Xiaocen Zhang, MD; Rani Modayil, MD; and Stavros N. Stavropoulos, MD, FASGE
In this chapter we will discuss the technique of submucosal tunneling endoscopic resection (STER) for subepithelial tumors (SETs) of the upper gastrointestinal (GI) tract. The acronym STER was first coined in the English literature in 2012 by Xu et al,1 and similar techniques of varying names were reported almost simultaneously by different groups in 2012. These include submucosal endoscopic tumor resection (later renamed per-oral endoscopic tunnel resection, POET) by Inoue and colleagues2,3 and endoscopic submucosal tunnel dissection (ESTD) by Gong et al.4 A direct derivative of the now widely accepted per-oral endoscopic myotomy (POEM) technique, STER/POET/ESTD (for simplicity we will use the STER acronym henceforth in this chapter) is one of the 2 novel techniques developed over the past 5 years to achieve purely endoscopic Natural Orifice Transluminal Endoscopic Surgery (NOTES) resection of deep-seated SETs involving or arising from the muscularis propria and/or adventitia (the other technique being endoscopic full-thickness resection, EFTR).
Upper Gastrointestinal Subepithelial Tumors and Management
The majority of GI subepithelial tumorous lesions are mesenchymal tumors (GIMTs), with the most recognized and studied member of these being GI stromal tumors (GISTs). GISTs are believed to originate from the interstitial cells of Cajal and feature a KIT or platelet-derived growth factor receptor alpha mutation. All GISTs are considered to have malignant potential and are risk-stratified according to their location, size, and mitotic count. Surgical resection is recommended for any GIST ≥ 2 cm by the National Comprehensive Cancer Network Task Force.5 Insufficient data exist regarding the biological behavior of small GISTs (< 2 cm) discovered incidentally on endoscopy. Small gastric GISTs without high endoscopic ultrasound features may be managed by endoscopic surveillance at 6 to 12 months.5 Non-GIST mesenchymal tumors (the majority of which are leiomyomas in the upper GI tract, followed by neurogenic tumors such as schwannomas, fibrous tumors, and other rare entities) may carry a lower risk of malignant transformation but again because of the rarity of these tumors, data on their natural history are scant.6,7 One of the challenges in managing these tumors is the difficulty in differentiating these tumors from GISTs. Current endoscopic sampling techniques such as endoscopic ultrasound/fine-needle aspiration/fine-needle biopsy fail to achieve histologic diagnosis in up to 30% to 40% of SETs8 and do not yield adequate tissues for accurate mitotic rate assessment. An important predictor of tumor histology is tumor location. Esophagus: leiomyoma>> GIST>> others. Esophagogastric junction: leiomyoma> GIST>> others. Stomach: GIST>>leiomyoma≈Schwannoma≈fibrous tumor≈others. The more distal the tumor is in the upper GI tract, the more likely it is a GIST. When there is suspicion that a tumor may be a GIST, it should be managed as a GIST. When the suspicion for GIST is low, management is mostly symptom based and should take into consideration rate of tumor growth, endoscopic ultrasound features, patient preference, and the risk/benefit of surveillance vs excision (for example, yearly endoscopic surveillance vs endoscopic resection).
Role of Endoscopic Resection in Managing Upper Gastrointestinal Subepithelial Tumors
Since GIMTs (mainly GISTs and leiomyomas) represent the vast majority of upper GI SETs and are often the presumptive diagnosis when making management decisions, they will be the focus of the following discussion. Several features of GIMTs render them good targets for endoscopic resection.
- GIMTs are not locally invasive and follow hematogenous rather than lymphatic pathways when they metastasize. Therefore, a wide resection margin or lymphadenectomy is not required5 and enucleation is adequate from an oncologic standpoint.
