Digestion[JOURNAL]
Sun
200 papers
Deep Learning-Based Detection of Malignant Bile Duct Stenosis in Fluoroscopy Images of Endoscopic Retrograde Cholangiopancreatography.
Vu Trung K, Hollenbach M, Veldhuizen GP … +10 more , Saldanha OL, Garbe J, Rosendahl J, Krug S, Michl P, Feisthammel J, Karlas T, Hampe J, Hoffmeister A, Kather JN
Digestion · 2025 · PMID 39675349 · Full text
INTRODUCTION: The accurate distinction between benign and malignant biliary strictures (BSs) poses a significant challenge. Despite the use of bile duct biopsies and brush cytology via endoscopic retrograde cholangiopanc...
INTRODUCTION: The accurate distinction between benign and malignant biliary strictures (BSs) poses a significant challenge. Despite the use of bile duct biopsies and brush cytology via endoscopic retrograde cholangiopancreaticography (ERCP), the results remain suboptimal. Single-operator cholangioscopy can enhance the diagnostic yield in BS, but its limited availability and high costs are substantial barriers. Convolutional neural network-based systems may improve the diagnostic process and enhance reproducibility. Therefore, we assessed the feasibility of using deep learning to differentiate BS using fluoroscopy images during ERCP. METHODS: We conducted a retrospective review of adult patients (n = 251) from three university centers in Germany (Leipzig, Dresden, Halle) who underwent ERCP. We developed and evaluated a deep learning-based model using fluoroscopy images. The performance of the classifier was evaluated by measuring the area under the receiver operating characteristic curve (AUROC), and we utilized saliency map analyses to understand the decision-making process of the model. RESULTS: In cross-validation experiments, malignant BSs were detected with a mean AUROC of 0.89 ± 0.03. The test set of the Leipzig cohort demonstrated an AUROC of 0.90. In two independent external validation cohorts (Dresden, Halle), the deep learning-based classifier achieved an AUROC of 0.72 and 0.76, respectively. The artificial intelligence model's predictions identified plausible characteristics within the fluoroscopy images. CONCLUSION: By using a deep learning model, we were able to discriminate malignant BS from benign biliary conditions. The application of artificial intelligence enhances the diagnostic yield of malignant BS and should be validated in a prospective design.
Estimation of Invasion Depth of Early Colorectal Cancer Using Endoscopic Ultrasonography and Magnifying Chromoendoscopy: A Meta-Analysis.
Chen R, Huang Y, Liu F
Digestion · 2025 · PMID 39602913 · Publisher ↗
INTRODUCTION: Magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (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 co...
INTRODUCTION: Magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (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 <1,000 μm) 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 12,586 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.
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 … +5 more , Inooka K, Oka K, Takahashi M, Mano N, Fukudo S
Digestion · 2025 · PMID 39586243 · Full text
INTRODUCTION: 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...
INTRODUCTION: 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 aim was to investigate whether camostat mesilate (CM), a serine protease inhibitor, modifies fecal bacterial function related to FKBP-type PPIases in patients with IBS. METHODS: Randomly assigned 16 patients with IBS received 200 mg po tid of CM and 16 patients received placebo for 14 days. Self-reported adequate relief (AR) as a primary endpoint, IBS Symptom Severity Scale (IBS-SSS), and colonic motor and pain thresholds to colorectal distention were assessed before and after treatment. The fecal bacterial content was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: CM significantly increased the relative abundance of Streptococcus and the functional abundances of serine protease and FKBP-type PPIase FkpA, FklB and SlyD more than placebo after treatment. CM treatment was not superior to placebo in proportion of AR although colonic motor response partially changed. CONCLUSION: CM modulated the fecal microbiome composition and functional potentials that are related to FKBP-type PPIase activity in IBS patients. These findings suggest that protease inhibitors may modify gut microbial function along with abnormal immunological and/or stress responses that underlie pathophysiology of IBS.
Surveillance after Endoscopic Resection for Colorectal Tumors: A Comprehensive Review.
Hotta K, Matsuda T, Sano Y … +2 more , Fujii T, Saito Y
Digestion · 2025 · PMID 39571558 · Full text
BACKGROUND: 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...
