Prophylactic clips at polypectomy? Yes.

Prevention of colorectal cancer through the endoscopic resection of pre-cancerous polyps is an important benefit of colonoscopy but is associated with a risk of serious adverse events, including bleeding. While immediate bleeding is usually managed at the time of the procedure, delayed post-polypectomy bleeding (after discharge from endoscopy unit, up to four weeks later) is considered the most common adverse event after polyp resection and, as all endoscopists know, can be significant in some cases. The prophylactic placement of endoscopic clips to close the mucosal defect has the potential to decrease this risk.

The benefit of clipping is directly related to the baseline risk of bleeding. Although a landmark retrospective study in 2013 showed a significant reduction in delayed post-polypectomy bleeding with clips,1 several subsequent studies had less impressive results, and meta-analyses suggested no benefit from the placement of clips. What these studies have in common is a low risk of bleeding in the control group (not clipped), and the most likely reason is the inclusion of small and medium size polyps. Even if clipping low-risk polyps was beneficial, the absolute risk reduction would be very small, which means a large number-needed-to-treat, and a prohibitive cost.  We have learned in recent years that the risk factors for delayed post-polypectomy bleeding for non-pedunculated polyps (flat and sessile) include large size of the lesion (≥ 2 cm, and much higher risk if ≥ 4 cm), location (right side of the colon) and treatment with anti-thrombotic agents. Other important patient-related risk factors for post-polypectomy bleeding include advanced age and presence of significant co-morbidities. A 2015 trial from China showed a benefit from clipping after resection of polyps 1-4 cm,2 but that study included polyps resected by endoscopic submucosal dissection (ESD) as well as endoscopic mucosal resection (EMR), and the results might not be applicable to our daily practice.

Three very recent randomized controlled trials, evaluating the placement of prophylactic clips after polypectomy, are worth discussing in detail. Feagins et al included 1,098 patients with polyps greater than or equal to 1 cm and found no difference in post-polypectomy bleeding (2.9%  vs. 2.3% ) with placement of endoscopic clips.3 The vast majority of polyps were in the 1 cm to 2 cm range, and the subgroup of high-risk lesions (≥ 2 cm, proximal location, resected by endoscopic mucosal resection (EMR) was very small. On the other hand, Pohl et al randomized 919 patients with large (≥ 2 cm) non-pedunculated polyps, resected by EMR, and found a significant reduction in the risk of post-polypectomy bleeding with prophylactic clipping (7.1% vs. 3.5%).4 Most of the benefit was seen for polyps on the right side, and clipping was beneficial independent of polyp size (2 cm to 4 cm vs. > 4 cm) or anti-thrombotic use. Albeniz et al randomized 235 patients with non-pedunculated polyps resected by EMR. All polyps were ≥ 2cm and were considered high-risk for delayed bleeding (GSEED-RE score ≥ 6).5 This study found an elevated baseline rate of bleeding and a strong trend towards reduced post-polypectomy bleeding with clips (12.1% vs. 5%, p=0.053). It is important to note that in the last two trials, distal lesions (distal to the hepatic flexure) were at lower risk for bleeding and did not benefit from prophylactic clipping. And even in the hands of experts, not all lesions were amenable to complete closure with clips (due to size, location and access), and about 15% of post-polypectomy defects could not be clipped at all.

Should we apply endoscopic clips to prevent post-polypectomy bleeding?  The answer is yes, for selected polyps!

So how do I apply all this information in my daily practice? If I find a 3-cm sessile polyp in the cecum of a 76-year-old patient with a history of cardiovascular disease, and after resecting it using EMR techniques, I will spend a few minutes prophylactically closing the defect with clips, given the increased risk of post-polypectomy bleeding (polyp size, location, co-morbidities and age). The goal is to achieve complete closure of the defect, with less than 1 cm in between the clips. On the other hand, if I find an identical polyp, in the descending colon of a 55-year-old healthy patient, I will resect it by EMR, but as the bleeding risk is much lower, I would not apply clips to close this defect, as the additional time, effort and cost are not justified.

It is worth mentioning that studies are currently evaluating if endoscopic mucosal resection without cautery (“cold EMR”) is as effective as traditional “hot” EMR. The limited data available at this time suggests that cold EMR carries a much lower risk of delayed post-polypectomy bleeding, and if this is the technique used for polyp resection, prophylactic clipping is not indicated. Of course, there are other scenarios for which clips are appropriately used during colonoscopy, such as in the treatment of intra-procedural bleeding, as well as in the management of evident or suspected polypectomy-induced perforations (the “target sign”).

So, let’s go ahead, as a community of GI endoscopists, and let’s prevent colorectal cancer by endoscopically resecting all benign-appearing polyps, including the larger ones, especially in those who would not tolerate surgery too well. And if at increased risk for delayed bleeding (large size [≥ 2 cm], right side location, advanced age, co-morbidities or anti-thrombotic therapy), let’s spend a few minutes on the prophylactic placement of endoscopic clips as this will reduce this risk and add a level of safety to our intervention.

Disclosures: Dr. Antaki has reported receiving past research support from Merck and Boston Scientific. The views expressed in this article are those of the author and do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

Dr. Keswani says that outside of a narrow subgroup, we cannot confidently say that endoscopic clips are effective.

References

1. Liaquat H., Rohn E., Rex D.K. Prophylactic clip closure reduced the risk of delayed postpolypectomy hemorrhage: experience in 277 clipped large sessile or flat colorectal lesions and 247 control lesions. Gastrointest Endosc. 2013;77:401-407.
2. Zhang Q.S., Han B., Xu J.H., et al. Clip closure of defect after endoscopic resection in patients with larger colorectal tumors decreased the adverse events. Gastrointest Endosc. 2015;82:904-909.
3. Feagins L.A., Smith A.D., Kim D., et al. Efficacy of prophylactic hemoclips in prevention of delayed post-polypectomy bleeding in patients with large colonic polyps. Gastroenterology. 2019;doi:10.1053/j.gstro.2019.05.003
4. Pohl H., Grimm I.S., Moyer M.T., et al. Clip closure prevents bleeding after endoscopic resection of large colon polyps in a randomized trial. Gastroenterology. 2019 ;doi :10.1053/j.gastro.2019.03.019
5.Albeniz E., Alvarez M.A., Espinos J.C., et al. Clip closure after resection of large colorectal lesions with substantial risk of bleeding. Gastroenterology. 2019;doi:10.1053/j.gastro.2019.07.037

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