A recent Gastroenterology digest,
as sent to subscribers

Study Type: Narrative review (no systematic search methodology or quantitative synthesis described in the abstract).

Key Question: What are the risk factors for, and how can clinicians prevent and manage, adverse events associated with electrocautery-enhanced lumen-apposing metal stents (EC-LAMS) across their expanding indications?

Key Findings:

• Adverse events occur in up to 1 in 5 patients, limiting uptake outside high-volume referral centres.
• Principal complications are misdeployment (particularly feared), bleeding, peritoneal leak, stent occlusion and migration.
• The review covers indication-specific risk factors and prevention strategies (e.g. pseudocyst/necrosis drainage, gallbladder and bile duct drainage, gastroenterostomy, EDGE for ERCP in RYGB anatomy) plus rescue techniques. Specific effect sizes are not given in the abstract.

Clinical Relevance: As EC-LAMS use extends beyond tertiary pancreatic units, UK endoscopists and commissioners need clear guidance on complication prevention and rescue, particularly for centres considering offering these procedures.

Limitations: Narrative design risks selection bias and offers no pooled estimates, so the "1 in 5" figure and recommended techniques cannot be graded for evidence quality from the abstract alone.

Study Type: Narrative review (no systematic search methodology or pooled analysis described in the abstract).

Key Question: What does current evidence support for preventing incident and recurrent *C. difficile* infection, and how should gastroenterologists apply it in practice?

Key Findings:

• Primary prevention rests on antimicrobial stewardship, infection control, diagnostic stewardship (distinguishing colonisation from true infection), and preserving the microbiome.
• Secondary prevention options reviewed: extended antibiotic regimens, oral vancomycin prophylaxis during later systemic antibiotics, and microbiome restoration (conventional FMT and FDA-approved microbiota-based products).
• Highest-risk groups (older adults, immunocompromised, transplant recipients, IBD) are discussed; emerging approaches include risk stratification, biomarkers, and bile acid modulation. No quantitative effect sizes are given in the abstract.

Clinical Relevance: Offers a framework for recurrence prevention in high-risk patients, though availability of FDA-approved microbiota products and local FMT access differ from UK/NHS practice, so applicability depends on local pathways and NICE/BSG guidance.

Limitations: As a narrative review, it lacks stated search methods or quality appraisal, so selection bias and uneven evidence grading are possible.

Study Type: Retrospective cohort study (single-source, 2011–2021).

Key Question: Do patients with sporadic early-onset CRC (<50 years) have a higher risk of metachronous advanced neoplasia after resection than those with average-onset CRC (≥50 years)?

Key Findings:

• MAN rates were similar between EOCRC (n=230) and AOCRC (n=504): 13% vs 16.1% (p=0.342). MAN-free survival was significantly lower in AOCRC.
• Metachronous non-advanced neoplasia was less frequent in EOCRC (17% vs 26%, p=0.009).
• Older age, smoking, and a distal (descending/sigmoid) index cancer were independently associated with MAN (effect sizes not reported in abstract).

Clinical Relevance: Findings do not support a separate, intensified post-CRC surveillance schedule for younger patients, which is relevant to BSG/ACPGBI/AUGIS post-polypectomy and post-CRC surveillance guidance and endoscopy capacity.

Limitations: Retrospective design with surveillance-dependent ascertainment (EOCRC had shorter time to first endoscopy and longer follow-up), limiting comparability; setting and sample size may restrict generalisability.

Study Type: Clinical practice guideline (AGA/AASLD), based on systematic reviews of six prioritised questions and GRADE methodology.

Key Question: What evidence-based recommendations should guide diagnosis, treatment escalation, symptom control and post-transplant management in adults with PBC?

Key Findings:

• Six recommendations: PBC-specific ANA testing in AMA-negative suspected PBC; UDCA first-line; liver stiffness measurement for prognostication; PPAR agonists for inadequate UDCA response or intolerance; linerixibat for moderate-to-severe pruritus; UDCA prophylaxis after transplantation.
• Certainty of evidence ranged from moderate to very low. The abstract does not report effect sizes, recommendation strengths or specific response criteria.

Clinical Relevance: Provides a US framework for risk-stratified second-line therapy and pruritus management that UK clinicians can compare with BSG/UK-PBC guidance and NICE appraisals. Availability of PPAR agonists and linerixibat in the NHS may differ.

Limitations: Much of the evidence base is low or very low certainty, and the abstract gives no detail on recommendation strength.

