Endoscopic submucosal dissection for duodenal tumors

Introduction

Endoscopic submucosal dissection (ESD) is widely adopted as an effective treatment strategy for esophageal, gastric, and colonic neoplasms. Recently, the therapeutic indication has been expanded to the duodenal neoplasms in many institutions, but it causes a lot of controversy because of unknown clinicopathological characteristics of the tumors and high incidence rate of complications associated with endoscopic procedures.

Clinicopathological characteristics of duodenal tumors

The prevalence of duodenal epithelial neoplasms is reported to be 0.03% to 0.4% of the patients undergoing the upper endoscopy (1,2), which is smaller than those of other digestive neoplasms. Majority of them are diagnosed as adenomas or mucosal adenocarcinomas located at descending part of the duodenum (3-6). The malignant transformation rate of adenomas differs depending on the previous reports. Some suggested the duodenal adenomas progressed to adenocarcinomas in 30% to 80% of the cases (7,8), but Okada reported that only 4.7% of 47 duodenal adenomas progressed to the adenocarcinoma during follow-up and pointed out a high risk of progression to adenocarcinoma for high grade adenomas of 20 mm or more in size (9). The incidence rate of lymph node metastasis of duodenal adenocarcinomas is also unclear because of the lack of cases treated by surgical resection. Some previous case-series reports showed the mucosal cancers were free from lymph node metastasis, suggesting the endoscopic therapeutic indication for them (10,11).

Merits and faults of ESD and EMR

There are basically two ways of endoscopic resection of duodenal tumors, ESD and endoscopic mucosal resection (EMR). The advantage of ESD to EMR is higher en bloc resection rate and lower local recurrence rate regardless of the tumor size, location, and submucosal fibrosis, which has been much proven in the endoscopic treatment for esophageal, gastric, and colonic tumors (12). However, those advantages may be small for the endoscopic treatment for duodenal tumors compared with that for other digestive tumors (Tables 1,2). EMR seems inferior to ESD in en bloc resection and local recurrence without restriction of duodenal tumor size. However, several reports suggested a similarly good prognosis of the cases after piecemeal resection as those after en bloc resection (13-16), and the incidence of complication was apparently more frequent in ESD than in EMR, especially for the duodenal perforation (Tables 1,2). Intraoperative perforation and delayed perforation after ESD were reported to be 6.3–50% and 0–14.3%, respectively (3-6). Recently, Ono et al. analyzed reported the clinical short-term outcomes of 1397 patients, who were endoscopicaly treated for duodenal neoplasms, by using questionnaire data taken from thirteen advanced institutions in Japan (4). In this large number of analysis, intraoperative perforation and delayed perforation each occurred in 12.1% (54/445) and 4.0% (18/445) of the cases of ESD and 1.6% (13/798) and 0.6% (5/798) of the cases of EMR, showing a higher incidence of perforation in the cases of ESD. Additionally, emergency surgery was performed in 5.4% (24/445) of the cases of ESD and 0.4% (3/798) of the cases of EMR, and it was more frequently required in the cases of delayed perforation (52.2%: 12/23) than in the cases of intraoperative perforation (19.4%: 13/67). These results of advanced institutions in Japan show the difficulty to decrease the incidence of duodenal perforation associated with ESD only by the technical improvement.

Table 1 Previous reports regarding the outcomes of duodenal ESD
Full table

Table 2 Previous reports regarding the outcomes of duodenal EMR
Full table

The clinical characteristics of the perforation are different between ESD and EMR. ESD-associated perforation usually occurs as a small linear hole at early stage and tears easily to be gradually enlarged along with the endoscopic procedures. Additionally, the endoscopic resection becomes technically more difficult to continue (Figure 1). On the other hand, EMR-associated perforation occurs as a small roundish hole by an incidental whole layer resection on snaring. However, the lesion has already been resected, and it is usually relatively easy to close the small perforation by using clipping devices.

Figure 1 A case of early duodenal cancer located at the descending part of the duodenum (A). Perforation was complicated on submucosal dissection as a small hole of the proper muscle layer, and the endoscopic suture was attempted by using clipping device (B). However, the perforated site was gradually torn to become a large hole during the endoscopic procedure and a failed clip was dropped into the retroperitoneum (C). After removing a failed clip, the perforation was completely closed, but ESD had become difficult to continue, resulting in the piecemeal resection by snaring (D). Administration of the carbapenem antibiotic was started during the procedure, and the patient was treated conservatively to be discharged a week after ESD.

