Endoscopic resection of laterally spreading lesions of the ampulla: more answers and more questions

Endoscopic resection has become the first-line approach for ampullary neoplasms with limited intraductal extension and in the absence of invasive cancer. Nonetheless, endoscopic resection of ampullary lesions should be recognized as a technically demanding procedure, with a high risk of serious site-specific adverse events and the potential for recurrence. Lateral extension of the ampullary adenoma makes the procedure even more complex and there are limited data on the endoscopic approach of these lesions.

In this issue of Endoscopy, Klein et al. present their retrospective analysis on outcomes after endoscopic resection of large laterally spreading lesions of the papilla (LSL-P) and adenomas confined to the ampulla [1]. The authors defined an LSL-P as an ampullary lesion with a ≥ 10 mm extension beyond the ampullary mound; lesions confined to the mound or with < 10 mm extension were considered conventional ampullary adenomas. All lesions underwent comprehensive pre-resection evaluation with endoscopy, cross-sectional imaging, and/or endoscopic ultrasound to assess for endoscopic resectability and exclusion of invasive disease. Endoscopic retrograde cholangiopancreatography with evaluation of both the distal biliary and pancreatic duct systems was routinely performed prior to endoscopic resection. For LSL-Ps, an inject and resect endoscopic mucosal resection (EMR) technique was used to remove the laterally spreading component prior to resecting the ampullary portion in one piece. Pancreatic duct stenting was attempted in all patients, and the indication and choice of biliary stent was at the discretion of the endoscopist. All patients were scheduled to receive proton pump inhibitor therapy twice daily for 6 weeks after the procedure. Criteria for admission were not standardized but were based on patient’s comorbidities, intraprocedural events (i. e. bleeding), post-procedural symptoms, and endoscopists’ judgment. First surveillance was performed at 4 – 6 months followed by intervals based on the presence of recurrence on histopathology.

“Although this study suggests that laterally spreading lesions of the ampulla can be treated endoscopically similarly to conventional ampullary adenomas, several issues remain unanswered, including the rate of rare adverse events and the risk of recurrence.”

In all, 125 lesions (44 LSL-Ps and 81 ampullary adenomas) with a median size of 20 mm were resected endoscopically. Complete endoscopic resection was achieved in 122 cases (97.6 %), with no differences between LSL-Ps and conventional adenomas, even though LSL-Ps were larger (median 35 vs. 15 mm; P < 0.001) and contained more advanced pathology (38.6 % vs. 18.5 %; P = 0.01). When compared with conventional adenomas, LSL-Ps were associated with a higher rate of intraprocedural bleeding (50.0 % vs. 24.7 %; P = 0.003) and a trend towards increased delayed bleeding (25.0 % vs. 12.3 %; P = 0.08). Lesion size and number of resected specimens were the only independent predictors for intraprocedural and delayed bleeding, respectively. Post-procedural pancreatitis occurred in 7.2 % of cases, with no difference between the two groups. One perforation was reported in a conventional adenoma with multiple prior incomplete attempts at endoscopic resections. Recurrence/residual disease was histologically confirmed in 18 of 106 cases (17.0 %) on initial surveillance endoscopy, with both piecemeal resection (P = 0.02) and number of resected specimens (P = 0.02) identified as independent predictors of recurrence. In patients with at least two follow-up endoscopies available (n = 68), 95.6 % remained free of residual/recurrent disease at a median of 29 months. Based on these findings, the authors concluded that LSL-Ps can be resected endoscopically with comparable outcomes to standard ampullectomy, albeit with a higher risk of bleeding.

The authors should be commended for putting forth this cohort study on endoscopic resection of ampullary neoplasms, and specifically, for distinguishing and comparing outcomes between LSL-Ps and lesions confined to the ampulla. The high eradication rates reported are comparable to previous studies [2] [3] [4], and further suggest that even LSL-Ps can be adequately managed endoscopically. However, endoscopic resection in the duodenum, particularly when involving the papilla, poses some unique challenges, which deserve consideration when interpreting the results from this study. It should be highlighted that these data originate from a highly specialized center in endoscopic resection and may not be generalized. Even in this setting, when compared with adenomas confined to the ampulla, resection of LSL-Ps were associated with a higher rate of intraprocedural bleeding. Although the study was underpowered to show a statistically significant difference in delayed bleeding, it should be emphasized that the risk nearly doubled for resection of LSL-Ps compared with conventional ampullary adenomas (25.0 % vs. 12.3 %). Similarly, the small sample size in each group limited inferences on other important performance parameters, including rate of perforation, post-procedural pancreatitis, and papillary stenosis. Finally, recurrence has been a common concern with endoscopic ampullectomy, particularly if there is intraductal extension. Such recurrence may be harder to detect and compare with large-area EMR performed elsewhere in the gastrointestinal tract. In this study, the authors showed that histologically confirmed recurrence/residual adenoma was reported in 17.0 % of cases and was associated with piecemeal resection. Importantly, the rate of recurrence and long-term efficacy of endoscopic therapy remains to be better defined considering that, in this study, half of the patients had only a single surveillance endoscopy at 4 – 6 months after the procedure, or no follow-up at all.

In summary, Klein et al. demonstrate that the endoscopic resection rates of LSL-Ps and conventional adenomas are comparable, when performed in a specialized center. It is our opinion that endoscopic ampullectomy is a technically complex procedure that should be performed exclusively by endoscopists who are skilled in endoscopic resection techniques and proficient in advanced pancreaticobiliary endoscopy. As shown in this study, bleeding occurs with a predictably high frequency, especially with larger lesions and increasing number of resected specimens. Hence, there is a need to develop a predetermined protocol such as routine post-procedure admission for observation, which we have implemented at our institution. Although this study suggests that LSL-Ps can be treated endoscopically similarly to conventional ampullary adenomas, several issues remain unanswered including, but not limited to, the rate of rare adverse events and the risk of recurrence. Conducting randomized controlled trials may be challenging because of the prohibitively high number of patients that would be necessary, but additional large prospective studies are needed to further corroborate these initial findings.

• References

• 1 Klein A, Qi Z, Bahin FF. et al. Outcomes after endoscopic resection of large laterally spreading lesions of the papilla and conventional papillary adenomas are equivalent. Endoscopy 2018; 50: 972-983
• 2 Irani S, Arai A, Ayub K. et al. Papillectomy for ampullary neoplasm: results of a single referral center over a 10-year period. Gastrointest Endosc 2009; 70: 923-932
• 3 Ridtitid W, Tan D, Schmidt SE. et al. Endoscopic papillectomy: risk factors for incomplete resection and recurrence during long-term follow-up. Gastrointest Endosc 2014; 79: 289-296
• 4 Kang SH, Kim KH, Kim TN. et al. Therapeutic outcomes of endoscopic papillectomy for ampullary neoplasms: retrospective analysis of a multicenter study. Gastrointest Endosc 2017; 85: 746-755