Extended total colonic aganglionosis and total intestinal aganglionosis: Challenging enemies.

AIM: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. METHODS: A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). RESULTS: Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. CONCLUSION: Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

Malignant myopericytoma originating from the colon: A case report.

BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.

In vitro human colonic fermentation of coffee arabinogalactan and melanoidin-rich fractions.

Coffee beverage is a source of dietary fiber composed by arabinogalactans, which can also be associated to proteins and phenolic compounds, originating melanoidins. Human colonic in vitro fermentations of coffee fractions, one rich in melanoidins (Mel) and the other in its parental polysaccharide arabinogalactans (AG), were performed in order to evaluate the metabolites produced by microbiota, namely short-chain fatty acids (SCFA), phenolic compounds, and bile acids. After 48 h of fermentation, a higher fermentability of the carbohydrate fraction of AG (62 %) than that of Mel (27 %) was observed, resulting in a SCFA content of 63 mM and 22 mM, respectively. Supplementation with AG and Mel fractions decreased the acetate:propionate ratio from 4.7 (in the absence of coffee fractions) to 2.5 and 3.5, respectively, suggesting a potential inhibition of HMG-CoA reductase, a rate-limiting enzyme for cholesterol synthesis. The fermentation of coffee fractions yielded dihydroferulic and dihydrocaffeic acids, known to have antioxidant properties. In the presence of Mel, it was observed a decrease (from 0.25 to 0.16 mg/mL) in the production of secondary bile acids, whose high content is associated to the development of several diseases, such as colorectal cancer, neurodegenerative and cardiovascular.

Anti-inflammation mechanisms of a homogeneous polysaccharide from Phyllanthus emblica L. on DSS induced colitis mice via the gut microbiota and metabolites alteration.

Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.

Usefulness of the one-step technique in functional end-to-end anastomosis for colonic surgery: results of a prospective multicentre cohort study from the Japanese KYCC group.

BACKGROUND: Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. METHODS: This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade 2 or higher were assessed. RESULTS: Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade 3, two patients; grade 2) while the TS group had one case (1.0%) of grade 2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). CONCLUSIONS: The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. TRIAL REGISTRATION NUMBER: UMIN000039902 (registration date 23 March 2020).

Diaphragmatic eventration associated with megacolon: A case report.

INTRODUCTION: Diaphragmatic eventration (DE) associated with gastrointestinal anomalies is rarely reported, and its treatment is not well defined. CASE PRESENTATION: We present a 24-years-old male admitted for cough, dyspnea, and chest pain, all of gradual onset. Chest computerized tomography (CT) and chest x-ray diagnosed diaphragmatic eventration and colonic distension. He underwent surgery via a posterolateral thoracotomy. We found colonic distension which pushed the left hemidiaphragm under intense pressure further into the chest, making immediate diaphragmatic plication via the chest difficult. We managed this by colonic needle decompression followed by resection and plication of the diaphragm. The patient had a satisfactory postoperative recovery with a good respiratory profile and no constipation. At a follow up visit, barium enema showed megacolon with no apparent etiology. He is to have a long-term outpatient follow up. DISCUSSION: Diaphragmatic eventration coexisting with megacolon is rare. Data available suggests supplementary abdominal workup is necessary to better plan the surgery. Surgical correction via an abdominal route tends to be more appropriate in these scenarios. CONCLUSION: In cases of gastrointestinal anomaly associated with diaphragmatic eventration, more careful abdominal consideration is needed to better plan the surgery.

Cranial-first approach for laparoscopic extended right hemicolectomy.

Complete mesocolic excision and central vascular ligation with D3 lymphadenectomy are important surgical principles for improving oncological outcomes in colon cancer. The cranial-first approach is a colonic mobilization-first approach to radical right hemicolectomy, which has several advantages, including early feasibility assessment, safe dissection from surrounding organs, preestablished inferior margin of lymph node dissection, and revelation of the tangible anatomy of the tributaries of the gastrocolic trunk. This video demonstrates the cranial-first approach to radical right hemicolectomy in a 66-year-old man with locally advanced cecal cancer.

