Among 167 SNADETs over a period of 5 years, we recorded a 22.2% rate of clinically significant AE, and found a lesion size ≥ 30 mm to be the only statistically significant risk factor for AE. Noticeably, the risk of AE was not associated with patients’ or other lesions’ characteristics, and currently recommended technique prophylactic measures, such as the closure of the resection bed with clips, had no influence on the risk of AE. The use of a monofilament snare allows, due to an increased rigidity, to better grasp a flat lesion. However, the cutting phase is quicker, possibly resulting in less coagulation of the resection bed, and in a higher secondary bleeding rate explaining the trend although the difference was not statistically significant.
Retrospective studies suggested that delayed bleeding occurred in 4.4–17.4% of cases after EMR of duodenal adenomatous lesions10,11,12,13,14,15,16,17, and that the risk increased with the size of the lesion and the presence of a protruding (Paris type 0–Is) lesion. In the only currently published prospective study including 110 lesions and 118 patients, delayed bleeding occurred in 18.6% of cases18. Although this high rate can be the result of the inclusion of 18% ampullary adenomas, and 30% giant adenomas, it also underlines the possible underestimation of the complications rates after duodenal EMR in most retrospective studies. Aschmoneit-Messer et al., in a prospective study including 50 patients and 61 lesions, showed that prophylactic argon plasma coagulation (APC) of the resection bed lowered the risk of delayed bleeding after EMR of duodenal adenomatous lesions > 20 mm and/or in case of visible vessels ≥ 1 mm19. However, considering a delayed perforation in one out of the six patients managed with APC, the safety of this attidude is debatable. Lepilliez et al., in a retrospective study including 36 patients and 37 lesions, found that no delayed bleeding occurred in patients treated by prophylactic clipping or prophylactic argon plasma coagulation, or in patients treated for intraprocedural bleeding. In the meantime, delayed bleeding occurred in 21.7% of the rest of the patients16. Nonaka et al., in a retrospective study including 113 patients and 121 lesions, showed that delayed bleeding rate dropped from 32 to 7% in cases of prophylactic clipping (p < 0.004)17. These two works, along with others, have contributed to demonstrate that complete closure by clips, feasible in most of the cases for lesions of less than 20 mm, is effective in preventing adverse events20. However, in the large lesions included in our study, complete closure was only feasible in 38.9% of the lesions. Therefore, we cannot exclude that a complete closure of these large lesions would have resulted in a reduced adverse event rate. Therefore, ESGE guidelines recommend prophylactic treatment of delayed bleeding by placing clips to close the mucosal defect or by non-contact hemostatic measures5. Considering the questionable stability and efficacy of hemostatic powders and gels, the most promising options for AE prevention after duodenal endoscopic resection rely in a change of the resection technique, using cold EMR, associated with a lower rate of AE; and improved mucosal defect closure, using endoscopic suturing techniques when complete closure by clips is impossible.
While the 17.7% delayed bleeding rate was in keeping with the literature data, we did not observe any statistically significant benefit of clipping the resection bed. This is likely to be explained by the large size of the resected lesions, with over 45% of lesions > 30 mm, precluding a complete closure of the resection bed with clips.
Immediate perforation, defined by a breach in the muscularis propria during endoscopic resection, occurs in 2.2–6% of the resections10,11,12,13,14,15,16,17. The management of immediate perforations consists in the closure of the perforation with clips, preferably after completing the resection. Perforation typically occurs in pretreated or multibiopsied lesions with submucosal fibrosis, or insufficient submucosal injection. In our cohort, immediate perforation occurred in 2.4% of the resections.
Delayed perforations of the duodenal wall are likely caused by multiples parameters such as thermic aggression from the resection and hemostasis, but also chemical aggression by bile acids and pancreatic fluid. After EMR for duodenal adenomatous lesions, the reported rates range from 1.7 to 7.4%, and account for the 1% mortality associated with this procedure10,11,12,13,14,15,16,17. Our findings were in line with these numbers, with no mortality, and also illustrate the feasibility of endoscopic management of delayed perforations.
Based on retrospective studies, local recurrence rate ranges from 9 to 37%10,13,14,15. It appears to be maximal for piecemeal resections of lesions > 20 mm in size. We found an overall 42.5% recurrence rate and identified high-grade dysplasia, piecemeal resection and multiple resected lesions as potential risk factors. As recurrence was a secondary endpoint we did not perform a multivariable analysis. These high numbers can be explained by the high proportion of piecemeal resection due to the large size of the lesions resected in our cohort.
The strengths of our study were the large number of resections, performed in consecutive and prospectively recorded patients at a single center, including large and giant lesions, with available follow-up data, allowing to assess the recurrence rates. Main limitations are the heterogeneity of the resection tools, reflecting the number of operators involved, the retrospective analysis of the database, leading to loss of data, and the inclusion of patients from an expert center, leading to a selection bias. In addition, multivariable analysis was performed only for the main outcome and not for the secondary endpoints. As the information regarding the location relative to the papilla was most often missing, we could not analyze this parameter.
Underwater EMR (U-EMR) performed in the duodenum is a promising treatment option. Filling the duodenal lumen with water prevents the excessive stretching of the duodenal wall and allows to resect duodenal neoplasms without submucosal lifting. These two factors allowed to reach 87.5–100% complete endoscopic resection with a delayed bleeding rate reaching 25%, and low perforation rate21,22,23,24,25. Endoscopic submucosal dissection allows en-bloc resection rates of 75–100%, with 9–36% of perforations. In addition, duodenal ESD does not result in a lower rate of local recurrences26. As shown in multiples studies, cold snare polypectomy appears to be a safe resection technic for duodenal lesions up to 10 mm27,28. Given these figures, ESGE recommends cold snare polypectomy for lesions up to 6 mm and to limit the use of duodenal endoscopic submucosal dissection to selected cases in expert centers12,14,16,29,30.
Future measures are still at an experimental stage in 2022. Endoscopic suturing of duodenal EMR sites has been described as feasible in a case series of 7 patients31. Considering the size, cost, and maneuverability of the available endoscopic suturing devices, endoscopic suturing of EMR sites is not cost-effective. Upper gastrointestinal full thickness resection device has been performed in 8 patients with duodenal lesions32 with an excellent safety profile, but technical feasibility and histologically complete resection rates in lesions > 20 mm is uncertain.
In conclusion, EMR for supracentimetric duodenal adenomatous lesions is associated with AE such as delayed bleeding or delayed perforation in 22.2% of the cases, particularly in lesions ≥ 30 mm. Preventive measures, such as the complete closure of the mucosal defect with clips is often technically impossible in large lesions, while prophylactic coagulation of the resection bed might increase the risk of delayed perforation.