An overview on recent approaches for colonic drug delivery systems.

Colon-targeted drug delivery systems have garnered significant interest as potential solutions for delivering various medications susceptible to acidic and catalytic degradation in the gastrointestinal (GI) tract or as a means of treating colonic diseases naturally with fewer overall side effects. The increasing demand for patient-friendly drug administration underscores the importance of colonic drug delivery, particularly through noninvasive methods like nanoparticulate drug delivery technologies. Such systems offer improved patient compliance, cost reduction, and therapeutic advantages. This study places particular emphasis on formulations and discusses recent advancements in various methods for designing colon-targeted drug delivery systems and their medicinal applications.

Screening of normal endoscopic large bowel biopsies with interpretable graph learning: a retrospective study.

OBJECTIVE: To develop an interpretable artificial intelligence algorithm to rule out normal large bowel endoscopic biopsies, saving pathologist resources and helping with early diagnosis. DESIGN: A graph neural network was developed incorporating pathologist domain knowledge to classify 6591 whole-slides images (WSIs) of endoscopic large bowel biopsies from 3291 patients (approximately 54% female, 46% male) as normal or abnormal (non-neoplastic and neoplastic) using clinically driven interpretable features. One UK National Health Service (NHS) site was used for model training and internal validation. External validation was conducted on data from two other NHS sites and one Portuguese site. RESULTS: Model training and internal validation were performed on 5054 WSIs of 2080 patients resulting in an area under the curve-receiver operating characteristic (AUC-ROC) of 0.98 (SD=0.004) and AUC-precision-recall (PR) of 0.98 (SD=0.003). The performance of the model, named Interpretable Gland-Graphs using a Neural Aggregator (IGUANA), was consistent in testing over 1537 WSIs of 1211 patients from three independent external datasets with mean AUC-ROC=0.97 (SD=0.007) and AUC-PR=0.97 (SD=0.005). At a high sensitivity threshold of 99%, the proposed model can reduce the number of normal slides to be reviewed by a pathologist by approximately 55%. IGUANA also provides an explainable output highlighting potential abnormalities in a WSI in the form of a heatmap as well as numerical values associating the model prediction with various histological features. CONCLUSION: The model achieved consistently high accuracy showing its potential in optimising increasingly scarce pathologist resources. Explainable predictions can guide pathologists in their diagnostic decision-making and help boost their confidence in the algorithm, paving the way for its future clinical adoption.

Abnormal gastrointestinal motility is a major factor in explaining symptoms and a potential therapeutic target in patients with disorders of gut-brain interaction.

The objective of this article is to review the evidence of abnormal gastrointestinal (GI) tract motor functions in the context of disorders of gut-brain interaction (DGBI). These include abnormalities of oesophageal motility, gastric emptying, gastric accommodation, colonic transit, colonic motility, colonic volume and rectal evacuation. For each section regarding GI motor dysfunction, the article describes the preferred methods and the documented motor dysfunctions in DGBI based on those methods. The predominantly non-invasive measurements of gut motility as well as therapeutic interventions directed to abnormalities of motility suggest that such measurements are to be considered in patients with DGBI not responding to first-line approaches to behavioural or empirical dietary or pharmacological treatment.

Recent development in fabrication and evaluation of phenolic-dietary fiber composites for potential treatment of colonic diseases.

Phenolics have been shown by in vitro and animal studies to have multiple pharmacological effects against various colonic diseases. However, their efficacy against colonic diseases, such as inflammatory bowel diseases, Crohn's disease, and colorectal cancer, is significantly compromised due to their chemical instability and susceptibility to modification along the gastrointestinal tract (GIT) before reaching the colonic site. Dietary fibers are promising candidates that can form phenolic-dietary fiber composites (PDC) to carry phenolics to the colon, as they are natural polysaccharides that are non-digestible in the upper intestinal tract but can be partially or fully degradable by gut microbiota in the colon, triggering the release at this targeted site. In addition, soluble and fermentable dietary fibers confer additional health benefits as prebiotics when used in the PDC fabrication, and the possibility of synergistic relationship between phenolics and fibers in alleviating the disease conditions. The functionalities of PDC need to be characterized in terms of their particle characteristics, molecular interactions, release profiles in simulated digestion and colonic fermentation to fully understand the metabolic fate and health benefits. This review examines recent advancements regarding the approaches for fabrication, characterization, and evaluation of PDC in in vitro conditions.

