Is it really necessary to achieve R0 resection in duodenal superficial lesions? If yes, does it justify surgery?

Superficial duodenal lesions include several types of tumor, namely nonampullary duodenal adenomas, which range in size from a few millimeters to several centimeters and rarely have extensive circumferential extension into the papilla, adenocarcinomas, and subepithelial lesions (SELs; mainly neuroendocrine tumors and stromal tumors). Multiple other lesions are described in the duodenum but they do not require follow-up or resection (Brunner’s hyperplasia, gastric heterotopy, lipoma, or submucosal cysts). The first step in management is therefore to make a precise endoscopic differential diagnosis, possibly assisted by echo endoscopy with a diagnostic fine-needle biopsy in cases of SELs.

The most frequently occurring lesions that require resection are the superficial nonampullary duodenal tumors (SNADT), for which several technical options are currently in use: cold snare for the smaller ones (< 6 mm) and en bloc or piecemeal endoscopic mucosal resection (EMR) for the nonmalignant adenomas, with endoscopic submucosal dissection (ESD) reserved for suspected superficial submucosal invasion and nonlifting nonmalignant lesions caused by de novo submucosal fibrosis or secondary to previous biopsy or incomplete resection. Recent large series of EMR showed a complete resection rate of over 90 % [1]. In a systematic review and meta-analysis that included 440 patients with 485 duodenal nonampullary adenomas from 14 retrospective studies, the mean polyp size ranged from 13 mm to 35 mm and complete endoscopic resection by polypectomy or EMR was achieved in 93 % of the lesions [2].

“Duodenal laparoscopic and endoscopic cooperative surgery may deserve more attention in the Western world for very specific indications, such as subepithelial lesions exceeding the limits of endoscopic full-thickness resection, and superficial nonampullary duodenal tumors with noninvasive but malignant features.”

In contrast, for SELs, experience with endoscopic resection in the duodenum is more limited, as it usually involves endoscopic full-thickness resection (FTR). New, recently developed devices such as duodenal over-the-scope clips allow safer resection of these lesions, but endoscopic treatment remains limited to lesions distant from the major and minor papillae, and less than 15 mm in diameter [3]. These devices have also been used in recurrent SNADTs or poor lifting lesions (< 25 mm) with success [3].

In this issue of Endoscopy, Nunobe et al. report excellent results obtained with laparoscopic and endoscopic cooperative surgery (LECS) that combines laparoscopic surgery with endoscopic treatment for duodenal neoplasms [4]. The technique, which was first introduced for treatment of gastric SELs, was applied to duodenal tumors (D-LECS) to avoid perforation during and after ESD. Two variants were used in the study: ESD or endoscopic FTR combined with laparoscopy for closure of the defect or laparoscopic FTR under guidance of endoscopy to assess tumor margination. The authors (on behalf of the Japanese Society for the Study of LECS) analyzed outcomes of 206 patients with median preoperative tumor size of 13.5 mm (range 3–40), including 66 patients with lesions ≥ 20 mm, 103 adenomas (50 %), 53 adenocarcinomas (26 %), 38 neuroendocrine tumors (18 %), and 12 gastrointestinal stromal tumors and others (6 %). Median operating time was 180 minutes (range 65–606), intraoperative complications occurred in 7.3 %, conversion to open surgery was necessary in 5.3 %, postoperative complications occurred in 11.2 %, reoperation was required in 1.0 %, and median postoperative hospital stay was 9 days (range 4–76). The en bloc resection rate was 96 % and the R0 resection rate was 95 %, with no recurrence observed over a median follow-up period of 28.6 months (range 0.2–130). The authors concluded that D-LECS for duodenal neoplasms reduced the risk of postoperative perforation with oncological safety and feasibility. Postoperative complications after D-LECS increased with longer operative time.

