Endoscopic resection of sporadic duodenal neuroendocrine tumors: Why is this not so easy?

Although duodenal neuroendocrine tumors (NETs) comprise only 2 % – 3 % of all NETs, their incidence appears to be rising, possibly as a result of the increasing use of upper gastrointestinal (GI) endoscopy [1] [2] [3]. The majority of these lesions are small and probably unrelated to the patient’s symptoms, but once discovered, they pose a dilemma: removal of duodenal NETs is desirable because of the risk of developing lymph node or liver metastases, but performing endoscopic resection in the duodenum is by no means straightforward. This is a challenging portion of the GI tract for endoscopists, with high risks owing to the thin and richly vascular duodenal wall and access that is often difficult. This is reflected in the considerable complication rates associated with endoscopic resection of any lesions in the duodenum [4].

Duodenal NETs in particular pose a challenge, as the majority lie within the submucosa. Techniques described for endoscopic removal include strip biopsy in early studies, conventional endoscopic mucosal resection (EMR), cap and snare EMR, EMR with a ligation device, endoscopic submucosal dissection (ESD), or a hybrid EMR – ESD approach [5] [6] [7]. Several small case series have shown that these techniques appear to be effective in the treatment of small duodenal NETs but there is an appreciable complication rate, mainly related to procedural or delayed bleeding [8]. Prior to endoscopic resection, staging investigations, including endoscopic ultrasound, should be used to confirm that the NET is confined to the submucosal layer and that there is no evidence of regional lymph node or distant metastases.

The European Neuroendocrine Tumor Society (ENETS) guidelines recommend endoscopic removal for nonampullary duodenal NETs < 10 mm in size, and surgical resection for ampullary/periampullary NETs of all sizes or duodenal NETs > 20 mm in diameter [1] [2]. For nonampullary NETs in the 10 – 20 mm size bracket, either endoscopic or surgical resection is recommended on a case-by-case basis [1] [2].

In this issue of Endoscopy, Gincul et al. present the results of a retrospective case series of the outcomes of endoscopic resection of 32 duodenal NETs in 29 patients from two centers over a period of two decades [9]. Lesions < 20 mm in size were included and all lesions were resected by conventional EMR or cap-assisted EMR. The complication rate in this series was high at 38 % overall, including bleeding in nine cases and perforation in two cases. One patient died following a severe procedure-related hemorrhage. The complication rate was not associated with the technique used (conventional EMR vs. cap-assisted EMR). The relationship between size of lesion and complication rate was not examined. R0 excision was achieved in 56 % of cases, and three patients with an R1 excision went on to undergo surgery following endoscopic resection; the remaining patients either declined surgery or were unfit for surgery. Two patients developed lymph node or distant metastases during follow-up. Interestingly, none of the R1 patients developed local recurrence during the follow-up period.

The R1 resection rate reported by Gincul et al. is similar to that found in other series, and is perhaps influenced by endoscopists being wary of potential complications in the duodenum and therefore adopting a more cautious approach [7] [9]. ESD results in a lower R1 resection rate, but this advantage must be balanced against the potentially higher complication rate [4]. Similarly, surgery will achieve a high R0 resection rate but at the cost of potentially greater morbidity and mortality [10].

The authors were unable to identify any risk factors for R1 resection but this may be due to the small number of lesions in each category (size/location). The submucosal origin of these tumors explains the high R1 resection rate, which is mainly related to the deep margin. R1 resection rates can be reduced by penetrating more deeply with techniques such as ESD, but unlike mucosal neoplasia the exact relationship between NET size, histology, and the risk of lymph node metastasis is not well established. The problem therefore is selecting which patients should undergo radical resection and which should not. It is therefore important that further data are collected and, given the infrequent occurrence of these tumors, an international registry will be required. Despite evidence of a rising incidence, duodenal NETs are a relatively rare lesion when it comes to endoscopic resection, hence the dearth of evidence and experience in this field. All cases should be staged and discussed at a multidisciplinary meeting prior to any planned therapy.

The outcomes reported by Gincul et al. confirm that endoscopic resection of duodenal NETs carries considerable risks and that obtaining a complete pathological resection is difficult. Therefore, these procedures should only be undertaken by endoscopists with extensive experience in endoscopic resection techniques in high-volume centers. Prophylactic clipping has been shown to be very effective in reducing the delayed bleed rate after colonic EMR and may be of value in this setting to reduce the risk of both delayed bleed and perforation [11]. A full-thickness resection device has been successfully used in the resection of duodenal neoplasia, and could prove to be a very effective and safe tool for small duodenal NETs. Further evidence is needed to confirm the efficacy of such a device but, conceptually, it seems to be an ideal resection tool for these tumors that originate deep within the submucosa [12]. Advances in endoscopic techniques and skills can potentially reduce the R1 rates and complication rates in the future, but further understanding of the natural history of these lesions is also needed.

Although uncertainty remains about the optimal management of duodenal NETs, the results reported by Gincul et al. broadly support the current ENETS guidelines, recommending endoscopic resection for lesions < 10 mm, surgery for those > 20 mm, and careful consideration between the two techniques for those of 10 – 20 mm. This should take into account imaging, local expertise, and, of course, the fitness and views of the patient. We should not forget the fact that many of these patients are elderly and have co-morbidities, and that NETs can be very slow to progress, so doing nothing can be a wise option in some high-risk patients.

As the authors note, further data are needed to evaluate the long-term results, and a large international database collating the outcomes of endoscopic resection of duodenal NETs would go some way to achieving this.

• References

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