Some specific anatomical features of the duodenum can be given as the reason why the duodenal ESD frequently complicates a perforation. First, the narrow, crooked, and deeply located lumen makes it difficult to keep an adequate visual field for ESD. Second, the submucosal injection is difficult due to abundant Brunner’s glands and fibrosis in the submucosal layer, leading to the intraoperative severe conditions for submucosal dissection. Lastly, the duodenal muscle layer is very thin compared with other digestive tract (Figure 2), which is probably the biggest cause of perforation by minor physical or chemical damage including burning effect, compression of endoscopic devices, and tissue damage by bile and pancreatic juice.

Figure 2 The whole layer-resected specimen by duodenal EMR complicating a perforation (A). This histopathologic picture shows abundant Brunner’s gland at submucosal layer and a very thin proper muscle layer as 300–500 µm (B). This histopathologic picture makes it easy to understand the reason for high incidence rate of perforation associated with duodenal ESD.

Countermeasure for the duodenal perforations by ESD and EMR

Some countermeasures for the duodenal perforation have been suggested; carbon dioxide (CO₂) supply, prophylactic clipping, polyglycolic acid (PGA) sheets shielding, and the laparoscopic and endoscopic cooperative surgery (LECS). Using CO₂ for the air supply during ESD is necessary for the possible intraoperative perforation, regardless of the kind of digestive tract (12). The following two measures aim not for the prevention of an intraoperative perforation but for that of a delayed perforation. Prophylactic mucosal closure by clipping device after ESD is effective for the protection of the exposed muscle layer (Figure 3). However, the achievement depends on the size and location of the resected bed and scope instability (16,17). PGA sheet, an absorbable mesh used to seal tissue defects with fibrin glue, was reported to be effective for the prevention of delayed bleeding after gastric ESD (18) and postoperative stenosis after esophageal extensive ESD (19). Recently, this shielding method has been reported to be also effective for the prevention of delayed perforation after duodenal ESD (20). LECS has been developed as a minimally invasive surgery for the gastrointestinal stromal tumor (21), and also proposed as an alternative method of ESD for the case of early stage digestive cancers which is difficult to treat by ESD. Some case series reports have suggested the efficacy of LECS for the treatment of duodenal tumors; the partial duodenal resection or seromuscular suturing of resection bed after ESD by using LECS technique (22,23). However, the extensive resection by LECS is considered to cause the postoperative stenosis, and is inadaptable to the lesions near the duodenal papilla.

Figure 3 A case of early duodenal cancer located at the superior duodenal angle (A). The lesion was resected by ESD, and the postoperative mucosal defect reached half of the circumference (B). To prevent a delayed perforation, the resected bed was sutured from the end of it by using a clipping device (C). The resected bed has been completely sutured (D).

Current status and future prospects of duodenal ESD

Thus, duodenal ESD has not yet reached the recommendable measure for the endoscopic treatment of duodenal tumors. To overwhelm the various problems concerning the duodenal ESD, the endoscopic skill-up is necessary but insufficient, because a high incidence of complications has been experienced in the advanced Japanese institutions. Nevertheless, to reduce the incidence of complications as much as possible, the cases of possible indication of duodenal ESD should be collected to such specific institutions with advanced techniques and experiences. Additionally, the lesions likely to be resectable by EMR should not be treated by ESD, and we should have the prudence in aggressively performing duodenal ESD.

The complication of duodenal ESD we should overcome the most is an intraoperative perforation, which is most frequently experienced but has a lack of effective preventive measures. It seems difficult to prevent the intraoperative perforation singly by the progress of ESD techniques or related devices, implying the necessity of a fundamental change of the therapeutic method. From the perspective of a combined treatment, the further radical progress of LECS may possibly change the treatment for the duodenal tumors to more safe and feasible one.

Conclusions

The duodenal ESD still have many unsolved problems regarding feasibility and safety even by introducing various ideas, and the indication should be well discussed in consideration of the expected therapeutic effect and complications.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

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