Clinical Case Summary

A 33-year-old female patient was referred to the emergency after a polytrauma. CT scan showed a fracture of the pelvis as well as rupture of the anteroinferior wall of the urinary bladder. Conservative treatment of the bladder injury with indwelling urinary catheter was indicated and an orthopedic surgery was performed. During the immediate postoperative period, the patient had urine leaking through the suprapubic surgical wound. A second surgery was indicated by the Urology team, who sutured bladder injury. After 3 days, high volume of urine leaked through the surgical wound (2,5 L per day). A bilateral ureteral catheter was inserted to divert urinary flow but without improvement. The endoscopy team was asked to assess the possibility of vacuum therapy. Flexible cystoscopy jointly conducted by the urology and endoscopy teams identified a fistula in the right anterior wall of the bladder that communicated with surgical wound dehiscence. A Teflon guide wire was passed through the fistula and exteriorized through the skin orifice. A size 12 urethral tube was passed through the guide wire and the urethra, with the distal end externalized through the skin wound. The tube was adapted with fenestrated film (modified vacuum therapy) and a thread (2-0 Ethibond) was left at the distal end to serve as a guide for future changes. Under direct vision, the catheter was pulled and placed in the fistulous tract. An occlusive dressing was applied to the surgical wound and a functioning vacuum was achieved. The indwelling urinary catheter and antibiotic therapy were continued during treatment. A reduction in urine output through the surgical wound was observed. The catheter was changed once a week guided by cystoscopy using the thread left during the first procedure. Two changes were made, with a total treatment duration of 21 days. The urine output from the surgical wound had ceased completely. The control tomography showed complete closure, with no contrast extravasation.

Clinical Case Summary

A 46-year-old man from Bolivia consulted for abdominal pain with watery diarrhoea and occasional rectorrhagia for the last 2 months, associated with asthenia and weight loss. Laboratory tests showed microcytic anaemia, elevated C-reactive protein, positive faecal occult blood and negative stool culture. Colonoscopy (Images 1, 2) revealed deep ulcers in the ileum and colon with discontinuous areas of respected mucosa. Treatment was started with oral methylprednisolone at a dose of 1 mg/kg, with a decrease in the stool rhythm. He returned to the emergency department due to worsening abdominal pain, and was admitted for follow-up care. Histology (Image 3) showed epithelioid granulomas of probable infectious origin, due to the intramacrophagic inclusions, so the corticosteroid treatment was suspended. The quick test for HIV was positive, with a viral load of 79,000 copies/ml and a CD4 count of 88 CD4/ml. Mantoux and IGRA were negative. PCR amplification for Histoplasma spp in ileal biopsy was positive. Amphotericin B was prescribed with prophylaxis of opportunistic infections with trimethoprim-sulfamethoxazole. After 2 weeks, antiretroviral treatment was started. The patient improved, the abdominal pain disappeared and his intestinal rhythm normalised, and he was discharged from hospital. On outpatient follow-up, he was asymptomatic, with resolution of the ulcers in the control colonoscopy and no evidence of fungal structures in the histological examination.
The infection by Histoplasma capsulatum is the most frequent endemic mycosis in the American continent. Intestinal involvement is rare, with a preference for the ileocecal region in the form of deep ulcers that can simulate an outbreak of Crohn disease, as in our case. The use of immunosuppressants, especially anti-TNF-alpha, may worsen its course, highlighting the importance of a broad differential diagnosis, taking into account the patient's epidemiological characteristics.

References

Image 1. Colonoscopy. Terminal ileum with large ulcer with fibrin background, oedema and perilesional erythema.
Image 2. Colonoscopy. Transverse colon with two large deep ulcers with fibrin background and raised edges.
Image 3. Biopsy of ileum. Non-caseating epithelioid granulomas with intramacrophagic inclusions in ileal tissue. HE 40x.

Introduction

Sessile serrated lesions (SSLs), alongside adenomas, play a significant role in the development of colorectal cancer (CRC). Recent studies suggest that the adenoma detection rate (ADR) alone may not be sufficient for predicting post-colonoscopy CRC. Consequently, the ASGE/ACG Quality Task Force has recently recommended the sessile serrated lesion detection rate (SSLDR) as a new priority indicator for colonoscopy quality. Reviewing the variability of SSLDR in the control groups of previous randomized controlled trials (RCTs) may help identify factors that influence study outcomes.