BACKGROUND: 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 USA (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 CRC deaths during surveillance, bowel preservation, and emphasis on patient quality of life" as the guideline principles in Japan. SUMMARY: Randomized controlled trials to evaluate the appropriate surveillance intervals after endoscopic resection of colorectal tumors, the NPS, the Nottingham Study, and the Japan Polyp Study (JPS), are summarized. The ESGE, USMSTF, and Japanese guidelines compared low-risk adenoma, high-risk adenoma, advanced neoplasia, piecemeal resection, and serrated lesions by category. KEY MESSAGES: Surveillance guidelines based on risk stratification were developed in Japan. Guidelines are meaningful only when they are effectively utilized in clinical practice. They must also be revised based on new evidence. It is hoped that new knowledge will be accumulated, especially in Japan, on topics that are currently lacking. BACKGROUND: 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 USA (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 CRC deaths during surveillance, bowel preservation, and emphasis on patient quality of life" as the guideline principles in Japan. SUMMARY: Randomized controlled trials to evaluate the appropriate surveillance intervals after endoscopic resection of colorectal tumors, the NPS, the Nottingham Study, and the Japan Polyp Study (JPS), are summarized. The ESGE, USMSTF, and Japanese guidelines compared low-risk adenoma, high-risk adenoma, advanced neoplasia, piecemeal resection, and serrated lesions by category. KEY MESSAGES: Surveillance guidelines based on risk stratification were developed in Japan. Guidelines are meaningful only when they are effectively utilized in clinical practice. They must also be revised based on new evidence. It is hoped that new knowledge will be accumulated, especially in Japan, on topics that are currently lacking.
DYRK2 regulates epithelial-mesenchymal transition restriction in pancreatic cancer liver metastasis by inhibiting Twist.
Pan H, Liu Y, Bao K … +3 more , Wang Y, Zhang Y, Zhou L
Digestion · 2024 Nov · PMID 39561721 · Publisher ↗
OBJECTIVES: To explore the underlying variables and molecular pathways leading to pancreatic cancer liver metastasis. METHODS: Hs766T and Hs766T-L3 cells were used to create in vitro and in vivo pancreatic cancer liver m...
OBJECTIVES: To explore the underlying variables and molecular pathways leading to pancreatic cancer liver metastasis. METHODS: Hs766T and Hs766T-L3 cells were used to create in vitro and in vivo pancreatic cancer liver metastasis models. DYRK2 involvement in pancreatic cancer metastasis was investigated using cell adhesion assays, wound healing assays, and migration and invasion assays. To examine the link between DYRK2 expression and epithelial-mesenchymal transition, Western blot, quantitative real-time PCR, immunofluorescence assays, and immunoprecipitation (IP) were utilized. We found that mice with DYRK2 overexpression had a lower incidence of liver metastasis compared to controls. RESULTS: DYRK2 expression decreased pancreatic cancer tumorigenic activities, including proliferation, migration, and invasion. By analyzing the expression levels of epithelial-mesenchymal transition markers and IP results after overexpressing DYRK2, we found that DYRK2 decreased Twist levels by increasing Twist ubiquitination, thereby inhibiting epithelial-mesenchymal transition. CONCLUSIONS: Our findings provide theoretical and experimental support for the ongoing development of DYRK2-based targeted therapies for pancreatic cancer liver metastases.
Endoscopic Resection for Colorectal Tumors.
Hirai Y, Toyoshima N, Saito Y
Digestion · 2025 · PMID 39496235 · Publisher ↗
BACKGROUND: Endoscopic resection techniques for colorectal tumors are constantly evolving with improvements. SUMMARY: Over the past decade, there has been a paradigm shift toward cold polypectomy for the removal of small...
BACKGROUND: Endoscopic resection techniques for colorectal tumors are constantly evolving with improvements. SUMMARY: Over the past decade, there has been a paradigm shift toward cold polypectomy for the removal of small lesions (<10 mm), known as the "cold revolution". In recent years, underwater endoscopic mucosal resection (EMR) has emerged as an alternative to conventional EMR and has been gaining popularity for resection of intermediate and large-sized lesions (≥10 mm). Although colorectal endoscopic submucosal dissection (ESD) requires a high level of advanced skills, improvements in dissection techniques and devices have facilitated the procedure. In Japan, the safety and efficacy of ESD for resecting large lesions (≥20 mm) have been demonstrated in a large-scale, multicenter, prospective cohort study (CREATE-J). ESD is also being increasingly adopted in Western countries. As endoscopic resection continues to advance and include large and more complex defects, a variety of closure techniques and new devices are being developed. Meanwhile, the number of endoscopic resections for T1-colorectal cancer (T1-CRC), including those intended for total excisional biopsy, has been increasing owing to the aging population and improvements in endoscopic technique. KEY MESSAGES: This review provides a broad summary of endoscopic resection for colorectal tumors including advancements in closure techniques and devices for mucosal defects, as well as the potential role of endoscopic resection for patients with T1-CRC.