Preoperative localization of potentially invisible colonic lesions on the laparoscopic operation field: using autologous blood tattooing.

PURPOSE: Preoperative colonoscopic (POC) localization is recommended for patients scheduled for elective laparoscopic colectomy for early colon cancer. Among the various localization method, POC tattooing localization has been widely used. Several dyes have been used for tattooing, but dye has disadvantages, including foreign body reactions. For this reason, we have used autologous blood tattooing for POC localization. This study aimed to evaluate the safety and efficacy of the autologous blood tattooing method. METHODS: This study included patients who required POC localization of the colonic neoplasm among the patients who were scheduled for elective colon resection. The indication for localization was early colon cancer (clinically T1 or T2) or colonic neoplasms that could not be resected endoscopically. POC autologous blood tattooing was performed after saline injection, and 2 hemoclips were applied. RESULTS: A total of 45 patients who underwent autologous blood tattooing and laparoscopic colectomy were included in this study. All POC localization sites were visible in the laparoscopic view. POC localization sites showed almost perfect agreement with intraoperative surgical findings. There were no complications like bowel perforation, peritonitis, hemoperitoneum, and mesenteric hematoma. CONCLUSION: Autologous blood is a safe and effective agent for localizing materials that can replace previous dyes. However, a large prospective case-control study is required for the routine application of this procedure in early colon cancer or colonic neoplasms.

Cold versus hot snare endoscopic mucosal resection for large (≥15 mm) flat non-pedunculated colorectal polyps: a randomised controlled trial.

BACKGROUND AND AIMS: Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR. METHODS: Flat, 15-50 mm adenomatous LNPCPs were prospectively enrolled and randomly assigned to C-EMR or H-EMR with margin thermal ablation at a single tertiary centre. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at 6 months surveillance colonoscopy. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success. RESULTS: 177 LNPCPs in 177 patients were randomised to C-EMR arm (n=87) or H-EMR (n=90). Treatment groups were equivalent for technical success 86/87 (98.9%) C-EMR versus H-EMR 90/90 (100%); p=0.31. Recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; relative risk (RR) 16.6, 95% CI 2.24 to 122; p<0.001).Delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB was significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); RR 6.77, 95% CI 0.85 to 53.9; p=0.034). CONCLUSION: Compared with H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique. TRIAL REGISTRATION NUMBER: NCT04138030.

[Gastric and colic digestive localizations of myeloma; 3 case studies and literature review]. / Localisations digestives gastriques et coliques de myélomes ; étude de 3 cas et revue de la littérature.

Multiple myeloma is a malignant plasma cell proliferation located in the bone marrow and bones. It can secondarily manifest with extraosseous involvement, but the gastro-intestinal tract locations are rare. We report 3 cases of gastric and colonic localizations of myeloma in two males and one female, aged 66, 71 and 77years. Multiple myeloma had been diagnosed 1 to 7years before. Digestive symptoms were epigastric pain, rectal bleeding or an obstructive syndrome. Endoscopy revealed ulcerated and budding tumors in the stomach, and nodular pseudo-polypoid tumor formations or an ulcerated erythematous area in the colon. Histopathological examination of the biopsies showed a diffuse tumor cell proliferation in the lamina propria composed of cells with a plasmacytoid or plasmablastic appearance, expressing plasma cell markers such as CD138 on immunohistochemistry. The 3 patients died in the weeks following the diagnosis. The prognosis of digestive localizations of multiple myeloma remains very poor despite new therapies. In the presence of any digestive symptoms in these patients with multiple myeloma, more systematic endoscopy may allow an earlier diagnosis and the implementation of more effective therapies.

Clinical outcomes of endoscopic detachable snare ligation for colonic diverticular hemorrhage: Multicenter cohort study.

