Introduction

There has been an ongoing debate over the appropriate timing of direct endoscopic necrosectomy (DEN) following the initial endoscopic ultrasound (EUS)-guided transmural drainage of walled-off necrosis (WON). We aimed to examine the superiority of immediate DEN over the drainage-oriented step-up approach in terms of the time to WON resolution.

Aims & Methods

This multicentre, open-label, superiority, randomised trial (WONDER-01) was implemented including patients who were scheduled to receive EUS-guided treatment of WON at 23 centres in Japan (1). Eligible patients were randomly assigned at a 1:1 ratio to receive either immediate DEN or the step-up approach. In both arms, a lumen-apposing metal stent was used as the first-choice stent for EUS-guided drainage. In the immediate DEN arm, DEN was initiated during (or within 72 hours of) the initial EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand DEN was considered after clinical observation for 72-96 hours. The primary endpoint was time from the randomization to clinical success, which was defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e., body temperature, white blood cell count, and C-reactive protein). The secondary endpoints included technical success, procedure-related adverse events, and mortality. All efficacy and safety endpoints were analysed on an intention-to-treat basis. This study was registered with ClinicalTrials.gov (registration number, NCT05451901), and the recruitment and follow-up for the primary endpoint have been completed.

Results

Between July 2022 and December 2023, a total of 70 patients were enrolled (33 and 37 patients in the immediate DEN and step-up arms, respectively) with baseline characteristics being well-balanced between the arms. In an analysis of the primary endpoint, the immediate DEN was associated with a shorter time to clinical success compared to the step-up approach (P < 0.001) with median times of 31 days (95% confidence interval, 19-34 days) and 44 days (95% confidence interval, 38-52 days), respectively. As per the protocol, all patients in the immediate DEN arm received DEN compared to 46% in the step-up approach arm (P < 0.001), but the rates of procedure-related adverse events were compatible between the arms (24% vs. 22%, respectively; P = 0.79). No differences were noted between the immediate DEN and step-up approach arms in terms of the rates of technical success (100% vs. 98%, respectively; P = 0.26) and mortality (12% vs. 5.4%, respectively; P = 0.31).

Conclusion

In patients with symptomatic WON, immediate DEN following EUS-guided transmural drainage shortened the time to clinical success compared to the drainage-oriented step-up approach without increase in adverse outcomes. Immediate DEN can be a first-line treatment option for this patient population.

References

(1) Sato T, Saito T, Takenaka M, Iwashita T, Shiomi H, Fujisawa T, et al. WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis-study protocol for a multicentre randomised controlled trial. Trials. 2023;24(1):352.

Disclosure

H.I. declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. Y.N. declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. The other authors declare no conflicts of interest related to this article.

Introduction

​Transanal Minimally Invasive Surgery (TAMIS) and Endoscopic Submucosal Dissection (ESD) are minimally invasive techniques for en bloc resection of large non-pedunculated rectal lesions. While TAMIS has been widely adopted in the Netherlands, ESD uptake has been slower. No randomized trials have compared these methods, leaving the choice of technique dependent on local expertise rather than evidence.

Aims & Methods

This multicenter-randomized non-inferiority trial (NTR7281) aimed at comparing TAMIS and ESD regarding effectiveness, safety, patient burden, and costs. In total, 198 patients with non-pedunculated rectal lesions >2 cm, located ≤15 cm from the anal verge, were included. Patients were randomized in a 1:1 ratio to TAMIS or ESD, with stratification by polyp size (20–40 mm or >40 mm) and distance from the dentate line (<10 mm, 10–99 mm, 100–150 mm), after an expert panel had judged the lesions suitable for inclusion. Exclusion criteria included deep submucosal invasion on endoscopy or imaging (with endoscopy prioritized in case of discordant findings), prior endoscopic resection attempt, and an unfavorable risk-benefit ratio for local treatment (e.g., poor general condition or very short life expectancy). The primary endpoint was cumulative local recurrence at 12 months (non-inferiority margin: 6%). Secondary endpoints included radical (R0) resection rate, complications (AGREE classification), patient burden (COREFO, EQ-5D-5L, QLQ-CR29), and cost-effectiveness. Intention-to-treat analysis was performed.

Results

Of the 198 randomized patients (98 TAMIS, 100 ESD), 5 crossed over from TAMIS to ESD and 1 from ESD to TAMIS. One patient dropped out before treatment as result of non-related metastatic disease. Mean polyp size was 42.0 mm. Mean procedure time was 108.7 minutes for ESD and 78.1 minutes for TAMIS. In total, 156 benign and 41 malignant lesions (39 T1, 2 T2, and 1 T3) were resected. At 12 months, 6 recurrences occurred: 0 (0%) in the ESD group and 6 (6.4%) in the TAMIS group, all benign, with a 6.4% difference favoring ESD (95% CI: -11.8 to -1.5), confirming non-inferiority and also superiority. R0 resection rates were 83% for ESD and 71% for TAMIS (p = 0.047). Overall complication rates were similar (p = 0.33). Colorectal functional outcomes at 12 months were similar and comparable to baseline. Quality-adjusted life years were also similar (0.90 for ESD and 0.91 for TAMIS, p = 0.356). Despite a significant difference in the average initial procedure cost (€2.628 for ESD and €3365 for TAMIS, p < 0.001), the average total cost over 12 months was similar (€7.134 for ESD and €7216 for TAMIS, p = 0.934).

Conclusion

This trial is the first to show that ESD is non-inferior to TAMIS for local recurrence at 12 months in en bloc resection of large non-pedunculated rectal lesions. ESD showed superior radical resection rates and lower initial procedural costs, while both techniques had similar safety profiles, colorectal functional outcomes, quality-adjusted life years, and total 12-month costs.

Disclosure

The TRIASSIC study received funding by ZonMw and Applied medical.
A. Koch received consultancy fees from Microtech, Erbe and Fujifilm