Duodenal neuroendocrine tumors: how safe is endoscopic resection?

Neuroendocrine tumors (NETs) are heterogenous neoplasms that can occur anywhere in the gastrointestinal (GI) tract; within the GI tract, NETs are most commonly encountered in the small bowel (jejunum/ileum), rectum, and pancreas, with duodenal neuroendocrine tumors (dNETs) accounting for only 2.8% of incident NETs (1). Nevertheless, in recent decades, NET incidence has been rising, attributed to increasing use of diagnostic imaging and endoscopy, with a 4-fold rise dNET incidence reported between the 1980s and 2010 (2). In the majority of cases, dNETs are sporadic and non-functional (i.e., no clinical hormonal syndrome is associated), raising the question of appropriate intervention for frequently incidental diagnoses of small, generally indolent, neoplasms (3).

European Neuroendocrine Tumor Society (ENETS, 2023) guidelines recommend endoscopic resection for non-functional dNETs <10 mm in size after appropriate evaluation (including endoscopic ultrasound for tumors 5–10 mm), as risk of nodal metastasis is low, and similar survival outcomes as compared to surgery (4). The optimal method of endoscopic resection, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), is not known.

With greater ability to achieve en bloc and pathologic margin-negative (R0) resection compared to EMR, ESD has become more broadly adopted and is the first line therapy in epithelial lesions, such as early gastric cancer. The added depth of dissection allows treatment of submucosal lesions, which may not be feasible with EMR. The duodenum remains the most technically difficult location to perform ESD, with high adverse event rates reported for epithelial lesions (intraprocedural perforation 13–50%, delayed perforation 9%, bleeding 18%, need for surgery 14%) (5-7). Outcomes specific to submucosal lesions in the duodenum are not well studied.

In this issue of the Journal of Gastrointestinal Oncology, Li et al. present the outcomes of patients undergoing endoscopic resection for non-ampullary dNETs ≤10 mm (8), adding valuable clinical data, particularly for ESD (10 of 12 patients), for which few studies exist (9-13). Technical outcomes of ESD, including en-bloc and pathologic complete resection were favorable at 90% and 80%, respectively (2/10 patients with a positive vertical margin on pathology), and comparable to one larger study of 20 patients (11). The only adverse event reported was one case (10%) of intraprocedural perforation, though the patient did not require surgery. This patient also had a positive vertical margin, doubly illustrating the challenges of ESD in the thin duodenal wall. The authors report 53 months of follow up time after endoscopic resection (ER), during which no remnant lesions, recurrence, or distant metastasis were found (including in four higher-risk patients with piecemeal resection, grade 2 lesions and positive pathologic margins).

While this study by Li et al. does not have sufficient sample size for comparison of EMR vs. ESD techniques, literature for EMR in dNETs allow for more robust comparison. In one large study by Noh et al. (including dNET <10 mm, N=86), EMR achieved en bloc resection in 98.8%, with relatively low adverse event rates (5.8% perforation, 2.3% post-procedure bleeding) (14). As may be expected for use of EMR in submucosal lesions, the rate of histologic complete resection was low, with only 55.8% achieving histologic complete resection (the majority, 36.4%, had a positive vertical margin). Despite high rates of margin positivity, only 6% patients experienced a recurrence during a median follow up of 88 months. Only younger age at diagnosis and lesion size (≥10 mm) were identified as risk factors for NET recurrence on multivariable analysis.

Alternative options to endoscopic resection for patients with dNETs are limited given the significant morbidity of surgery (local resection or pancreatoduodenectomy), and limited evidence for a watch-and-wait strategy (15). While larger, ideally prospective studies and longer-term follow up are desired, this study by Li et al. adds to the growing body of literature supporting the safety and efficacy of endoscopic resection and ESD for dNETs, at least in specialized centers with highly-skilled endoscopists. However, in the context of existing technologies, EMR is more readily available, has shorter procedure times and lower adverse event rates compared to ESD. Endoscopists may reasonably question the utility of the technically-challenging ESD in small and indolent dNETs, risking high adverse event rates to achieve a technically superior, but clinically equivalent outcome. The utility of ESD may become more evident in specific scenarios, such as in patients with larger dNETs who are not candidates for conventional surgery, and/or younger patients with longer life expectancy, to which further research should be directed.

Acknowledgments

Funding: J.Y.Y. receives research and salary support through NIH T32 (CA225617).

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-471/coif). J.Y.Y. receives research and salary support through NIH T32 (CA225617). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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