiota.