Introduction

Serrated polyps (SPs) are precursors to 15–20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence.

Aims & Methods

Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps. We systematically searched PubMed, EMBASE, and Cochrane for cohort, case-control studies, and clinical trials from inception to Dec 31, 2023, for CRC or advanced polyps [advanced adenoma (AA) or advanced SP] incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. CRC and advanced polyp incidence per 1,000 person-years (p-y) were estimated. We performed a meta-analysis by calculating pooled relative risks (RR) using a random-effects model.

Results

5,903 studies were reviewed and 14 included, with 493,949 patients (mean age 59·5 years, 55% men). Mean follow-up was 4·9 years. CRC incidence per 1,000 p-y was 2·09 (95%CI 1·29–2·90) for advanced SP, 1·52 (0·78–2·25) for SP>10mm, 5·86 (2·16–9·56) for SP with dysplasia, 1·18 (0·77–1·60) for proximal SP, 0·52 (0·08–1·12) for >3SP, 0·50 (0·35–0·66) for non-advanced SP, and 0·44 (0·41–0·46) for normal colonoscopy. Metachronous CRC risk was higher in advanced SP vs non-advanced SP (RR 1·84, 95%CI 1·11–3·04), and vs normal colonoscopy (RR 2·92, 2·26–3·77); in SP>10mm vs <10mm (RR 2·61, 1·43–4·77), and vs normal colonoscopy (RR 3·52, 2·17–5·69); and in SP with dysplasia vs normal colonoscopy (RR 2·71, 2·00–3·67). No increase in CRC or advanced polyp risk was found in patients with proximal vs distal SP, nor in >3SP vs 1–2SP.

Conclusion

CRC risk is significantly higher in patients with baseline advanced SP after 4·9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SP.

Disclosure

RJ has received research grants from MSD, and has participated as an advisor to MSD, Norgine, Alpha-Sigma, and GISupply. UL has participated in the advisory board (UniversalDx, Lean Medical, Vivante, Kohler Ventures), and as consultant (Medtronic, Clinical Genomics, Guardant Health, Freenome, ChekCap). MDR has no COI since start of 2020 (Advisor for Norgine in 2019). The rest of authors have nothing to disclose.

Introduction

Crohn's disease (CD) is a heterogeneous condition with potentially complicated course. We aimed to evaluate the rates and risk factors for complicated disease course within a real-world, prospective inception cohort of patients with newly diagnosed CD (ndCD).

Aims & Methods

This prospective, longitudinal cohort study included adults with ndCD managed at a tertiary referral center. Treatment decisions were made at the discretion of the treating physician. The key outcomes were: (1) complicated-disease course - defined as CD-related hospitalization, surgery, steroid dependency, or the use of ≥2 biologics; (2) extra-complicated disease course - defined as recurrent or prolonged hospitalization (>5 days), multiple perianal procedures, intestinal resection, steroid dependency, or the use of ≥3 biologics; and (3) phenotype progression. Kaplan-Meier survival analysis was used to assess rates of complicated course over 5 years, and multivariable Cox regression models were applied to identify baseline risk factors.

Results

A total of 192 patients with ndCD were enrolled; 70% presented with an inflammatory phenotype (B1) (see Table 1). Overall, 150 patients (78.1%) were recommended to start biologic therapy, with half receiving this recommendation within 4.1 months (95% CI: 2.1-6.3) from diagnosis. Of these, 134 patients (89.3%) initiated treatment - 50% within 6 months and 63.6% within 12 months. Cumulative outcome rates at 1, 3, and 5 years post-diagnosis were: complicated course - 24.2%, 35.9%, and 51.3%, respectively; extra-complicated course - 15.6%, 20.5%, and 29.0%, respectively; phenotype progression - 1.6%, 5.5%, and 10.6%, respectively. In a multivariable analysis, patients with a progressive phenotype (B2/B3) at diagnosis had significantly increased risk for complicated (HR 3.3, 95% CI:2.0-5.7) and extra-complicated (HR 6.7, 95% CI:3.1-14.4) disease course. Additional risk factors included elevated inflammatory markers and disease extent at diagnosis. We further analysed the subgroup of 33 patients with a B1 phenotype (~25% of those with a B1 phenotype) who were not recommended biologic therapy by their treating physician. In this subgroup, the complicated course was markedly low, 3.0%, 6.3%, and 11.5% at 1, 3, and 5 years, respectively, and none developed an extra-complicated course. Notably, this subgroup exhibited significantly lower inflammatory indices (CDAI, HBI, CRP, and fecal calprotectin) at diagnosis compared to patients for whom biologics were recommended (all p<0.001).