Implementation of Machine Learning Algorithms to Screen for Advanced Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: An In-Depth Explanatory Analysis.
Dabbah S, Mishani I, Davidov Y … +1 more , Ben Ari Z
Digestion · 2025 · PMID 39462487 · Full text
INTRODUCTION: This study aimed to train machine learning algorithms (MLAs) to detect advanced fibrosis (AF) in metabolic dysfunction-associated steatotic liver disease (MASLD) patients at the level of primary care settin...
INTRODUCTION: This study aimed to train machine learning algorithms (MLAs) to detect advanced fibrosis (AF) in metabolic dysfunction-associated steatotic liver disease (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 non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) on 540 MASLD patients from the primary care setting as validation. Feature importance, partial dependence, and shapely additive explanations (SHAPs) 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% versus 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 gamma glutamyl transpeptidase (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, low-density lipoprotein cholesterol, and alkaline phosphatase (p < 0.001). One-quarter of the false positives (FPs) 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.
Screening Colonoscopy to Reduce the Incidence and Mortality of Colorectal Cancer.
Tada N, Tamai N, Sumiyama K
Digestion · 2025 · PMID 39437753 · Publisher ↗
BACKGROUND: 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. SUMMARY: In addition to...
BACKGROUND: 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. SUMMARY: In addition to fecal immunochemical tests and computed tomography colonography, screening colonoscopy is expected to significantly contribute to the reduction of CRC. However, the timing of colonoscopy for CRC screening is not well-defined because of the lack of sufficient data. Additionally, the effectiveness of colonoscopy is affected by various factors known as quality indicators (QIs), such as the performance of the endoscopist; therefore, there are concerns regarding quality assurance. The adenoma detection rate (ADR) is a well-known QI of colonoscopy. Substantial evidence has suggested that improving the ADR could reduce the incidence and mortality of postcolonoscopy CRC. KEY MESSAGES: Recent technological advancements have led to the development of image-enhanced endoscopy and the incorporation of artificial intelligence, and their ability to improve the ADR has been assessed. This review focused on screening colonoscopies and QIs and their ability to improve the ADR and incidence and mortality of CRC.
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 … +29 more , 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, NHO Network Gastrointestinal Study Group
Digestion · 2025 · PMID 39406199 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (<30 days) and late (<1 year) rebleeding, length of hospital stay, and transfusion requirements. RESULTS: In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], -7.9 to 12.3; p = 0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, -9.4 to 10.4; p = 1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay, and transfusion requirements. CONCLUSION: The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN registry number, UMIN000026865).
The Link between Metabolic Syndrome and the Brain.
Zouridis S, Nasir AB, Aspichueta P … +1 more , Syn WK
Digestion · 2025 · PMID 39369701 · Full text
BACKGROUND: 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 a...
BACKGROUND: 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. SUMMARY: Studies have shown an association with minimal cognitive impairment, progression to vascular dementia, and even Alzheimer's disease. MetS components have been individually explored, and glucose intolerance has the strongest association with impairment in several cognitive domains. Several hypotheses have been proposed regarding the pathophysiology underlying the MetS-cognitive dysfunction association, and even though insulin resistance plays a major role, more studies are needed to elucidate this topic. Moreover, several other factors contributing to this association have been identified. Liver disease and more specifically metabolic dysfunction-associated steatotic liver disease can on its own contribute to cognitive decline through systemic inflammation and higher ammonia levels. Gut dysbiosis that has also been identified in MetS can also lead to cognitive impairment through several mechanisms that result in neurotoxicity. Finally, there are several other factors that may modify the MetS-cognitive dysfunction relationship, such as lifestyle, diet, education status, and age. More recently, circadian syndrome was explored and was found to be even more strongly associated with cognitive impairment. KEY MESSAGE: MetS is associated with cognitive decline. Certain cardiometabolic risk factors have a stronger association with cognitive impairment, and there are several factors that may modify this relationship. The aim of this review was to assess and summarize the existing body of evidence on the association between MetS and cognitive impairment and identify areas that necessitate further investigation.
NEIL3 Upregulated by TFAP2A Promotes M2 Polarization of Macrophages in Liver Cancer via the Mediation of Glutamine Metabolism.
Zhang F, Wang B, Zhang W … +3 more , Xu Y, Zhang C, Xue X
Digestion · 2025 · PMID 39342941 · Publisher ↗
INTRODUCTION: 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 macr...
