Is Underwater Endoscopic Mucosal Resection Better Than Conventional EMR for Large Colon Polyps?

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Summary of study (Nagl S, et al. Gastroenterology 2021;161:1460–1474)

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Summary of study (Nagl S, et al. Gastroenterology 2021;161:1460–1474)

Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. In a prospective, randomized study the Augsburg Group investigated whether underwater endoscopic mucosal resection (UEMR) was superior to CEMR for large (20– 40mm) sessile or flat colorectal polyps.  During a 3-year period the authors recruited 148 patients with sessile or flat colorectal polyps between 20 and 40 mm in size and were randomly assigned to UEMR or CEMR on a 1:1 basis. 

Six endoscopists with at least 200 CEMR experience performed the procedures. They obtained en bloc resection rates in 33.3% in the UEMR group and 18.4% in the CEMR group (P = 0.045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = 0.025). 

Overall recurrence rate was 15.1% in the UEMR group and 24.6% in the CEMR group (P 1⁄4 .253). The recurrence rates for lesions of >30 mm to 40 mm in size were 6.3% and 42.9% for UEMR and CEMR, respectively (P 1⁄4 .031).

The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P < .001). Adverse events did not differ between both groups (P 1⁄4 .611). 

The authors concluded that UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to 40 mm in size. 

Comments: The authors are to be commended for performing a randomized, prospective study.

However, the results do not appear as promising, nor applicable as they look.

Let’s analyze why?

Although the study was designed to be 1:1 randomization, there were four out of six endosocopists that did not perform any (n=0) UEMR. Also, how come there are 81 polyps in UEMR and 76 in the CEMR group?

Standard CEMR is usually done with diluted epinephrine and/or using indigo carmine dye. Also, other injection solutions besides normal saline are available. It is not common to perform CEMR using saline alone. This provided a disadvantage to the CEMR group. Furthermore, during traditional CEMR using injection as a hemostatic technique is accepted. In this study hemostasis was only allowed with a “coagulation forceps”.

Concerningly, five patients undergoing UEMR had to be crossed-over to the CEMR group, as the patients bled and the procedure using UEMR had to be aborted.

The authors aimed at “en-bloc” resection in all patients. This is controversial and dangerous for lesions larger than 30 mm, unless one is using ESD or hybrid EMR-ESD methods. Furhermore, the largest snare was 25 mm in diameter. Therefore, it is difficult to understand how the authors were able to perform a en-bloc resection of lesions larger than the snare.

During UEMR saline was used to fill the colon. In general, water is done to perform water immersion colonoscopy and UEMR.

There appears to be biased picture selection, without any photos on conventional EMR. The UEMR photos show one successful case. Photos showing a piecemal UEMR or failed UEMR would add objective value to this endoscopic study. Indeed, the majority of UEMR and CEMR cases were considered "failures" as less than a third could be removed in toto (or R0).

The study size may be severly underpowered, as the authors considered a recurrence rate of 30% for CEMR and only 10% for UEMR. Their results are in contradiction with the a priori sample calculations, with very high recurrence rates.

The authors based their conclusion on a per-protocol analysis. However, we know that intention-to-treat analysis should be used preferentially to present results.

Do these patients reflect routine clinical practice? Likely not. This appears to be a highly selected group of healthy patients. It took three years to find 178 polyps. Very low use of antithrombotics, 21% and 22%, respectively. If there were 5 patients needing cross-over from UEMR to CEMR in this highly selected group of healthy patients with low percentage of use of antithrombotics, one would expect more bleedings and complications in the real practice, where lots of our patients are ASA3 (excluded in this study).

Also concerning were the huge interoperator variability of polyp resections, with 3 operators resecting less than 7 lesions, one resecting 11, and the remaining to 23 and 24, respectively. Incongruently, only 2 of six endosopists performed UEMR (54 and 27 respectively).

The median hospital stay was 2, ranging from 1-26. It is not usual for healthy patients, ASA 1 or ASA 2, as recruited in this study to remain in hospital for more than a day after CEMR or UEMR.

Finally, although the authors aimed at performing en bloc and/or R0 resection of all lesions, the results for both methods were quite dismal. En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group; R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively.

In sum, this study shows on the difficulties of performing randomized studies using different endoscopic resection techniques.

The poor en bloc or R0 resection rates do not support the use of UEMR nor CEMR using just normal saline as a lifting agent. 

UEMR appears to be an interesting option to resect colon polyps, but given the high success rates of en bloc and R0 resection using CEMR or EMR-ESD or ESD, these results are not strong enough to change my current practice.

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