Association between irritable bowel syndrome and micronutrients: A systematic review.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut brain interaction with a multifactorial etiology. Food trigger avoidance is common among individuals with IBS and exclusion diets are gaining popularity. However, recent guidelines on IBS management cautioned regarding the use of unsupervised dietary therapy with concerns of development of poor eating habits and even nutritional deficiencies. We aimed to review the available literature on the effect of habitual and exclusion diets on micronutrient status as well as the role of micronutrient supplementation in alleviating IBS symptoms. METHODS: Four electronic databases (PubMed, Embase, Cochrane, Web of Science) were searched for articles that reported micronutrient data in patients with IBS. Serum micronutrient levels and dietary intake of micronutrients in patients with IBS were collected. The extracted data were tabulated and organized by micronutrient type to observe for trends. RESULTS: Twenty-six articles were included in this systematic review (12 interventional and 14 observational studies). Studies showed that generally IBS subjects had lower levels of vitamin B2, vitamin D, calcium, and iron at baseline compared with non-IBS subjects. Studies also found that exclusion diets were associated with lower intake of micronutrients especially vitamin B1, B2, calcium, iron, and zinc. There was a lack of interventional studies on micronutrients. CONCLUSION: Irritable bowel syndrome patients are at risk of developing multiple micronutrient deficiencies that may have both localized gastrointestinal as well as systemic effects. Dietary management of IBS patients should include a proper dietitian review to ensure nutritional adequacy where possible.

Impact of aspirin discontinuation on thrombotic complications in laparoscopic colorectal cancer surgery.

BACKGROUND: The number of patients taking antiplatelet therapy is increasing. However, there is no definitive guideline for the perioperative management of antiplatelet therapy. Conventionally, the discontinuation of antiplatelet drugs has been the basic treatment as perioperative management. Therefore, we investigated the risk of discontinuing aspirin concerning thrombotic complications in laparoscopic colorectal cancer surgery. METHODS: Between January 2015 and December 2019, a total of 729 patients underwent laparoscopic colorectal cancer surgery in Toyonaka Municipal Hospital. Sixty-four patients taking antithrombotic drugs aside from aspirin were excluded from this study; the remaining 665 patients were considered eligible and divided into three groups. The patients not taking aspirin were classified as the "Control group" (n = 588). Among the patients taking aspirin, those who continued preoperative aspirin were classified as the "Aspirin group" (n = 30), and those who discontinued preoperative aspirin were classified as the "No-aspirin group" (n = 47). The Aspirin, No-aspirin, and Control groups were compared retrospectively. RESULT: Among the 3 groups, there were no significant difference in operative time (p = 0.14), bleeding volume (p = 0.63), or postoperative hospital stay (p = 0.06). Assessing the postoperative complication, bleeding complications were significantly more frequent in the Aspirin group (p < 0.01), although those complications were all Clavien-Dindo grade II. In contrast, thrombotic complications were significantly more frequent in the No-aspirin group (p < 0.01). Note that those complications were all Clavien-Dindo Grade III/IV. This result suggested that discontinuing aspirin increased the risk of severe thrombotic complication. CONCLUSION: Discontinuation of aspirin as perioperative management in laparoscopic colorectal cancer surgery increased the risk of severe thrombotic complications.

Prevalence of Pelvic Floor Disorders in the Fibromyalgia Population: A Systematic Review.

This study aimed to review the literature to establish the prevalence of pelvic floor disorders in the fibromyalgia population. A systematic literature search through computerized databases including PubMed and EMBASE was completed using medical subject heading (MeSH) terms from January 1, 1990 to November 1, 2017. Articles were included if the focus was prevalence of pelvic floor disorders in the population of persons with fibromyalgia. To provide consistency of diagnosis, use of the American College of Rheumatology 1990 or 2010 criteria was required. Evidence was graded according to Canadian Task Force on Preventive Health Care and Newcastle-Ottawa quality assessment scales. A total of 11 studies were deemed eligible for inclusion from 1024 articles initially identified. Only one study used the most recent 2010 American College of Rheumatology diagnostic criteria. There was significant heterogeneity in the reporting of fibromyalgia populations. Outcomes reported were variable and not consistent across studies; thus, data could not be pooled. There appears to be a high prevalence of gastrointestinal, genitourinary, and gynaecological dysfunction. In case-control studies, these dysfunctions appeared to be more prevalent in the fibromyalgia group than in the control populations. However, this difference could not be quantified more specifically. In conclusion, the small number of eligible studies and the variety of pelvic floor outcomes reported limited formation of conclusive prevalence of pelvic floor disorders in the fibromyalgia population. From the small number of studied patients, there may be a higher prevalence of gastrointestinal, genitourinary, and gynaecological concerns in women with fibromyalgia.

Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.

BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis. CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT. RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI. CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.

Nationwide Survey for Application of ROME IV Criteria and Clinical Practice for Functional Constipation in Children.

BACKGROUND: This study aimed to investigate the awareness and application of ROME IV criteria for functional constipation (FC) in real-world practices and assessed differences between pediatric gastroenterologists (PGs) and general pediatricians. METHODS: A total of 239 (47.8%) out of 500 nationwide pediatricians answered a questionnaire for diagnosis and management of pediatric FC; 60 were PGs (75% of total PGs in Korea). RESULTS: A total of 16.6% of pediatricians were aware of the exact ROME IV criteria. Perianal examination and digital rectal examination were practiced less, with a higher tendency among PGs (P < 0.001). Treatment duration was longer among PGs for > 6 months (63.8%) than < 3 months among general pediatricians (59.2%, P < 0.001). Fecal disimpaction and rectal enema were practiced among 78.8% and 58.5% of pediatricians, respectively. High dose medication for initial treatment phase was prescribed by 70.7% of pediatricians, primarily within the first 2 weeks (48.3%). The most commonly prescribed medications in children aged > 1-year were lactulose (59.1%), followed by polyethylene glycol (PEG) 4000 (17.7%), and probiotics (11.8%). Prescription priority significantly differed between PGs and general pediatricians; lactulose or PEG 4000 were most commonly prescribed by PGs (89.7%), and lactulose or probiotics (75.7%) were prescribed by general pediatricians (P < 0.001). For patients aged < 1-year, lactulose (41.6%) and changing formula (31.7%) were commonly prescribed. Most participants recommended diet modification, and PGs more frequently used defecation diary (P = 0.002). CONCLUSION: Discrepancies between actual practice and Rome IV criteria and between PGs and general pediatricians were observed. This survey may help construct practice guidelines and educational programs for pediatric FC.

[Management of functional bowel disorders]. / Traitement des troubles fonctionnels intestinaux.

Management of functional bowel disorders. The better knowledge of irritable bowel syndrome (IBS) and functional bloating pathogenic mechanisms led to an increase of the possible therapeutic options, which are somewhat different, in IBS, between IBS-D and IBS-C Besides routine options (antispasmodics, alverine, laxatives, loperamide), low-dose antidepressants and non-pharmaceutical options are now recognized as validated and effective therapeutic choices. In addition, dietary advices (particularly indication of a low FODMAPs diet) and treatments acting on gut microbiota (probiotics, antibiotics) are more and more discussed and indicated. In functional bloating, treatment remains empirical. Dietary modifications, simeticone, prokinetics, low-dose antidepressants and microbiome modulation can be proposed.

Traitement des troubles fonctionnels intestinaux. Les progrès effectués dans la compréhension de la physiopathologie du syndrome de l'intestin irritable (SII) mais aussi du ballonnement fonctionnel ont conduit à une diversification des solutions thérapeutiques potentielles. Dans le SII, celles-ci sont fonction du sous-type de syndrome, diarrhéique et avec constipation. À côté des médicaments classiques (antispasmodiques, alvérine, laxatifs, lopéramide), les antidépresseurs à faibles doses et les alternatives non médicamenteuses trouvent désormais une place. Surtout, l'utilité d'un régime, notamment appauvri en FODMAP, et les solutions visant à agir sur la flore (probiotiques, antibiotiques) sont de plus en plus discutées. Dans le ballonnement fonctionnel, la prise en charge demeure empirique. Conseils diététiques, prokinétiques, antidépresseurs à faibles doses et agents actifs sur la flore peuvent être testés.

Raf kinase inhibitor protein mediates intestinal epithelial cell apoptosis and promotes IBDs in humans and mice.