Aims & Methods

A systematic review was conducted using PubMed, Embase, and the Cochrane Library databases to collect data from control groups of RCTs that assessed methods for increasing polyp detection with high-definition white-light colonoscopy (up to March 14, 2025). Random-effects meta-analysis pooled SSLDRs and their 95% confidence intervals (CIs). Heterogeneity was assessed with the I² statistic. Univariable and multivariable meta-regressions were performed to examine associations between SSLDR and study settings (publication year, sample size, number of centers, study design, and geographic origin), demographics (mean age, male proportion), and technical parameters (type of intervention, proportion of screening colonoscopy, ADR, and withdrawal time). This study was registered in PROSPERO (ID: CRD420251012475).

Results

A total of 23,461 patients from 48 studies were included in the analysis. SSLDR in the control arms ranged from 0.3% to 21.5%, with a pooled value of 4.4% (95% CI: 3.3%-5.8%; I² = 93%). Univariable meta-regression analysis identified patient age (OR 1.112; 95% CI: 1.043-1.186) and gender (OR 1.038; 95% CI: 1.003 to 1.074), geographic origin (OR 2.848; 95% CI: 1.585-5.116 for Europe and OR 4.044; 95% CI: 2.205-7.416 for North America), and ADR in the control arms (OR 1.054; 95% CI: 1.031-1.077) as significant predictors of SSLDR, with sample size (OR 0.999; 95% CI: 0.998-1.000) showing a negative correlation. Other factors, such as publication year, number of study centers (single or multiple), study design (parallel or tandem), type of intervention (imaging or mechanical), proportion of screening colonoscopy, and withdrawal time, had no significant effect. In multivariable meta-regression, RCTs conducted in Europe (OR 2.179; 95% CI: 1.242-3.820) and North America (OR 2.664; 95% CI: 1.550-4.580), as well as ADR in control arms (OR 1.035; 95% CI: 1.006-1.065), remained significant predictors of SSLDR, while sample size (OR 0.998; 95% CI: 0.997-0.999) and proportion of screening colonoscopy (OR 0.991; 95% CI: 0.983-0.998) were negatively correlated with SSLDR.

Conclusion

A high level of variability in SSLDR was found in the control groups of RCTs. Standardization of methodological and technical parameters is essential to improve the generalizability and reproducibility of findings from RCTs and enhance SSL detection in colonoscopy.

Introduction

Personalizing biologic therapies in inflammatory bowel disease (IBD) remains a critical unmet need. Here, we investigated circulating and stool microRNAs (miRNAs) as prognostic markers for treatment response across three biologics - anti-TNF, vedolizumab (VEDO), and ustekinumab (UST) - and explored their relationship with gut microbiome to uncover potential host-microbe predictors of response.

Aims & Methods

This study included 43 IBD patients (mean age 40.4 years, 25.6% female, 20.1% with ulcerative colitis) enrolled in the ILEITIS cohort at National University Hospital, Singapore. The majority had received anti-TNF (n=35), whilst others were given VEDO (n=9), or UST (n=15) therapies. Clinical non-response was defined as disease flare within 48 weeks post-induction, indicated by C-reactive protein >5 mg/L, fecal calprotectin >150 μg/g, or moderate to severe endoscopic inflammation. Baseline serum and stool samples were collected and isolated for miRNA profiling by the ID3EAL^TM PanoramiR microRNA Knowledge Panel (MiRXES) via the QuantStudio5-384-well qPCR system (Applied Biosystems). Fecal microbial communities were assessed via shotgun metagenomic sequencing. Differential expression analysis and Spearman correlation with false discovery rate (FDR) adjustment were performed to explore miRNA–microbe associations and treatment response patterns.

