Abbreviations:
ESD (endoscopic submucosal dissection), ACE resection study (Australian Colonic Endoscopic resection study)Endoscopic mucosal resection (EMR) has become the primary resection method for large colorectal polyps ≥20 mm in size.
1
An increasing number of studies have been published to support the efficacy and safety of this method and its superiority over surgical resection.2
, 3
However, 2 main issues remain a challenge. First, EMR is associated with a delayed bleeding risk of between 2% and 10%.4
, 5
Second, the frequency of recurrence is 10% to 15%.3
Although recurrent polyps can be managed endoscopically in the majority of patients, this fairly high rate justifies early, and potentially more frequent, follow-up procedures.6
The factors responsible for local recurrence are not completely understood, but incomplete resection can be assumed to be the source of regrowth. Some evidence suggests that resection margins often harbor nonvisible residual neoplasia.
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A major risk factor for recurrence is piecemeal resection.8
In addition, intraprocedural bleeding, which may obscure visualization and affect the quality of resection, has also been linked with increased recurrence.4
To reduce potential remaining polyp tissue, ablative methods have been applied. In a small study of 21 patients, argon plasma coagulation of the resection perimeter substantially reduced recurrence.9
However, this study was criticized for its small size and unexpectedly high incomplete resection rate in the control group (64%). Alternatively, endoscopic submucosal dissection (ESD) may facilitate more en bloc resections and possibly lower recurrence rates, but it is limited by greater procedural risk, increased procedural time, and a higher demand for technical skill.10
The bottom line is that the efficacy and safety of these techniques is still debated, and other methods to improve EMR are of interest.11
, 12
In this issue of Gastrointestinal Endoscopy, the study by Bahin et al
13
explores the idea of reducing the rate of recurrence by extending the EMR to include a large healthy margin beyond the visible extent of the lesion.13
This observational study used prospectively acquired data on the resection of ≥20-mm nonpedunculated polyps as part of the Australian Colonic Endoscopic Resection (ACE) study. During the early years of the study (2008-2011), EMR was performed to include a 1-mm to 2-mm healthy margin. Starting in 2012, EMR was extended to include a healthy margin of at least 5 mm. The primary outcome was the rate of residual or recurrent adenoma in biopsy specimens from the resection site at first follow-up colonoscopy, which was performed in all patients after 4 months. The authors compared residual or recurrent adenoma among patients who underwent extended EMR with historic control patients who underwent standard EMR.The patients in both groups had similar characteristics. The mean polyp size was also similar and just under 4 cm in each group. EMR was attempted for 458 lesions in the standard EMR group and for 426 lesions in the extended EMR group, with visibly complete removal in 92% and 93% of patients, respectively. As the main result, the authors found that a larger healthy margin did not lower the rate of residual or recurrent adenoma at follow-up colonoscopy, which was 12% in the standard EMR group and 10% in the extended EMR group (P = .15). The authors also reported that residual or recurrent adenoma was located mostly at the edge of the EMR site in both groups (standard EMR 74%, extended EMR 68%; P = .58). In multiple logistic regression analysis, lesion size, the use of adjuvant thermal ablation, and intraprocedural bleeding were independently associated with residual or recurrent adenoma, whereas extended EMR was not.
This study has several strengths. First, the concept of extending the resection to include a large healthy margin seems to make sense if one expects that residual tissue would be located at the margins. Second, the large number of enrolled patients with a follow-up rate of 80% to 90% is exemplary. Third, the routine acquisition of biopsy specimens from the resection site provided an objective measure of the rate of recurrence. Fourth, the authors excluded patients during 2 periods (beginning of the ACE study and after changing to extended EMR), when the adoption of a new technique may have influenced the results.
Yet, the main result of this study is surprising to both the authors and probably many readers. If we think that local recurrence originates from residual neoplasia, and we know that residual neoplasia often remains at the resection margin, why then would taking a large healthy margin not improve recurrence rates? Are there possible alternative explanations for the observed lack of benefit? Some considerations might include the following.
First, the authors compared taking a large healthy margin (>5 mm) with taking a small healthy margin (1-2 mm). In that sense, the results show only that taking a larger rim does not improve the completeness of resection; when we view it that way, the results are not a surprise. Second, the use of historic control patients may have introduced unmeasured or confounding factors that threaten the validity of the results. Third, several important baseline characteristics differed between the 2 groups that could have biased the results. The extended EMR group showed a trend toward including more lesions with a previous unsuccessful attempt at removal (16% vs 12%), lesions that were removed piecemeal (89% vs 83%), and a much higher rate of intraprocedural bleeding (20% vs 7.5%). These factors have been associated with either technical difficulties or an increased risk of incomplete resection or recurrence.