OBJECTIVES: The hemostatic mechanism of endoscopic detachable snare ligation (EDSL) for colonic diverticular hemorrhage (CDH) is similar to that of endoscopic band ligation, which is effective and safe. However, because reports on EDSL are scarce, we conducted a two-center cohort study to evaluate its effectiveness. METHODS: This study analyzed 283 patients with CDH treated with EDSL at two Japanese hospitals between July 2015 and November 2021. Patient characteristics and clinical outcomes were retrospectively evaluated. A Kaplan-Meier analysis was performed to evaluate the cumulative probability of rebleeding after EDSL. A Cox proportional hazards regression analysis was performed to compare the effects of complete and incomplete ligation on rebleeding. RESULTS: The initial hemostasis success and early rebleeding rates were 97.9% and 11.0%, respectively. The time to hemostasis after identification of the bleeding site and total procedure time were 9 min and 44 min, respectively. Red blood cell transfusion was required for 32.9% of patients. The median hospital length of stay after EDSL was 5 days. The complete ligation rate of the early rebleeding group was significantly lower than that of the group without early rebleeding (P < 0.01). The 1-year cumulative rebleeding rate with EDSL was 28.2%. Complete ligation was associated with decreased cumulative rebleeding after EDSL (P < 0.01). One patient experienced colonic diverticulitis; however, colonic perforation was not observed. CONCLUSION: Complete ligation is associated with reduced short-term and long-term rebleeding. EDSL could be valuable for CDH because of its low rebleeding rate and the absence of serious adverse events.

Polysaccharide-polyphenol interactions: a comprehensive review from food processing to digestion and metabolism.

Most studies on the beneficial effects of polyphenols on human health have focused on polyphenols extracted using aqueous organic solvents, ignoring the fact that a portion of polyphenols form complexes with polysaccharides. Polysaccharides and polyphenols are interrelated, and their interactions affect the physicochemical property, quality, and nutritional value of foods. In this review, the distribution of bound polyphenols in major food sources is summarized. The effect of food processing on the interaction between polyphenols and cell wall polysaccharides (CWP) is discussed in detail. We also focus on the digestion, absorption, and metabolic behavior of polysaccharide-polyphenol complexes. Different food processing techniques affect the interaction between CWP and polyphenols by altering their structure, solubility, and strength of interactions. The interaction influences the free concentration and extractability of polyphenols in food and modulates their bioaccessibility in the gastrointestinal tract, leading to their major release in the colon. Metabolism of polyphenols by gut microbes significantly enhances the bioavailability of polyphenols. The metabolic pathway and product formation rate of polyphenols and the fermentation characteristics of polysaccharides are affected by the interaction. Furthermore, the interaction exhibits synergistic or antagonistic effects on the stability, solubility, antioxidant and functional activities of polyphenols. In summary, understanding the interactions between polysaccharides and polyphenols and their changes in food processing is of great significance for a comprehensive understanding of the health benefits of polyphenols and the optimization of food processing technology.

Gastrointestinal functions after laparoscopic right colectomy with intracorporeal anastomosis: a pilot randomized clinical trial on effects of abdominal drain, prolonged antibiotic prophylaxis, and D3 lymphadenectomy with complete mesocolic excision.

