Introduction

Systemic sclerosis (SSc) is a complex, multisystem disease driven by autoimmunity, vasculopathy, and progressive fibrosis. Gastrointestinal involvement is common, with the small bowel frequently affected. However, small bowel dysfunction often remains undiagnosed due to the non-specific nature of symptoms and the limited availability of objective diagnostic tools. Capsule endoscopy provides a minimally invasive method for assessment of the small bowel mucosa. At our laboratory, we developed a machine learning–based algorithm that uses computer vision techniques to analyze capsule endoscopy images and quantify small bowel motor function.

Aims & Methods

To determine the presence of structural and functional abnormalities of the small bowel in patients with SSc using capsule endoscopy.
We conducted a prospective study of 23 consecutive patients with SSc (22 women; mean age 52 ± 8 years; 8 diffuse and 15 limited cutaneous subtype) and a history of gastrointestinal symptoms, evaluated between June 2021 and June 2024. All participants completed a validated gastrointestinal symptom questionnaire (UCLA GIT 2.0) and underwent capsule endoscopy using the PillCam SB3 system (Medtronic).
Morphological abnormalities of the small bowel were assessed by visual analysis of capsule images. Motor function evaluation was performed using a validated automated algorithm based on neuronal-networks to classify capsule endoscopy images as contractile events (i.e. radial wrinkles), non-contractile patterns (tunnel and wall) or turbid luminal content. Movement between consecutive images was measured using Earth Mover's Distance method. Results in patients were compared to those from a historical cohort of 49 healthy subjects (HS).

Results

Structural abnormalities were identified in 6 patients (26%), all presenting with jejunal angiodysplasias. Notably, all affected patients belonged to the limited cutaneous SSc subset (p = 0.037).
Using automated image analysis to assess motor function, patients with SSc demonstrated a significantly lower proportion of contractile events compared to HS (9 ± 7% vs. 14 ± 7% of all images, p = 0.017). Additionally, they exhibited a higher proportion of images with turbid luminal content (34 ± 19% vs. 25 ± 14%, p = 0.036), indicating impaired clearance of secretions, and a higher proportion of static image sequences (11 ± 7% vs. 8 ± 7%, p = 0.036), suggesting reduced intraluminal movement. When comparing SSc subtypes, patients with diffuse cutaneous SSc exhibited significantly fewer contractile events than those with limited cutaneous SSc (5 ± 5% vs. 12 ± 7%, p = 0.005). No correlation was observed between the severity of digestive symptoms, as assessed by UCLA GIT 2.0 scores, and any objective parameter of small bowel motor function.

Conclusion

Our findings demonstrate that small bowel involvement in SSc can be objectively evaluated through morpho-functional analysis of capsule endoscopy images. This novel, minimally invasive approach may enhance the accuracy of disease phenotyping and support more personalized management of gastrointestinal involvement in SSc.

References

Seguí S, Drozdzal M, Pascual G, Radeva P, Malagelada C, Azpiroz F, Vitrià J. Generic feature learning for wireless capsule endoscopy analysis. Comput Biol Med. 2016 Dec 1;79:163-172.

Introduction

Irritable bowel syndrome (IBS) is a chronic gut-brain disorder that can be responsabil for a variety of uncomfortable gastrointestinal symptoms (laid out in the Rome Criteria) that can reduce quality of life. Although the precise mechanism remains unknown, recent research suggests that an imbalance in intestinal microbiota and a dysfunctional gut-brain axis may be involved in the development of IBS. Because of this, methods to restore the microbiota have been explored as treatment for this condition.

Aims & Methods

Randomized placebo controlled trial 180 patients: active group (probiotic formula, 3g/day- 92, placebo group – 88. men and women aged 24 to 75 who met the Rome IV criteria. One sachet probiotic (3 g) contains 7.5 billion bacteria: Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, Bifidobacterium lactis W52, Lactobacillus paracasei W20 Lactobacillus plantarum W62, Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus salivarius W24. Assessments were made at 4, 8, 12 weeks. All patients agreed to maintain their lifestyle behaviors during their participation in the study. Exclusion criteria: chronic gastrointestinal condition (other than IBS), including inflammatory bowel disease, lactose intolerance, celiac disease, diabetes, neoplasms.Patients have complete weekly data on stool frequency and consistency (Boston scale) and intensity of IBS symptoms (abdominal pain/discomfort, bloating, flatulence/borborygmi, and difficulty defecating) on a Likert scale of 0 (absent) to 7 (severe). Participants completed an IBS-specific quality of life questionnaire (IBS-QoL) at randomization (V1), fallow-up (V2) and at the end of the intervention (V3). Primary endpoint was mean weekly scores of gastrointestinal symptoms. Responders of abdominal pain were defined as subjects who experienced a reduction of at least 30% of the mean daily abdominal score reported at baseline (week 0). Secondary endpoints were the total AUC (W0-W12) of abdominal symptoms (abdominal pain, bloating and flatulence/borborygmi).