Table 1:

Conclusion

In this real-world cohort, applying a best-practice treatment approach, over half of patients with ndCD experienced a complicated course within five years, primarily those with a progressive phenotype at diagnosis. Notably, a subset of patients with an inflammatory phenotype and low inflammatory burden had favorable long-term outcomes without biologics, underscoring the importance of early risk stratification to guide individualized treatment strategies.

Introduction

Hyperbaric oxygen therapy (HBOT) is a treatment that delivers 100% oxygen in a pressurized chamber. HBOT enhances tissue oxygenation and neovascularization and proved clinical efficacy in chronic wounds, post-radiation proctitis and enteritis, perianal fistulizing Crohn’s disease, and acute severe ulcerative colitis. Refractory ulcerative colitis (UC) remains a major therapeutic challenge.

Aims & Methods

We evaluated the tolerability, preliminary efficacy, and mechanistic effects including perfusion kinetics measured with intestinal ultrasound (IUS) of 10 and 20 sessions of HBOT in patients with UC. PARADOX was an investigator-initiated, prospective, open label, uncontrolled, dose-finding pilot trial (phase 2a) in biologic-experienced patients with moderate-to-severe, highly refractory UC with a follow-up of 26 weeks (Mayo score >5, MES ≥2, failed ≥2 classes advanced therapies). Patients (n=16; 8 per arm) continued optimized, stable dose background therapy and received 10 or 20 sessions HBOT (2.4 ATA, 120 minutes per day with two 5-minute air breaks). The primary efficacy outcome was predefined composite clinical and endoscopic response (3-point and 30% decrease in Mayo score, RB = 0 and 1-point decrease in MES) at week (W) 12. Other outcomes included tolerability; clinical, symptomatic, endoscopic, and biochemical response, and transmural response assessed by IUS including contrast-enhanced ultrasound (CEUS) to evaluate bowel wall thickness (BWT), vascularity and perfusion kinetics. Endoscopy and IUS were centrally read and adjudicated.

Results

Baseline characteristics were comparable in both cohorts with median age: 48 vs 64 years; disease duration: 12 vs 9 years; ≥4 prior advanced therapies: 3/8 in both; Mayo score: 10.5 vs 9.
At W12, the predefined composite clinical and endoscopic response rate was met in 2/8 patients with 10 sessions and 4/8 patients with 20 sessions. Clinical, endoscopic, symptomatic, biochemical, and IUS parameters all improved over time in both HBOT cohorts with a trend towards larger improvement after 20 compared to 10 sessions (See Table).
At W12, clinical responders demonstrated a significant increase in peak enhancement on CEUS compared to baseline (12.1 dB, 95% CI: 0.8 to 34.3), while non-responders showed a numerical decrease (–5.4 dB, 95% CI: –20.9 to 4.0). This divergent trajectory was consistent across perfusion parameters related to both wash-in and wash-out (e.g., time to peak, wash-in and wash-out rate, area under the curve), suggesting a treatment-related vascular response. In contrast, early gains in non-responders had waned by W12. This effect was numerically larger after 20 sessions, supporting a potential dose–response effect.
HBOT was well tolerated with no dose-limiting toxicities.

Conclusion

HBOT is a feasible adjunctive therapy in treatment-refractory moderate-severe UC. CEUS showed improved intestinal perfusion in HBOT responders, which offers promising non-invasive tools for response assessment. These findings provide a rationale for a randomized dose-optimized phase 2 trial with potentially longer duration of treatment.