PURPOSE: Routine use of abdominal drain or prolonged antibiotic prophylaxis is no longer part of current clinical practice in colorectal surgery. Nevertheless, in patients undergoing laparoscopic right hemicolectomy with intracorporeal anastomosis (ICA), it may reduce perioperative abdominal contamination. Furthermore, in cancer patients, prolonged surgery with extensive dissection such as central vascular ligation and complete mesocolon excision with D3 lymphadenectomy (altogether radical right colectomy RRC) is called responsible for affecting postoperative ileus. The aim was to evaluate postoperative resumption of gastrointestinal functions in patients undergoing right hemicolectomy for cancer with ICA and standard D2 dissection or RRC, with or without abdominal drain and prolonged antibiotic prophylaxis. METHODS: Monocentric factorial parallel arm randomized pilot trial including all consecutive patients undergoing laparoscopic right hemicolectomy and ICA for cancer, in 20 months. Patients were randomized on a 1:1:1 ratio to receive abdominal drain, prolonged antibiotic prophylaxis or neither (I level), and 1:1 to receive RRC or D2 colectomy (II level). Patients were not blinded. The primary aim was the resumption of gastrointestinal functions (time to first gas and stool, time to tolerated fluids and food). Secondary aims were length of stay and complications' rate. CLINICALTRIALS: gov no. NCT04977882. RESULTS: Fifty-seven patients were screened; according to sample size, 36 were randomized, 12 for each arm for postoperative management, and 18 for each arm according to surgical techniques. A difference in time to solid diet favored the group without drain or antibiotic independently from standard or RRC. Furthermore, when patients were divided with respect to surgical technique and into matched cohorts, no differences were seen for primary and secondary outcomes. CONCLUSION: Abdominal drainage and prolonged antibiotic prophylaxis in patients undergoing right hemicolectomy for cancer with ICA seem to negatively affect the resumption of a solid diet after laparoscopic right hemicolectomy with ICA for cancer. RRC does not seem to influence gastrointestinal function recovery.

Ingested Foreign Bodies in the Sigmoid Colon Requiring Earlier Intervention in Patients With Prior Hysterectomy.

The use of dentures and dental plates is widespread in the adult population. Accidental ingestion of these foreign objects is not uncommon, with the majority of patients having an uneventful passage of the object through the gastrointestinal tract. Of those patients requiring intervention, endoscopy is the most common, followed by surgical removal. We discuss a case of a patient with prior pelvic surgery and diverticulosis causing severe angulation of the bowel, resulting in non-passage of the foreign object requiring surgical intervention.

Eosinophilic gastroenteritis in an elderly men associated with antibiotic use post maxillofacial space infection: a case report.

A 79-year-old man underwent operative drainage and 2-week cephalosporin treatment due to a maxillofacial space infection (bilateral submaxillaris, submentum, and left face). However, he experienced anorexia, nausea, vomiting, and emaciation in the following 2 months. It was initially considered that a malignancy might be present, thus a series of examinations were performed. Laboratory investigations showed increases in inflammatory markers and a significant eosinophilia, which seemed to be a hematological system disease. Combined with the gastrointestinal endoscopes and histology examination, the patient was diagnosed with eosinophilic gastroenteritis (EGE). After cessation of antibiotic treatment and administration of corticosteroid, our patient experienced a rapid progress in his clinical condition. Despite the low incidence, EGE should be considered in patients with unknown cause of gastrointestinal disorder, elevated eosinophilia, and so on.

Recent advances in measuring the effects of diet on gastrointestinal physiology: Probing the "leaky gut" and application of real-time ultrasound.

There is a large pool of ideas in both mainstream and non-mainstream medicine on how diet can be manipulated in order to treat or prevent illnesses. Despite this, our understanding of how specific changes in diet influence the structure and function of the gastrointestinal tract is limited. This review aims to describe two areas that might provide key information on the integrity and function of the gastrointestinal tract. First, demystifying the "leaky gut syndrome" requires rational application and interpretation of tests of intestinal barrier function. Multiple ways of measuring barrier function have been described, but the inherent difficulties in translation from animal studies to humans have created misinterpretations and misconceptions. The intrinsic nature of intestinal barrier function is dynamic. This is seldom considered in studies of intestinal barrier assessment. To adequately understand the effects of dietary interventions on intestinal barrier function, background barrier function in different regions of the gut and the dynamic responses to stressors (such as psychological stress) should be assessed as a minimum. Second, intestinal ultrasound, which is now established in the assessment and monitoring of inflammatory bowel disease, has hitherto been poorly evaluated in assessing real-time intestinal function and novel aspects of structure in patients with disorders of gut-brain interaction. In conclusion, a more complete functional and structural profile that these investigations enable should permit a greater understanding of the effects of dietary manipulation on the gastrointestinal tract and provide clinically relevant information that, amongst other advantages, might permit opportunities for personalized health care delivery.