Results

​There is a significant reduction in abdominal pain and bloating scores trough all 12 weeks of supplementation versus placebo. A higher overall IBS-QOL score, indicative of better QOL was reported at the end of the intervention (specially for interference with activity P=0.05, body image P=0.040, food avoidance P=0.03)

Conclusion

​The probiotic treatment provides statistically significant and clinically relevant benefits for individuals with IBS. Improves gastrointestinal symptoms and quality of life in IBS patient

References

Rome IV criteria-Rome Foundation

Introduction

It is not clear whether the inverse relationship between colonoscopists’ adenoma detection rate (ADR) and post-colonoscopy colorectal cancer (PCCRC) is seamless or subject to “plateau” effect.

Aims & Methods

Aim of the study was to model the pattern of association between ADR and PCCRC. The present study is a systematic review and meta-analysis of studies published up to December 2024 providing the crude incidence rate of PCCRC according to various colonoscopists’ ADR categories. The primary outcome was calculated as the cumulative incidence of PCCRC at the lowest bound of each ADR category, starting from highest to lowest colonoscopists’ ADR. A restricted cubic spline multilevel metaregression analysis was applied to model the inverse association between ADR and cumulative PCCRC.

Results

After applying selection criteria, 7 studies published in 2020-2024, including 2,178,822 patients were included. All studies were conducted in organized CRC screening programs: 5 studies were set in primary colonoscopy screening, whereas 2 studies assessed FIT+ patients undergoing colonoscopy with two different cut-offs (20 µg Hgb/g and 47 µg Hgb/g feces). Four studies were European, and three studies were conducted in the US. Median patient age ranged from 57 to 65 years (see Table 1).
In primary colonoscopy setting (5 studies with 2,025,296 patients), adjusting for standardized follow-up and standardized CRC risk, cumulative incidence of CRC after colonoscopy showed a marked decrease for each 1-unit increase in ADR up to 27%, with a more gradual decline between 27% and 34%. In absolute numbers, assuming a 10-year follow-up period, CRC after colonoscopy ranged from 258/100,000 at 1% ADR, to 228/100,000 at 27% ADR, and 220/100,000 at 34% ADR, yielding a total decrease of 38 CRC after colonoscopy cases per 100,000 patients in 10 years. Beyond this threshold, according to model-based projections, CRC after colonoscopy would be 212/100,000 at 50% ADR, 207/100,000 at 60% ADR, and 197/100,000 at 80% ADR, yielding only an additional decrease of 8 (ADR 50%), 13 (ADR 60%), and 23 (ADR 80%) CRC after colonoscopy cases per 100,000 patients in 10 years, as compared to ADR 34%. Data remained consistent after excluding the study by Pilonis et al. [1], confirming that CRC after colonoscopy plateaus after 34% ADR. Heterogeneity was low (I²=0%) and the visual inspection of the funnel plot revealed some publication bias possibly leading to overestimate the inverse association between ADR and CRC after colonoscopy.
In the FIT-based setting (2 studies, 153,526 patients), quantitative synthesis was not performed owing to the low number of studies and different FIT thresholds (i.e., ≥20 and ≥47 µg Hb/g feces). Nonetheless, when examining the individual studies, there appears to be a more linear decline in post-colonoscopy CRC risk with increasing ADR.

Conclusion

In primary colonoscopy screening, achieving an ADR of at least 27% is essential. While increasing ADR beyond 27% continues to reduce risk, the benefit plateaus beyond ADR 34%, suggesting limited additional clinical advantage. Of note, the absolute risk reduction in CRC after colonoscopy is overall modest. Additional quality measures could provide a more comprehensive assessment of colonoscopy effectiveness.