Study Type: Mechanistic preclinical study (murine DSS colitis, knockout models, organoids) with a small randomised, placebo-controlled trial in UC patients.

Key Question: Does alginate promote mucosal healing via a microbiota-taurine-epithelial pathway, and is this relevant to ulcerative colitis?

Key Findings:

• In DSS colitis, alginate improved recovery (reduced inflammation, restored barrier function, increased crypt proliferation) by enriching taurine-releasing bacteria (*B. acidifaciens*, *L. murinus*) and raising intestinal taurine. Antibiotics abolished the effect.
• Benefit depended on taurine transport (*Slc6a6*) and epithelial *Cyp2c55* induction; protection was lost in knockout mice and organoids.
• In UC patients receiving antibiotic-primed FMT then alginate or placebo, the primary endpoint was not met. Alginate was associated with higher faecal taurine and colonic CYP2C18 expression, mirroring the preclinical mechanism.

Clinical Relevance: No clinical efficacy is shown, but the findings offer a mechanistic rationale for fibre-based, microbiota-targeted adjuncts in UC.

Limitations: The clinical trial was negative for its primary endpoint, so the biomarker changes are hypothesis-generating only (sample size and effect estimates not reported in the abstract).

Study Type: Preclinical laboratory study (in vitro cell models and immunocompetent mouse models) with a supporting analysis of patient HMGCR expression data.

Key Question: What metabolic changes accompany acquired gemcitabine resistance in pancreatic ductal adenocarcinoma, and can they be therapeutically exploited?

Key Findings:

• Resistant cells suppressed pyrimidine salvage, creating dependence on mevalonate biosynthesis and marked sensitivity to statins.
• Statins selectively inhibited growth of gemcitabine-resistant tumours in mice; geranylgeranyl pyrophosphate depletion, not cholesterol limitation, mediated this effect.
• HMGCR expression fell progressively as resistance developed, and low expression predicted poorer response to gemcitabine-based therapy in patients. Effect sizes were not reported in the abstract.

Clinical Relevance: Statins are cheap and widely used in the NHS, so this hypothesis-generating work could inform trials of statin repurposing or HMGCR-based stratification in PDAC, where treatment options after resistance are limited.

Limitations: Findings are preclinical; the patient data are an expression-based association only, with no evidence yet that statins improve outcomes in gemcitabine-resistant disease.

Study Type: Randomised crossover trial (two-period, two-sequence; n=29)

Key Question: Can a Tasty&Healthy (T&H) diet reduce fecal calprotectin (FC) in first-degree relatives of Crohn's disease patients who have persistently raised FC but no diagnostic evidence of CD?

Key Findings:

• At week 8, median FC was 64 μg/g on T&H vs 112 μg/g on habitual diet (P=.022); ≥50% FC reduction occurred in 71% vs 27% (RR 2.68, 95% CI 1.09–6.60).
• Across both periods, T&H lowered FC by 37% relative to habitual diet (ratio 0.63, 95% CI 0.51–0.80; P<0.001).
• Six microbial species differed between diets; 83% had good or complete adherence and 79% rated the diet acceptable.

Clinical Relevance: Suggests subclinical intestinal inflammation in at-risk relatives is diet-modifiable, informing future CD prevention strategies, though not yet practice-changing for UK clinics.

Limitations: Small sample, short 8-week periods, and a surrogate endpoint (FC) mean the effect on progression to CD remains unknown.

Study Type: Mixed translational study: observational patient cohort (HCC, cirrhosis, healthy controls) combined with mechanistic experiments in four autochthonous murine HCC models and cell-based assays.

Key Question: Does intestinal *Candida albicans* drive HCC progression and resistance to anti-PD-1 therapy, and by what mechanism?

Key Findings:

• In patients, faecal *C. albicans* was higher in HCC and associated with advanced disease, shorter overall survival, and reduced durable clinical benefit (effect sizes not reported in abstract).
• In mice, *C. albicans* gavage increased tumour burden via an IL-17A-driven axis inducing immunosuppressive Trem2+ macrophages and impaired CD8+ T cell function; IL-17A blockade or deficiency largely abolished this effect.
• *C. albicans* impaired anti-PD-1 efficacy in vivo; antifungal treatment partially restored response.

Clinical Relevance: Faecal *C. albicans* may become a biomarker or combination-therapy target for ICI-treated HCC, though no UK clinical application exists yet.

Limitations: Human associations come from modest observational cohorts, and the antifungal intervention was proof-of-concept in mice only, so causality in patients is unproven.