Results

Among 376 paired serum and stool miRNAs analyzed, only six exhibited significant positive correlations, indicating largely compartment-specific expression patterns. Stool miRNAs demonstrated stronger and more numerous correlations with gut microbial taxa (11 significant pairs, FDR < 0.05), whereas serum miRNAs showed no strong associations. Biologic-specific miRNA signatures were identified. Predictive modelling identified top-ranked miRNA with high discriminative performance for treatment response; serum miR-296 and stool miR-134 perfectly predicted VEDO response (AUROC = 1.0); serum miR-146 predicted UST response (AUROC = 1.0); and stool miR-302 robustly predicted anti-TNF response (AUROC = 0.897). Correlation analysis between biologic-responsive miRNA and microbial taxa revealed 12 significant correlations for stool-derived miRNA and 14 for serum-derived miRNA. Notable microbial species involved in these associations include Bacteroides uniformis, Parabacteroides distasonis, Phocaeicola dorei, Clostridium scindens, Streptococcus sanguinis, Bilophila wadsworthia, Hungatella hathewayi, and Clostridium leptum, all taxa implicated in IBD-associated dysbiosis, showed significant correlations (FDR < 0.05).

Conclusion

Stool- and serum-derived miRNAs capture non-overlapping but complementary dimensions of host response to biologic therapy in IBD. There are significant overlaps between host miRNAs and microbiome readouts suggesting plausible links between key microbial responders to therapy and host regulatory miRNAs, especially in the luminal compartment. Our findings highlight the value of integrating compartment-specific miRNA and microbiome profiling to improve precision medicine approaches in IBD.

Introduction

ESD allows en bloc resection of complex colorectal polyps. General anaesthetic (GA) for ESD is standard, requiring routine admission to hospital for monitoring. At our Trust conscious sedation is used preferentially. This study presents clinical outcomes of ESD performed in a high-volume tertiary centre in the UK using this approach.

Aims & Methods

• To evaluate the clinical outcomes of colorectal endoscopic submucosal dissection performed without general anaesthesia in a high-volume UK tertiary centre.
• To assess the feasibility and safety of ESD under conscious sedation or no sedation, with particular focus on rates of en bloc and R0 resection, adverse events, and post-procedural admissions.
• To identify clinical and procedural factors independently associated with incomplete (R1) resection following colorectal ESD.
• To compare outcomes between patients undergoing ESD with GA versus those without
Colorectal ESD procedures performed between 2018-2024 in a single centre in the UK were included. Data was retrospectively collected from the patient records. Multiple logistic regression was performed to identify independent factors associated with incomplete resection.

Results

A total of 147 patients (91 males ; median age 68 years) were included. Most polyps were rectal (100/150, 66.6%). Median polyp diameter was 42.5 mm.
GA was utilised in 13 patients, 80 had sedation alongside analgesia (median dose midazolam=2mg, fentanyl=100mcg) 44 required no IV sedation or analgesia, 8 had analgesia alone (median dose fentanyl 100mcg), 2 had sedation alone (median dose midazolam 0.75mg).
4 patients were admitted to hospital after their procedure and 14 were admitted within 30 days. There were 4 (2.7%) perforations and 7 (4.7%) post polypectomy bleeds (PPB).
Most procedures were complete ESD (109/147, 74.1%), the rest being hybrid ESD. R0 excision was achieved in 70/109 (64.2%) of those who had a complete ESD resection. No residual tissue was seen in patients with an R0 resection who had a subsequent LGI endoscopy (43/70). In those with R1 resection, a site check was undertaken at the same Trust in 59 patients. Residual tissue was seen in 7/59 (12%).
On univariate binomial regression, R1 resection was associated with polyps involving the dentate line [OR = 5.29 (95% CI = 1.84 – 17.8)], those with severe fibrosis [OR = 20.8 (95% CI = 3.85- 386.4)] and those receiving a GA [OR = 3.56 (95% CI = 1.06-16.3)]. On multivariate analysis, polyps involving the dentate line [OR = 8.17 (95% CI = 2.24 – 35.8)] and those with severe fibrosis [OR = 17.9 (95% CI = 2.57- 366.2)].

Table 1 - Outcomes of admissions following ESD

Conclusion

ESD is an effective treatment for high-risk complex colorectal polyps, able to provide high rates of en bloc resection. It can be achieved safely in most patients without GA. GA was associated with a higher rate of R1, however, this likely relates to these lesions being more complex.

Introduction

Pancreatic exocrine insufficiency (PEI) is seen in primary pancreatic disease, but has also been seen in extrapancreatic conditions including celiac disease (CeD). The symptoms of PEI and CeD often overlap, which makes differential diagnosis challenging.