References

Pilonis ND, Spychalski P, Kalager M, et al. Adenoma Detection Rates by Physicians and Subsequent Colorectal Cancer Risk. JAMA. Published Online First: 16 December 2024.
Wisse PHA, Erler NS, de Boer SY, et al. Adenoma Detection Rate and Risk for Interval Postcolonoscopy Colorectal Cancer in Fecal Immunochemical Test-Based Screening : A Population-Based Cohort Study. Ann Intern Med. 2022;175:1366–73.
Zorzi M, Antonelli G, Barbiellini Amidei C, et al. Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study. Ann Intern Med. 2023;176:303–10.
Schottinger JE, Jensen CD, Ghai NR, et al. Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer. JAMA. 2022;327:2114–22.
Waldmann E, Penz D, Šinkovec H, et al. Interval cancer after colonoscopy in the Austrian National Screening Programme: influence of physician and patient factors. Gut. 2021;70:1309–17.
Lam AY, Li Y, Gregory DL, et al. Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program. Gastrointest Endosc. 2020;92:355-364.e5.
Polychronidis G, He M-M, Vithayathil M, et al. Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use. Gut. 2024;73:1675–83.

Clinical Case Summary

A 27-year-old male with diarrhea and rectal bleeding was diagnosed with moderate ulcerative colitis (UC) (Montreal: E3, Mayo endoscopic subscore: 2). He was started on mesalazine 4 g/day and oral prednisolone 40 mg/day, with clinical remission after 2 weeks. Prednisolone was successfully tapered off over the course of 8 weeks. He was not taking other medications. After starting therapy, the patient reported intermittent red urine discoloration, without other symptoms or association with respiratory tract infections.
Extensive investigation of hematuria was negative, including ANA, ANCA, anti-dsDNA and anti-GBM antibodies and imaging studies. Urine samples were macroscopically normal, with no red blood cells, casts or crystals. Urethrocystoscopy and urine cytology were unremarkable. Renal biopsy was considered.
The patient remained on mesalazine, with clinical, analytical and endoscopic response. During one episode, he noticed that the urine only became reddish after contact with toilet water disinfected with bleach. After stopping bleach toilet disinfection, there was no recurrence. He was diagnosed with mesalazine induced pseudohematuria and did not undergo further investigation.
Mesalazine is the first-line treatment for mild-to-moderate UC. Although uncommon, nephrotoxicity has been described and may result in urine discoloration or hematuria. Mesalazine is excreted in the urine and, when in contact with sodium hypochlorite (the active component of household bleach), oxidises, resulting in red-brown urine discoloration. Rare cases of patients reporting similar situations have been described in the literature. The role of gastroenterologists in recognizing this phenomenon is crucial, since mesalazine is a widespread efficient drug with an otherwise favorable safety profile. As our case illustrates, knowledge of this harmless reaction is desirable to avoid additional tests and potentially harmful unnecessary interventions, such as renal biopsy.

References

Figure 1 - Reaction between the urine of a patient taking mesalazine and the sodium hypochlorite present in household bleach (1A - before addition of bleach; 1B - after addition of bleach).

Disclosure

No conflict of interest to declare.

Introduction

Approximately 50% of patients with Ulcerative Colitis (UC) suffer from daily symptoms of faecal urgency, significantly impacting their quality of life¹. Treatment in quiescent disease is challenging and the first line treatment, loperamide, is often used with caution due to the side effect of constipation.
Enterosorbents such as Enterosgel provide a potential alternative treatment. Enterosgel is thought to work through the adsorption of small molecules in the gastrointestinal (GI) tract, with minimal or no systemic absorption and metabolism², without causing constipation. Enterosgel has shown clinical effectiveness in reducing urgency in patients with diarrhoea predominant irritable bowel syndrome (IBS-D), suggesting potential therapeutic value in patients with UC³, however the mechanism by which this may occur is unknown.

Aims & Methods

This study aimed to evaluate the in vitro adsorption capacity of Enterosgel for three key inflammatory mediators implicated in UC pathogenesis (IL-1β, MMP9 and TNF-α) to explore its potential as a therapeutic option in this patient group.
Three experimental paradigms were performed by diluting recombinant cytokines and enzymes in water-based Enterosgel solutions. After incubation, gel-free supernatants were harvested to analyse residual levels of metabolite via ELISA to identify the quantity of adsorption by Enterosgel. Conditions were conducted with different:

1. Incubation times (15,30,60,120 min)
2. Metabolite concentrations (5 concentrations ranging from 0 - 3000pg/mL)
3. Gel concentrations (0.056, 0.1125, 0.225g/mL)