OBJECTIVE: Raf kinase inhibitor protein (RKIP) appears to control cancer cell metastasis and its expression in colonic tissue is related to colonic cancer development. We sought to identify the roles of RKIP in maintaining homeostasis of GI tract. DESIGN: The expression of RKIP was determined by immunohistochemistry and western blot analysis. RKIP knockout and wild-type mice were administered dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis, and the mice were assessed based on colitis symptoms and biochemical approaches. The mechanism was analysed using immunoprecipitation and pull-down experiments. RESULTS: The RKIP expression is positively correlated with the severity of IBD. RKIP deficiency protects mice from DSS-induced or TNBS-induced colitis and accelerated recovery from colitis. RKIP deficiency inhibits DSS-induced infiltration of acute-phase immune cells and reduces production of proinflammatory cytokines and chemokines in colon. RKIP deficiency inhibits DSS-induced or TNBS-induced colonic epithelial barrier damage and intestinal epithelial cell (IEC) apoptosis. RKIP deficiency also inhibits tumour necrosis factor-alpha-induced IEC apoptosis and colitis. Mechanistically, RKIP enhances the induction of P53-upregulated modulator of apoptosis by interacting with TGF-ß-activated kinase 1 (TAK1) and promoting TAK1-mediated NF-κB activation. This is supported by the observation that TAK1 activation is positively correlated with the expression of RKIP in human clinical samples and the development of IBD. CONCLUSIONS: RKIP contributes to colitis development by promoting inflammation and mediating IEC apoptosis and might represent a therapeutic target of IBD.

Design and validation of a German version of the GSRS-IBS - an analysis of its psychometric quality and factorial structure.

BACKGROUND: Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. METHODS: This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). RESULTS: The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach's Alpha between .77 and .92), and for all subscales (Cronbach's Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p < .01) and the anxiety (r = .42; p < .01) and depression scales (r = .43; p < .01) of the HADS-D. CONCLUSION: The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies.

Limited evidence of abnormal intra-colonic pressure profiles in diverticular disease - a systematic review.

AIM: Abnormal colonic pressure profiles and high intraluminal pressures are postulated to contribute to the formation of sigmoid colon diverticulosis and the pathophysiology of diverticular disease. This study aimed to review evidence for abnormal colonic pressure profiles in diverticulosis. METHOD: All published studies investigating colonic pressure in patients with diverticulosis were searched in three databases (Medline, Embase, Scopus). No language restrictions were applied. Any manometry studies in which patients with diverticulosis were compared with controls were included. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies was used as a measure of risk of bias. A cut-off of five or more points on the NOS (fair quality in terms of risk of bias) was chosen for inclusion in the meta-analysis. RESULTS: Ten studies (published 1962-2005) met the inclusion criteria. The studies followed a wide variety of protocols and all used low-resolution manometry (sensor spacing range 7.5-15 cm). Six studies compared intra-sigmoid pressure, with five of six showing higher pressure in diverticulosis vs controls, but only two reached statistical significance. A meta-analysis was not performed as only two studies were above the cut-off and these did not have comparable outcomes. CONCLUSION: This systematic review of manometry data shows that evidence for abnormal pressure in the sigmoid colon in patients with diverticulosis is weak. Existing studies utilized inconsistent methodology, showed heterogeneous results and are of limited quality. Higher quality studies using modern manometric techniques and standardized reporting methods are needed to clarify the role of colonic pressure in diverticulosis.

Intracorporeal ileocolic anastomosis in patients with laparoscopic right hemicolectomy.

BACKGROUND: Since the introduction of laparoscopic colorectal surgery, there has been a controversy between creating an intracorporeal or extracorporeal ileocolic anastomosis in right hemicolectomy. The purpose is to report our experience in intracorporeal anastomosis following right hemicolectomy in both malignant and benign pathologies. STUDY DESIGN: A retrospective review of a prospectively collected database was conducted at Virgen de la Arrixaca Clinical University Hospital (Murcia) between January 2000 and April 2014. The study includes all surgery patients who received a laparoscopic right hemicolectomy with an intracorporeal ileocolic anastomosis. The criteria for exclusion were conversion to open surgery during the procedure due to technical difficulties during dissect. Tumours considered T4 were not excluded, nor were stage IV patients or those with a history of previous abdominal surgery. RESULTS: There were 173 patients (63 females) aged 67 (range 14-91) years, with body mass index of 27 (17-52) kg/m(2) and ASA 1:2:3:4 of 12:78:68:15; 41% had previous abdominal surgery and 70% had a pre-existing comorbidity. Operating time was 142 (60-270) min. Specimen extraction site incision length was 8.1 (6-11.1) cm. Conversion rate was 9.2%, and there were 39 complications (22.54%) and 9 reoperations (5.2%). Readmission rate was 5.2%. Length of stay was 5.7 (1-35) days. CONCLUSION: The intracorporeal procedure is a safe and feasible alternative for creating an ileocolic anastomosis. It involves a similar rate of complications and may prevent some of the drawbacks presented by extracorporeal anastomosis.