Pediatric duodenal stenosis caused by posttraumatic mesenteric hematoma managed with a double elementary diet tube.

A 6-year-old male child was admitted to the hospital because of abdominal trauma and acute stomach pain. Computed tomography scan revealed a jejunal mesenteric hematoma and an enhanced intestinal wall compressed by the hematoma. The patient presented with vomiting 10 days after the injury. He underwent upper endoscopy under tracheal intubation and general anesthesia 12 days after the injury. A double elementary diet tube was inserted endoscopically with the tip placed in the jejunum beyond the stenosis and the decompressed portion of the stomach. Stenosis was improving, and the patient was discharged on the 27th day after the injury. In conclusion, a double elementary diet tube can be effective for treating posttraumatic duodenal stenosis in pediatric patients.

A Novel Organoid-Based Strategy Using Hybrid Colon Interposition for Short Bowel Syndrome: A Mini Review of In Vivo Models and Possible Human Candidates.

This comprehensive review focuses on advances in surgical techniques and in vivo animal models for treating short bowel syndrome (SBS) with intestinal organoids. Notably, this review discusses a novel method involving the replacement of the epithelium of large intestinal tissue with small intestinal organoids, which improves function and prognosis when grafted back into the small intestine. This study not only underscores the importance of integrating organoid technology and surgical techniques to improve the outcomes of patients with SBS but also acknowledges the challenges that lie ahead, including achieving functional organoids with peristaltic movement and vascularization.

Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.

Hedgehog (Hh) signaling, an evolutionarily conserved pathway, plays an essential role in development and tumorigenesis, making it a promising drug target. Multiple negative regulators are known to govern Hh signaling; however, how activated Smoothened (SMO) participates in the activation of downstream GLI2 and GLI3 remains unclear. Herein, we identified the ciliary kinase DYRK2 as a positive regulator of the GLI2 and GLI3 transcription factors for Hh signaling. Transcriptome and interactome analyses demonstrated that DYRK2 phosphorylates GLI2 and GLI3 on evolutionarily conserved serine residues at the ciliary base, in response to activation of the Hh pathway. This phosphorylation induces the dissociation of GLI2/GLI3 from suppressor, SUFU, and their translocation into the nucleus. Loss of Dyrk2 in mice causes skeletal malformation, but neural tube development remains normal. Notably, DYRK2-mediated phosphorylation orchestrates limb development by controlling cell proliferation. Taken together, the ciliary kinase DYRK2 governs the activation of Hh signaling through the regulation of two processes: phosphorylation of GLI2 and GLI3 downstream of SMO and cilia formation. Thus, our findings of a unique regulatory mechanism of Hh signaling expand understanding of the control of Hh-associated diseases.

Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy.

Background/Aims: Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features. Methods: This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component. Results: Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%). Conclusions: This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

Pancreatic stent migration into the main pancreatic duct during endoscopic papillary balloon dilation.

We report the first case of pancreatic stent (PS) migration placed early into the main pancreatic duct (MPD) during endoscopic retrograde cholangiopancreatography (ERCP) due to subsequent endoscopic papillary balloon dilation. A 74-year-old woman who complained of fever and abdominal pain was diagnosed with acute calculous cholangitis. On ERCP, a needle-knife precut papillotomy was performed from the orifice because of difficult cannulation. Because of unintentional guidewire insertion into the MPD from the orifice, a PS with bilateral flaps was promptly placed to prevent post-ERCP pancreatitis. After successful biliary cannulation from the orifice alongside the PS, endoscopic papillary balloon dialtion was performed, leading to PS migration into the MPD during the dilation. Two days after the first ERCP, the migrated PS was successfully removed on the second ERCP. The strategy of early PS placement in the ERCP session appears theoretically promising for preventing post-ERCP pancreatitis. However, early PS placement during the ERCP session should be noted to pose the risk of migration into the MPD, especially when pushing the device into the bile duct.

Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

BACKGROUND: Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. METHODS: An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MES of 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. RESULTS: The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). CONCLUSIONS: Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.

Dose escalation of 5-aminosalicylic acid for ulcerative colitis reduced relapse rate in patients in clinical remission with a Mayo endoscopic subscore of 1. The therapeutic efficacy was more evident in those whom immunomodulators were used.

Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis.

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Migration of a Common Bile Duct Stone into the Main Pancreatic Duct due to Catheter Manipulation during Endoscopic Retrograde Cholangiopancreatography.

Introduction: We report the first case of a choledocholithiasis migrating into the main pancreatic duct (MPD) due to catheter manipulation during endoscopic retrograde cholangiopancreatography (ERCP). Case Presentation: A 57-year-old woman complaining of vomiting was diagnosed with acute cholangitis and pancreatitis due to choledocholithiasis. During ERCP, the stone migrated from the papilla into the MPD due to the pushing motion of the catheter. However, the ERCP session was completed after biliary sphincterotomy without intervention in the MPD because the migration was not noticed. The migrated stone became apparent on computed tomography the following day. The second ERCP revealed the stone measuring 5 mm in the MPD. After pancreatic sphincterotomy, a pancreatic stent was placed, which improved the obstructive pancreatitis. Conclusion: Endoscopists performing ERCP should be aware of this rare but serious complication.

Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split-dose 2-L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E-PLUS trial.

BACKGROUND: Sodium picosulfate (SP)/magnesium citrate (MC) and polyethylene glycol (PEG) plus ascorbic acid are recommended by Western guidelines as laxative solutions for bowel preparation. Clinically, SP/MC has a slower post-dose defaecation response than PEG and is perceived as less cleansing; therefore, it is not currently used for major bowel cancer screening preparation. The standard formulation for bowel preparation is PEG; however, a large dose is required, and it has a distinctive flavour that is considered unpleasant. SP/MC requires a small dose and ensures fluid intake because it is administered in another beverage. Therefore, clinical trials have shown that SP/MC is superior to PEG in terms of acceptability. We aim to compare the novel bowel cleansing method (test group) comprising SP/MC with elobixibat hydrate and the standard bowel cleansing method comprising PEG plus ascorbic acid (standard group) for patients preparing for outpatient colonoscopy. METHODS: This phase III, multicentre, single-blind, noninferiority, randomised, controlled, trial has not yet been completed. Patients aged 40-69 years will be included as participants. Patients with a history of abdominal or pelvic surgery, constipation, inflammatory bowel disease, or severe organ dysfunction will be excluded. The target number of research participants is 540 (standard group, 270 cases; test group, 270 cases). The primary endpoint is the degree of bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥ 6). The secondary endpoints are patient acceptability, adverse events, polyp/adenoma detection rate, number of polyps/adenomas detected, degree of bowel cleansing according to the BBPS (BBPS score ≥ 8), degree of bowel cleansing according to the Aronchik scale, and bowel cleansing time. DISCUSSION: This trial aims to develop a "patient-first" colon cleansing regimen without the risk of inadequate bowel preparation by using both elobixibat hydrate and SP/MC. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; no. s041210067; 9 September 2021; https://jrct.niph.go.jp/ ), protocol version 1.5 (May 1, 2023).

Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study.

BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

Characteristics of flat-type ulcerative colitis-associated neoplasia on chromoendoscopic imaging with indigo carmine dye spraying.

OBJECTIVES: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. METHODS: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. RESULTS: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. CONCLUSION: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

Clinical challenges of short bowel syndrome and the path forward for organoid-based regenerative medicine.

Short bowel syndrome (SBS) is a rare condition, the main symptom of which is malabsorption following extensive resection of the small intestine. Treatment for SBS is mainly supportive, consisting of supplementation, prevention and treatment of complications, and promotion of intestinal adaptation. While development of parenteral nutrition and drugs promoting intestinal adaptation has improved clinical outcomes, the prognosis of patients with SBS remains poor. Intestinal transplantation is the only curative therapy but its outcome is unsatisfactory. In the absence of definitive therapy, novel treatment is urgently needed. With the advent of intestinal organoids, research on the intestine has developed remarkably in recent years. Concepts such as the "tissue-engineered small intestine" and "small intestinalized colon," which create a functional small intestine by combining organoids with other technologies, are potentially novel regenerative therapeutic approaches for SBS. Although they are still under development and there are substantial issues to be resolved, the problems that have prevented establishment of the complex function and structure of the small intestine are gradually being overcome. This review discusses the current treatments for SBS, the fundamentals of the intestine and organoids, the current status of these new technologies, and future perspectives.

Correction: Reopenable clip-over-the-line method for closing large mucosal defects following colorectal endoscopic submucosal dissection: A feasibility study.

[This corrects the article DOI: 10.1055/a-2095-0033.].

Reopenable clip-over-the-line method for closing large mucosal defects following colorectal endoscopic submucosal dissection: A feasibility study.

Background and study aims Complete closure of large defects after colorectal endoscopic submucosal dissection (ESD) can be problematic, especially in challenging areas or lesions larger than half the lumen circumference. We report a reopenable clip-over-the-line method for such defects and aim to investigate its feasibility through a case series. Patients and methods We retrospectively evaluated data from 30 consecutive patients who underwent ESD with defect closure using the reopenable clip-over-the-line method between October 2020 and September 2022. This method requires the first clip-with-line grasp of the oral side's defect edge and muscle layer. The next reopenable clip (with a line fed through a hole in the reopenable clip tooth) is placed on the opposing mucosal defect edge and muscle layer. This process is repeated until complete closure. The primary study outcome was the rate of complete mucosal defect closure. We also reported post-procedure bleeding or perforation. Results The median dimensions of the resected specimens were 45 mm (range, 35-70) by 39 mm (range, 29-60). Complete closure was achieved for all defects, including nine rectal defects, of which three bordered the anal verge. Of the 30 defects included in this study, nine were larger than half the lumen circumference. The median closure time was 25 minutes (range, 14-52), and the median clip number was 17 (range, 9-42). No post-procedure bleeding or perforation occurred. Conclusions The reopenable clip-over-the-line method is a feasible technique for the complete closure of large colorectal defects after endoscopic submucosal dissection, regardless of location.