Aims & Methods

We aimed to investigate the prevalence of PEI in CeD in a systematic review and meta-analysis.
We searched five databases: PubMed, Embase, Cochrane, Web of Science Core Collection, and Google Scholar, up until October 21, 2024. The pooled prevalence of PEI in biopsy-confirmed CeD was estimated. The quality of studies was appraised, and results were reported according to the PRISMA guidelines.

Results

We identified and screened the titles and abstracts of 1432 publications, of which 60 were reviewed in full text and 12 were included in the analyses. The overall pooled weighted prevalence of PEI in CeD was 13.5% (95% CI 7.2–21.0). The prevalence was similar among children (14.2%; 95% CI 2.0–32.8) and adults (12.8%; 95% CI 7.8–18.7) with CeD. The prevalence in studies that used secretory testing to define PEI was 13.1% (95% CI 6.4–21.3) and in those requiring digestive tests 17.1% (95% CI 5.8–32.1). The weighted prevalence of PEI was however significantly higher among untreated CeD patients (21.7%) than patients on a gluten-free diet (6.9%) (p=0.03), in both adults and children.

Conclusion

One in eight individuals with CeD may suffer from PEI. The prevalence was particularly high in children with untreated CeD. PEI should be considered in patients who do not respond to a gluten-free diet.

References

1. Dominguez-Muñoz JE, Vujasinovic M, de la Iglesia D, et al. European guidelines for the diagnosis and treatment of pancreatic exocrine insufficiency: UEG, EPC, EDS, ESPEN, ESPGHAN, ESDO, and ESPCG evidence-based recommendations. United European Gastroenterol J 2024.
2. Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J 2017;5:153-199.
3. Vujasinovic M, Tepes B, Volfand J, et al. Exocrine pancreatic insufficiency, MRI of the pancreas and serum nutritional markers in patients with coeliac disease. Postgrad Med J 2015;91:497-500.

Introduction

Alcohol-induced acute gastric injury results from disruption of the mucosal barrier and the induction of inflammatory responses. IL-33, an epithelial-derived alarmin, and its receptor ST2, are increasingly recognized as regulators of mucosal immunity and inflammation. However, the specific role of IL-33/ST2 signaling in the immunopathogenesis of ethanol-induced gastric damage remains insufficiently defined.

Aims & Methods

This study aimed to investigate the contribution of IL-33/ST2 signaling to the development of ethanol-induced acute gastric injury. Acute gastric injury was induced in WT and ST2⁻/⁻ mice by oral administration of 80% ethanol. Gastric damage was assessed macroscopically and histologically. Immune cell profiles, cytokine levels, and markers of inflammasome activity and pyroptosis were analyzed using flow cytometry, ELISA, and qPCR.

Results

Ethanol exposure induced severe gastric injury in WT mice, characterized by extensive ulceration and epithelial disruption, whereas ST2⁻/⁻ mice exhibited markedly reduced damage and preserved mucosal architecture. Flow cytometric analysis of gastric tissue revealed significantly higher number of Ly6G⁺ neutrophils and F4/80⁺ macrophages in ethanol-treated WT mice compared to their ST2⁻/⁻ counterparts. Moreover, ethanol-treated WT mice exhibited a significantly higher number of CXCR4-expressing neutrophils, accompanied by an increased number of neutrophils producing TNF-α, IFN-γ, and IL-1β. Similarly, the number of IL-1β–producing macrophages was markedly elevated in WT mice compared to ST2⁻/⁻ mice. Notably, ethanol-treated WT mice also displayed a higher number of NLRP3⁺ neutrophils and macrophages, indicating enhanced inflammasome engagement. Consistent with these findings, gastric tissue from ethanol-treated WT mice demonstrated increased expression of molecular markers associated with inflammasome activation and pyroptotic cell death. Systemically, WT mice exhibited elevated serum concentrations of Th1/Th17 cytokines (IFN-γ, TNF-α, IL-1β, IL-17), while IL-10 levels remained similarly increased across genotypes, suggesting a preserved anti-inflammatory feedback despite pronounced immune activation.

Conclusion

IL-33/ST2 signaling aggravates ethanol-induced gastric injury by intensifying mucosal inflammation, promoting inflammasome-driven pyroptosis, and enhancing recruitment and activation of inflammatory immune cells. The relative protection observed in ST2⁻/⁻ mice underscores the pathological role of this axis and its potential as a therapeutic target in acute gastric damage.