Results

Enterosgel demonstrated measurable concentration-dependent adsorption of IL-1β, MMP9 and TNF-α with higher analyte input concentrations resulting in greater absolute adsorption. However for TNF-α adsorption saturated at 1000pg/mL, indicating that Enterosgel may not fully adsorb analytes at levels simulating extreme luminal inflammation. Charcoal consistently resulted in lower residual concentrations, although this did not reach statistical significance on permutation testing (p = 0.14).
In time dependent analysis, Enterosgel induced a rapid initial reduction in cytokine levels within 15 minutes, (IL-1β: 98.7%, MMP9: 99.4%, TNF-α: 95.8% adsorbed) with a plateau by 120 minutes (IL-1β: r²=0.74, MMP9: r²=0.64, TNF-α: r²=0.45). In contrast, charcoal demonstrated a near-linear monotonic decline with a slightly greater concentration adsorbed by 120 minutes (IL-1β: 99.9% vs. 99.8%; MMP9: 99.9% vs. 99.1%; TNF-α: 97.2 vs. 96.3%). Increasing gel concentrations improved adsorption efficiency; however, at the highest gel concentration small amounts of residual cytokines remained (IL-1β: 0.25%, MMP9: 0.28%, TNF-α: 3.5%). Doubling of gel concentration led to an average 30% decrease in residual cytokines.

Conclusion

Our findings suggest that Enterosgel demonstrates excellent adsorption of three key pro-inflammatory cytokines relevant to UC, with the greatest reduction at 1 hour and the highest gel concentration—though less than that achieved by charcoal. Evidence of saturation at high analyte levels suggests a limit to Enterosgel’s binding capacity under conditions simulating severe inflammation. These results highlight Enterosgel's clinical potential, however further validation with biological replicates and clinical studies assessing urgency in treated UC is required.

References

(1) Theresa Hunter Gibble, April N. Naegeli, Michael Grabner, Keith Isenberg, Mingyang Shan, et al. Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn’s disease and ulcerative colitis in the United States. 2023; 63 (23): 10.1186/s12876-023-02675-w.
(2) Howell CA, Mikhalovsky SV, Markaryan EN, Khovanov AV. Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs. Scientific Reports. 2019; 9 (1): 10.1038/s41598-019-42176-z.
(3) Howell CA, Kemppinen A, Allgar V, Dodd M, Knowles CH, Mclaughlin J, et al. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). BMJ; 2022.
(4) Shane O'Sullivan, John F Gilmer, Carols Medina. Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update. Mediators of Inflammation. 2015; 2015 (1): 10.1155/2015/964131.
(5) Qingdong Guan JZ. Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease. Mediators of Inflammation. 2017; 2017 (1): 10.1155/2017/4810258.

Introduction

Endoscopists with baseline adenoma detection rates (ADRs) ≤26% who improve their ADRs significantly reduce their patients’ risk of post-colonoscopy colorectal cancer (PCCRC)¹. The recommended withdrawal time (WT) of 8–9 minutes is associated with higher ADRs; however, it includes time spent on therapeutic interventions, which may overestimate actual inspection time and limit its accuracy as a performance metric².

Aims & Methods

We aimed to determine the corrected withdrawal time (cWT)—defined as WT minus intervention time—required for low-performing endoscopists to achieve ADR thresholds of ≥26 and ≥35.
We prospectively analyzed 1,165 the recorded videos of elective colonoscopies performed by 17 endoscopists at Montreal University Hospital Center (IRB; CER22.013/ CER25.12283). Eligible cases were consecutive adults (≥18 years) undergoing elective colonoscopy. Exclusions were complex resections, sigmoidoscopies, incomplete exams, failed recordings, and procedures by endoscopists with <10 prior cases. A research assistant was present during each procedure and documented all periprocedural metrics in real-time. Endoscopists were stratified as low (ADR ≤25%) or high performers (ADR >25%). The primary outcome was the mean cWT required for low performers to achieve an ADR ≥26%. Secondary outcomes included the cWT needed to reach ADR ≥35% and the incremental impact of each additional minute of cWT on detection metrics. Multivariable generalized estimating equation (GEE) models adjusted for patient demographics, bowel preparation, indication of colonoscopy, time of day/month, CADe use, and endoscopist effect.