6
, 8
, 14
By contrast, there were more sessile serrated adenomas/polyps in the extended EMR group, which may actually favor less recurrence.15
A separate matter is that adjuvant thermal ablation was less-frequently used in the extended EMR group (14% vs 21%), which could mean either that fewer lesions appeared to require ablation or that they were at higher risk for recurrence because ablation was not used. Technical skill also undoubtedly advanced since the inception of the study. Because the total EMR time was similar between groups, the effective EMR time for each lesion in the extended EMR group must have been shorter. This may indicate that the lesions were easier to resect, or it may reflect improved technical skill. Taken together, several factors might have affected the outcome in the extended EMR group in either direction and therefore leave a small doubt about the generalizability of the findings.What do we learn from the study? Obtaining a healthy margin may not completely remove all polyp tissue or prevent recurrence. It seems that the problem of recurrence is more than just at the perimeter of a large polypectomy. Although a complete en bloc resection by continuous submucosal dissection would capture the entire central field, piecemeal EMR is liable to leave some imperceptible neoplastic cells at the margin with each passing of the snare. In other words, part of the problem may be at the margin of each resected piece, rather than just at the margin of the lesion as a whole.
Taken together, the results provide a strong argument that there is no benefit in extending the EMR to include a larger healthy margin around the lesion—if anything, it increases the risk of intraprocedural bleeding. It should be emphasized that at least a small healthy margin was obtained in the control group, which is a practice that should be continued and might explain the overall low recurrence rate.
3
Additional efforts to ensure completeness of resection should focus on minimizing the risk of microscopic residual neoplastic tissue. The preliminary results from a prospective randomized trial involving 768 lesions where soft tissue coagulation with the snare tip was applied to the EMR margin showed a reduction in the rate of recurrence from 20% to 6%.16
Further work toward reducing recurrence rates will also need to focus on how the intervening sections during EMR are handled, just as much as the perimeter. The key to improving completeness of resection may depend on minimizing piecemeal resection and on minimizing the risk of microscopic residual neoplasia, particularly at the margins of each resected piece.- Klein A.
- Jayasekeran V.
- Hourigan L.
- et al.
A multi-center randomized control trial of thermal ablation of the margin of the post endoscopic mucosal resection (EMR) mucosal defect in the prevention of adenoma recurrence following EMR: preliminary results from the “SCAR” study.
Gastroenterology. 2016; 150: S1266-S1267
Disclosure
Dr Pohl is a consultant for Interscope, Inc. All other authors disclosed no financial relationships relevant to this publication.
References
- Outcome of EMR as an alternative to surgery in patients with complex colon polyps.Gastrointest Endosc. 2016; 84: 315-325
- Endoscopic resection is cost-effective compared with laparoscopic resection in the management of complex colon polyps: an economic analysis.Gastrointest Endosc. 2016; 83: 1248-1257
- Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.Gut. 2016; 65: 806-820
- Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.Clin Gastroenterol Hepatol. 2014; 12: 651-661.e1-3
- 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
- Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the australian colonic EMR (ACE) study.Gut. 2015; 64: 57-65
- Incomplete polyp resection during colonoscopy: results of the complete adenoma resection (CARE) study.Gastroenterology. 2013; 144: 74-80.e1
- Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis.Endoscopy. 2014; 46: 388-402
- Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations.Gastrointest Endosc. 2002; 55: 371-375
- Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal tumors: a meta-analysis.World J Gastroenterol. 2014; 20: 8282-8287
- Colorectal endoscopic submucosal dissection: when and by whom?.Endoscopy. 2014; 46: 677-679
- Argon plasma coagulation after piecemeal polypectomy of sessile colorectal adenomas: long-term follow-up study.Endoscopy. 2003; 35: 212-218
- Extended endoscopic mucosal resection does not reduce recurrence compared with standard endoscopic mucosal resection of large laterally spreading colorectal lesions.Gastrointest Endosc. 2016; 84: 997-1006
- Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia.Gastroenterology. 2011; 140: 1909-1918
Pellise M, Burgess NG, Tutticci N, et al. Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions. Gut. Epub 2016 Jan 19.
- A multi-center randomized control trial of thermal ablation of the margin of the post endoscopic mucosal resection (EMR) mucosal defect in the prevention of adenoma recurrence following EMR: preliminary results from the “SCAR” study.Gastroenterology. 2016; 150: S1266-S1267
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- Extended endoscopic mucosal resection does not reduce recurrence compared with standard endoscopic mucosal resection of large laterally spreading colorectal lesionsGastrointestinal EndoscopyVol. 84Issue 6
- PreviewEffective interventions to prevent residual and/or recurrent adenoma (RRA) after EMR of large sessile and laterally spreading colorectal lesions (LSL) are yet to be determined. RRA may occur due to inconspicuous adenoma at the EMR margin. We aimed to determine the efficacy and safety of extended EMR (X-EMR) compared with standard EMR (S-EMR).
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