Multiomics reveals the ameliorating effect and underlying mechanism of aqueous extracts of polygonatum sibiricum rhizome on obesity and liver fat accumulation in high-fat diet-fed mice.

BACKGROUND: Polygonatum sibiricum polysaccharides protect against obesity and NAFLD. However, the potential effects of PS rhizome aqueous extracts (PSRwe) on adiposity and hepatic lipid accumulation remains unexplored. PURPOSE: Elucidating the impact and underlying mechanism of PSRwe on HFD-induced obesity and liver fat depostition. STUDY DESIGN: 56 male mice, aged eight weeks, were divided into seven groups: Positive, four doses of PSRwe, Model, and Control. HFD was fed for eight weeks, followed by alternate-day gavage of orlistat and PSRwe for an additional eight-week period. Integrative analysis encompassing multiomics, physiological and histopathological, and biochemical indexes was employed. METHODS: Body weight (BW); liver, fat and Lee's indexes; TC, TG, LDL-C, HDL-C, AST, ALT, FFA, leptin, and adiponectin in the liver and blood; TNFα, IL-6, and LPS in the colon, plasma, and liver; H&E, PAS and oil red O staining on adipose and liver samples were examined. OGTT and ITT were conducted The gut microbiome, microbial metabolome, colonic and liver transcriptome, plasma and liver metabolites were investigated. RESULTS: PSRwe at the dosage of 7.5 mg/kg demonstrated significant and consistent reduction in BW and hepatic fat deposition than orlistat. PSRwe significantly decreased TC, TG, LDL-C, LEP, FFA levels in blood and liver. PSRwe significantly enhanced the relative abundance of probiotics including Akkermansia muciniphila, Bifidobacterium pseudolongum, Lactobacillus reuteri, and metabolic pathways including glycolysis and fatty acids ß-oxidation. The 70 up-regulated microbial metabolites in PSRwe-treated mice mainly involved in nucleotides and amino acids metabolism, while 40 decreased metabolites primarily associated with lipid metabolism. The up-regulated colonic differentially expressed genes (DEGs) participate in JAK-STAT/PI3K-Akt/FoxO signaling pathway, serotonergic/cholinergic/glutamatergic synapses, while the down-regulated DEGs predominantly focused on fat absorption and transport. The up-regulated liver DEGs mainly concentrated on fatty acid oxidation and metabolism. Liver metabolisms revealed 131 differential metabolites, among which carnitine and oxidized lipids significantly increased in PSRwe-treated mice. In plasma, the 58 up-regulated metabolites mainly participate in co-factors/vitamins metabolism while 154 down-regulated ones in fatty acids biosynthesis. Comprehensive multiomics association analysis revealed significant associations between gut microbiota and colonic/liver gene expression, and suggested exogenous and endogenous betaine may be active compound in alleviating HFD-induced symptoms. CONCLUSION: PSRwe effectively mitigate HFD-induced obesity and hepatic steatosis by increasing beneficial bacteria, reducing colonic fat digestion/absorption, increasing hepatic lipid metabolism, and elevating betaine levels.

Exploring the interactions of JAK inhibitor and S1P receptor modulator drugs with the human gut microbiome: Implications for colonic drug delivery and inflammatory bowel disease.

The gut microbiota is a complex ecosystem, home to hundreds of bacterial species and a vast repository of enzymes capable of metabolising a wide range of pharmaceuticals. Several drugs have been shown to affect negatively the composition and function of the gut microbial ecosystem. Janus Kinase inhibitors and Sphingosine-1-phosphate receptor modulators are drugs recently approved for inflammatory bowel disease through an immediate release formulation and would potentially benefit from targeted colonic targeted delivery to enhance the local drug concentration at the diseased site. However, their impact on the human gut microbiota and susceptibility to bacterial metabolism remain unexplored. With the use of calorimetric, optical density measurements, and metagenomics next-generation sequencing, we show that JAK inhibitors have a minor impact on the composition of the human gut microbiota, while ozanimod exerts a significant antimicrobial effect, leading to a prevalence of the Enterococcus genus and a markedly different metabolic landscape when compared to the untreated microbiota. Moreover, ozanimod is the only drug subject to enzymatic degradation by the human gut microbiota sourced from six healthy donors.. Overall, given the crucial role of the gut microbiome in health, screening assays to investigate the interaction of drugs with the microbiome should be encouraged for the pharmaceutical industry as a standard in the drug discovery and development process.