INTRODUCTION: 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. METHODS: Bioinformatics analysis analyzed NEIL3 expression and its enriched pathways in liver cancer tissue, as well as its correlation with pathway genes. The upstream transcription factor of NEIL3, TFAP2A, was predicted and its expression in liver cancer tissue was analyzed. The binding relationship between the two was analyzed by dual-luciferase reporter and chromatin immunoprecipitation experiments. qRT-PCR assessed NEIL3 and TFAP2A levels in liver cancer cells. Cell viability was detected by CCK-8, while CD206 and CD86 expression was detected by immunofluorescence. IL-10 and CCR2 expressions were assessed using qRT-PCR, and M2 Mø quantity was detected using flow cytometry. Reagent kits tested glutamine (Gln) consumption, α-ketoglutarate, and glutamate content, as well as NADPH/NADP+ and GSH/GSSG ratios. Expression of Gln transport proteins was detected using Western blot. An animal model was established to investigate the influence of NEIL3 expression on liver cancer growth. RESULTS: NEIL3 was highly expressed in liver cancer and promoted Mø M2 polarization through Gln metabolism. TFAP2A was identified as the upstream transcription factor of NEIL3 and was highly expressed in liver cancer. Rescue experiments presented that overexpression of NEIL3 reversed the suppressive effect of TFAP2A knockdown on Mø M2 polarization in liver cancer. In vivo experiments demonstrated that the knockdown of NEIL3 could significantly repress the growth of xenograft tumors. CONCLUSION: This study suggested that the TFAP2A/NEIL3 axis promoted Mø M2 polarization through Gln metabolism, providing a theoretical basis for immune therapy targeting the liver cancer TME.
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 … +7 more , Matsuoka K, Keating M, Yuasa H, Oe M, Arai S, Mazur R, Hibi T
Digestion · 2025 · PMID 39317165 · Full text
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: Patients from Japan who completed the 12-week ELEVATE UC 12 induction trial could enroll in the 40-week ELEVATE UC 40 JAPAN maintenance trial for a combined 52-week treatment period. Patients in this Japan cohort continued their baseline assigned treatment (etrasimod 2 mg QD or placebo) from ELEVATE UC 12. Efficacy was assessed at week 12 and week 52. Treatment-emergent adverse events (TEAEs) pooled from both trials were assessed up to 52 weeks of exposure. RESULTS: The Japan cohort comprised 32 and 16 patients who received etrasimod and placebo, respectively. A numerically greater proportion of patients who received etrasimod versus placebo achieved clinical remission at week 12 (etrasimod: 14.3%; placebo: 7.1%) and week 52 (etrasimod: 25.0%; placebo: 7.1%); a similar trend was observed for all key secondary efficacy endpoints. TEAEs occurred in 84.4% (27/32) and 62.5% (10/16) of patients who received etrasimod and placebo, respectively. No new safety signals were detected. CONCLUSION: In these induction and maintenance trials evaluating etrasimod in patients from Japan with UC, numerically higher proportions of patients who received etrasimod versus placebo achieved efficacy endpoints. Efficacy and safety findings were consistent with those from the global ELEVATE UC trial populations.
Artificial Intelligence for Contrast-Enhanced Ultrasound of the Liver: A Systematic Review.
Brooks JA, Kallenbach M, Radu IP … +5 more , Berzigotti A, Dietrich CF, Kather JN, Luedde T, Seraphin TP
Digestion · 2025 · PMID 39312896 · Full text
INTRODUCTION: 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 colorecta...
INTRODUCTION: 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. METHODS: In this systematic review, we analyzed and compared original research studies applying AI methods to CEUS examinations of the liver published between January 2010 and February 2024. We performed a structured literature search on PubMed, Web of Science, and IEEE. Two independent reviewers screened the articles and subsequently extracted relevant methodological features, e.g., cohort size, validation process, machine learning algorithm used, and indicative performance measures from the included articles. RESULTS: We included 41 studies with most applying AI methods for classification tasks related to focal liver lesions. These included distinguishing benign versus malignant or classifying the entity itself, while a few studies tried to classify tumor grading, microvascular invasion status, or response to transcatheter arterial chemoembolization directly from CEUS. Some articles tried to segment or detect focal liver lesions, while others aimed to predict survival and recurrence after ablation. The majority (25/41) of studies used hand-picked and/or annotated images as data input to their models. We observed mostly good to high reported model performances with accuracies ranging between 58.6% and 98.9%, while noticing a general lack of external validation. CONCLUSION: Even though multiple proof-of-concept studies for the application of AI methods to CEUS examinations of the liver exist and report high performance, more prospective, externally validated, and multicenter research is needed to bring such algorithms from desk to bedside.
Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review.
Chu P, Mioc J, O'Donovan P … +1 more , Henry O
Digestion · 2025 · PMID 39299226 · Full text
INTRODUCTION: 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 the...
INTRODUCTION: 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. METHODS: A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria. RESULTS: We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. CONCLUSIONS: This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes. INTRODUCTION: 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. METHODS: A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria. RESULTS: We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. CONCLUSIONS: This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.
C-Kit Immunohistochemical Expression as a Complementary Method to Assess Mast Cell Density in Helicobacter pylori-Mediated Gastritis.
Ismael AT, Abdulhameed RA, Hamdi BA … +2 more , Tawfeeq RD, Ommar A
Digestion · 2025 · PMID 39278202 · Publisher ↗
INTRODUCTION: 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. Ad...
INTRODUCTION: 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). METHODS: This retrospective, cross-sectional study was conducted in Iraqi Kurdistan with a sample size of 380 patients. Patient data included gastritis type, neutrophil infiltration severity, mononuclear cell infiltration within the lamina propria, intestinal metaplasia, and glandular atrophy, which were categorized and given a score. The CD117 level was identified using an anti-human rabbit polyclonal antibody. RESULTS: A statistically significant association was revealed between Helicobacter pylori-mediated gastritis and non-specific gastritis with age, activity, H. pylori and MCD, dysplasia, and malignancy. Meanwhile, no association was found with gender, inflammatory infiltrate, intestinal metaplasia, and glandular atrophy. C-Kit exhibited a marked increase in MCD in patients with H. pylori-mediated gastritis, intestinal metaplasia, atrophy, and gastric carcinoma. However, a significant decrease in MCD was observed on repeating endoscopy evaluations for patients after treatment. CONCLUSION: Regions that exhibit severe inflammation, metaplasia, atrophy, and carcinoma demonstrated an increase in MCD with H. pylori-mediated gastritis. A detailed investigation in clinical practice to screen early diagnosis and treatment needs to be performed in high H. pylori prevalence.
Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.
Ihara E, Manabe N, Ohkubo H … +34 more , 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, Higuchi K
Digestion · 2024 · PMID 39197422 · Full text
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 test...
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.
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 … +1 more , Cao Q
Digestion · 2025 · PMID 39182484 · Full text
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correction" and "Robust rank aggregation" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by "AddModuleScore" and "AUCell." RESULTS: Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001). CONCLUSION: This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment. INTRODUCTION: 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. METHODS: Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correction" and "Robust rank aggregation" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by "AddModuleScore" and "AUCell." RESULTS: Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001). CONCLUSION: This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.
Erratum.
Digestion · 2024 · PMID 39173592 · Publisher ↗
Abstract loading — click title to view on PubMed.
Evidence-Based Clinical Guidelines for Chronic Constipation 2023.
Ihara E, Manabe N, Ohkubo H … +34 more , 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, Higuchi K
Digestion · 2025 · PMID 39159626 · Full text
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, diag...
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. 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.
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 … +16 more , 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, Sakuraba H
Digestion · 2024 · PMID 39102805 · Full text
INTRODUCTION: 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 unclea...
INTRODUCTION: 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. METHODS: Patients with esophageal achalasia and EGJOO who underwent POEM were allocated to the EMD group. Biopsies of the inner circular muscle were conducted during the POEM procedure. The control group comprised individuals diagnosed with esophageal squamous cell carcinoma who underwent surgical resection. Expression of pattern recognition receptors, including Toll-like receptor (TLR) 7, was examined by polymerase chain reaction. Immunohistochemical staining was performed to determine TLR7 expression sites in the esophageal muscle layer, and the relationship between TLR7 mRNA expression and clinical score was investigated. RESULTS: Our analysis revealed a notable upregulation of TLR7 mRNA levels within the muscle layer of esophageal achalasia and EGJOO, in contrast to those of control specimens. In contrast, the correlation between TLR7 and clinical score was not significant. Immunohistochemical staining revealed increased numbers of TLR7-expressing macrophages between the muscle layers. CONCLUSIONS: TLR7-expressing macrophages are involved in the innate immune response underlying esophageal achalasia and EGJOO. This result will lead to the elucidation of new pathogenetic mechanisms and the development of novel therapeutic targets.
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