The data shown by the authors may indeed justify the use of D-LECS rather than open and laparoscopic surgery. Literature on duodenal surgery for SNADT is limited, mostly comparing transduodenal excision and segmental duodenal resection vs. pancreaticoduodenectomy or pancreas-sparing duodenectomy, with lower morbidity rates. However, transduodenal excision is associated with a 5-year recurrence rate of 32 %, justifying regular postoperative endoscopic surveillance with feasible further rescue endoscopic resection of recurrences [5]. Concerning pancreas-preserving duodenectomy, a cohort study demonstrated significantly lower recurrence rates with surgery vs. EMR (0 % vs 32 %; P  < 0.001), but with a trend toward higher adverse event rates in the surgical group (26 % vs. 15 %). D-LECS has the advantage of lower morbidity compared with surgery alone owing to the more targeted approach and the fact that D-LECS with ESD can be completed in a closed manner, thereby preventing tumor dissemination and infection from spillage of duodenal contents.

There are only a few studies comparing endoscopic and surgical outcomes, most of them showing lower mortality and morbidity, shorter procedure time, and shorter hospital stay in endoscopically treated patients [6]. But the aim of the Nonube et al. study was to demonstrate superiority in terms of safety when compared with duodenal ESD, with its known high incidence of adverse events (up to 30 %), even in experienced centers [7]. In Europe, duodenal ESD is not very popular, but in Japan and Asia, large SNADTs (mostly > 20 mm) are often considered for ESD, which allows en bloc and R0 resections. Although comparative data analysis between EMR and ESD showed better R0 rates (> 90 %) for large lesions with ESD, no differences in long-term outcomes and survival could be demonstrated, and most importantly, significantly higher rates of complications were observed with ESD [8].

So, does complete resection of adenomas needs an en bloc R0 resection? Despite the excellent results from the Nunobe et al. study, the focus of endoscopic resection for SNADTs should still primarily be safety rather than en bloc or R0 resection. The superior safety profile of EMR is the major factor favoring EMR as a first-line technique, despite the higher recurrence rate that may require further endoscopic therapy. Most SNADTs do not exceed 20–30 mm in size so that mucosal defect closure can be easily performed with various endoscopic techniques and devices reducing the bleeding and perforation rates, and recurrence rates can be decreased by optimizing resection and ablation of margins, with recurrences limited to the very large lesions, often involving the ampullas. D-LECS may however deserve more attention in the Western world for very specific indications, such as SELs exceeding the limits of over-the-scope clip-based FTR and SNADTs with noninvasive but malignant features.

Publication History

Article published online:
29 July 2021

• References

• 1 Probst A, Freund S, Neuhaus L. et al. Complication risk despite preventive endoscopic measures in patients undergoing endoscopic mucosal resection of large duodenal adenomas. Endoscopy 2020; 52: 847-855
• 2 Navaneethan U, Hasan MK, Lourdusamy V. et al. Efficacy and safety of endoscopic mucosal resection of non-ampullary duodenal polyps: a systematic review. Endosc Int Open 2016; 4: E699-708
• 3 Bauder M, Schmidt A, Caca K. Endoscopic full-thickness resection of duodenal lesions – a retrospective analysis of 20 FTRD cases. United Eur Gastroenterol J 2018; 6: 1015-1021
• 4 Nunobe S, Ri M, Yamazaki K. et al. Safety and feasibility of laparoscopic and endoscopic cooperative surgery for duodenal neoplasm: a retrospective multicenter study. Endoscopy 2021; 53: 1065-1068
• 5 Bartel MJ, Puri R, Brahmbhatt B. et al. Endoscopic and surgical management of nonampullary duodenal neoplasms. Surg Endosc 2018; 32: 2859-2869
• 6 Xu M, Wu J, Yu L. et al. Surgical versus endoscopic resection of large sessile duodenal and papillary lesions. Eur J Gastroenterol Hepatol 2020; 32: 48-53
• 7 Pérez-Cuadrado-Robles E, Quénéhervé L, Margos W. et al. Comparative analysis of ESD versus EMR in a large European series of non-ampullary superficial duodenal tumors. Endosc Int Open 2018; 6: E1008-E1014
• 8 Pérez-Cuadrado-Robles E, Quénéhervé L, Margos W. et al. ESD versus EMR in non-ampullary superficial duodenal tumors: a systematic review and meta-analysis. Endosc Int Open 2018; 6: E998-E1007