Results

Low performers required a mean cWT of 10′58″ to achieve an ADR ≥26%, and 13′51″ to reach ≥35% compared to 4′01″ for high performers. Each additional minute of cWT increased ADR odds by 15.3% for low performers and 5.0% for high performers (P < .001). Similar improvements were observed across all detection metrics (Table 1). For every additional cWT minute, the odds of detecting advanced adenomas increased by 10.1%, sessile serrated lesions (SSLs) by 10.1%, and polyps by 16.5% (all P <  .001). Adenoma and polyp counts increased by 7.5% and 7.9%, respectively. Absolute gains per minute were greater in low performers, with ADR increases exceeding 3% beyond 12 minutes of cWT. After adjusting for covariates, each additional cWT minute was associated with a significant increase in the odds of detection: an increase of 6.5% (P = .002) for adenomas, 9.2% (P < .001) for advanced adenomas, 11.5% (P < .001) for SSLs, and 14.9% (P < 0.01) for polyps. With each additional cWT minute, the adenoma count increased by 7.3% and the polyp count increased by 7.8% (P < .001) (results not shown).

Table 1. Mean Detection Metrics and Their Incremental Increase Per Additional Minute of Corrected Withdrawal Time, Overall and Stratified by High vs Low Performers.

Conclusion

Longer cWT enhanced detection across all metrics, particularly for low performes. These findings support personalized cWT targets based on individual performance rather than uniform WT recommendations.

References

1. Pilonis ND, Spychalski P, Kalager M, et al. Adenoma detection rates by physicians and subsequent colorectal cancer risk. JAMA 2025;333:400–407.
2. Rex DK, Anderson JC, Butterly LF, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2024;100:352–381.

Disclosure

Daniel von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm, and Pentax, and has received consultant or speaker fees from Boston Scientific Inc., ERBE Elektromedizin GmbH, and Pendopharm. Roupen Djinbachian has received speaker fees from Fujifilm. The remaining authors declare that they have no conflict of interest.

Introduction

The integrity of the intestinal barrier is crucial in preventing bacterial translocation and systemic inflammation, both of which contribute to the progression of advanced chronic liver disease (ACLD). While surrogate biomarkers exist, direct real-time assessment of intestinal barrier function has been challenging. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that allows direct visualization of mucosal integrity during endoscopy.

Aims & Methods

The present study aims to determine the prevalence of CLE-detectable barrier dysfunction in ACLD patients, to explore its association with disease severity, and to assess its prognostic significance. In our prospective study, 48 ACLD patients who underwent routine upper gastrointestinal endoscopy between 11/2022 and 04/2024 were examined using CLE (Cellvizio®) in the duodenum following intravenous fluorescein injection (2.5–5 mg). The presence or absence of fluorescein leakage into the intestinal lumen was determined. The presence of leakage in more than three different locations in the duodenum was indicative of intestinal barrier dysfunction. Clinical data including Child-Turcotte-Pugh (CTP) score, MELD score, hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and biomarkers of liver function were recorded. Patients were followed for a median of 13.2 months, with liver-related events (LRE) including first or further decompensation, acute-on-chronic liver failure (ACLF), and liver-related death as endpoints.

Results

Intestinal barrier dysfunction was detected in 52% of patients and was found to be significantly more prevalent in decompensated ACLD compared to compensated ACLD (73% vs. 25%, p=0.021). CLE-based barrier dysfunction correlated with bilirubin (p=0.033) and albumin (p=0.010), but not with HVPG (p=0.314), LSM (p=0.482), or C-reactive protein (p=0.457). Patients exhibiting intestinal barrier dysfunction demonstrated a significantly higher risk of LRE during follow-up (25% vs. 5% at 12 months, 43% vs. 5% at 18 months, log-rank p=0.005). In univariable Cox regression analysis, intestinal barrier dysfunction remained independently associated with LRE (hazard ratio: 2.36, 95% confidence interval: 1.34–84.0, p=0.025). Importantly, the prognostic impact of CLE findings aligned with established risk markers such as MELD and albumin.

Conclusion

CLE provides real-time, high-resolution insight into intestinal barrier integrity in ACLD patients. The strong correlation between CLE-detected barrier dysfunction and adverse clinical outcomes suggests that CLE has the potential to serve as a prognostic instrument for risk stratification. As CLE can be integrated into standard endoscopic procedures, it may provide an accessible and clinically relevant means of assessing intestinal barrier function in routine practice in patients with liver cirrhosis. Further studies in larger cohorts are needed to validate CLE for routine clinical use and to explore therapeutic interventions targeting intestinal barrier dysfunction.

Disclosure

NO CoI to declare