Surgical maneuvers for long-segment Hirschsprung pull-through in unique patients.

PURPOSE: Patients with Hirschsprung disease affecting the splenic flexure or more proximal segments present a surgical challenge. Mobilizing the transverse colon to the pelvis during a pull-through may obstruct the distal ileum, or the length may be insufficient to reach the lower pelvis. This retrospective study aimed to describe two surgical techniques that facilitate mobilization of the transverse colon and their outcome. METHODS: We included patients operated on between April 2017 and April 2024 and analyzed sex, comorbidities, type of pull- through, age at pull-through, history of previous surgeries, cause of the proximal transverse colon pull-through, technique used (Deloyers or Turnbull), complications , postoperative outcome and follow-up. The first technique used was the maneuver described by Turnbull. This operation creates a mesenteric defect and mobilizes the colon into this mesenteric window at the distal ileum level. The second technique was described by Deloyers and involves a 180-degree rotation of the right colon by dissecting the right colon attachment and the hepatocolic ligament. The cecum and the ileocecal valve are placed in the right upper quadrant, and the distal colon is mobilized into the pelvis. RESULTS: We included 13 patients, 12 boys and 1 girl. Eight patients had previous surgeries in another hospital: five had an initial transverse colostomy, and three had an ileostomy. The remaining five had the initial operation in our hospital: two had an ileostomy, two had a colostomy, and one had a primary pull-through. The median age at pull-through was 16 months (4-59 months). We used the Turnbull technique in four patients whose aganglionosis was limited to the middle transverse colon. The Deloyers technique was used in the remaining patients, with ganglion cells in the proximal transverse colon. We left a protective ileostomy in five patients. The median follow-up was 4.5 years (3 months to 10 years). The stoma takedown is pending in one patient. CONCLUSION: The Turnbull and Deloyers techniques were helpful in patients with aganglionosis affecting the transverse colon.

Usefulness of a long hood for the detection of bleeding sites in colonic diverticular hemorrhage: A randomized controlled trial.

Background and Aim: The use of a hood at the tip of a colonoscope enables aspiration, inversion of the diverticulum, and observation of the inside of the diverticulum. In most previous studies, a short hood was used; however, observation of the diverticulum is often inadequate. Long food is promising by previous research, but it was a retrospective study using propensity matching and has some limitations. We compared the identification rate of stigmata of recent hemorrhage (SRH) between the long and standard hoods in cases of suspected colonic diverticular hemorrhage (CDH) to confirm the usefulness of long hood by prospective randomized controlled trial. Methods: Eighty patients (42 in the long hood group [L group] and 38 in the short hood group [S group]) who visited the Saitama Medical University Hospital and Tokai University Hachioji Hospital between December 2018 and July 2021 with a chief complaint of bloody stool and suspected CDH, based on the clinical course and imaging studies, were included. Patients were randomly assigned to the L or S group. Results: Regarding patient background, age was significantly higher in the L group; however, no significant differences were found in medical history or history of antithrombotic medication or nonsteroidal anti-inflammatory drug use. Identification rate of SRH was significantly higher in the L group (58.5%, 24/42 patients) than in the S group (26.3%, 10/38 patients) (P < 0.05). All patients were treated using the clip method, and the rate of rebleeding within 1 month was not significantly different between the two groups. Conclusion: A long hood was more useful compared with a short hood in identifying SRH of CDH (UMIN000034603).