- Owing to the malignant potential of these tumors, resection or long-term endoscopic surveillance is recommended for known or suspected GISTs ≥ 2 cm. However, for tumors < 5 cm, these recommendations, driven by the inability to accurately risk-stratify these tumors with current diagnostic techniques, generate a large burden of surgery and endoscopy for tumors that in their majority pose little risk for malignancy. Therefore, a minimally invasive, low-morbidity approach to excision would be ideal for these tumors.
Laparoscopic wedge resection for gastric SETs is safe and effective but it is invasive and its technical feasibility depends on tumor location: the gastric body (greater curvature and anterior wall), fundus (greater curvature, anterior wall, and posterior wall), or proximal antrum (anterior wall) are easier locations to access; conversely, the lesser curvature of the body or antrum, the cardia, or the prepyloric region are challenging locations where a partial or subtotal gastrectomy may be required, particularly for larger tumors.9–11 Video-assisted thoracoscopic (VATS) enucleation of esophageal leiomyomas has been reported to have good results12 but is an infrequently performed procedure and not widely available. When laparoscopic wedge resection or VATS enucleation is not an option, the traditional method would be to perform partial organ resection—either partial gastrectomy or esophagectomy. These are extensive procedures that substantially affect patients’ quality of life. In comparison, flexible endoscopy provides direct access to all upper GI locations and can offer therapeutic tumor resection. However, certain locations can be somewhat challenging even for endoscopic access and require technique modifications and/or advanced operator skills (eg, the proximal esophagus and the deep gastric fundus, for which a special transcardia tunneling technique has been developed; see discussion below). Nevertheless, we should note that the areas of challenging surgical access (esophagus, esophagogastric junction, and prepyloric antrum) are those where endoscopic resection is the easiest. The often intraluminal growth pattern of GIMTs also makes them easier targets for endoscopy compared to laparoscopy/thoracoscopy (Figure 34-1). Endoscopic resection, when technically feasible, offers an excellent resolution to the GIMT management dilemma for tumors ≤ 5 cm: It avoids the cost and anxiety of long-term endoscopic surveillance and, unlike surgery, it achieves complete en bloc extirpation of these tumors via a minimally invasive, organ-sparing approach that preserves natural anatomy and allows faster recovery.
One of the theoretical concerns for endoscopic resection of GIMTs is that a microscopic negative margin (R0 resection) can often not be achieved. While R1 margin for GISTs is traditionally considered an unfavorable prognostic factor,13–15 evidence from a large series and a prospective trial found no difference in recurrence-free survival between those with R1 and R0 resections.16,17 The findings from these series suggesting equivalence between R0 and R1 resection may be particularly applicable to the endoscopic resection of small upper GI GISTs (the target of endoscopic resection techniques). In these small tumors with an endoscopically identifiable well-defined pseudocapsule, removal of the tumors with an intact pseudocapsule would result in an R1 designation if the usual pathologic criteria are applied since no normal tissue outside the tumor is present in the specimen. However (unlike cases in which microscopic tumor is left behind because of compromise or rupture of the tumor pseudocapsule), in these cases complete enucleation has been achieved with no true residual tumor present. As long-term follow-up data after endoscopic resection emerge, the validity of these postulates will hopefully be further strengthened.
Submucosal Tunneling Endoscopic Resection Technique
STER is a direct offshoot of POEM, a submucosal, tunnel-assisted access to the esophageal muscle to effect a full-thickness incision of the muscle for the therapy of achalasia. Therefore, not surprisingly, it was first reported by POEM pioneers.1,2,4 In STER the tunneling concept is utilized to create a safe working space for dissection and removal of tumors mainly arising from or involving the muscularis propria. The tunnel entrance is then closed with endoclips or sutures to restore integrity of the GI wall. The skills and technique of STER are similar to those of POEM. In Figure 34-2 we present the most frequently used dissection implements for STER. A stepwise description of the STER technique is further illustrated in Figures 34-3 through 34-5.
(A) A submucosal tunnel is established approximately 3 to 5 cm proximal to the tumor. The tunnel creation technique is identical to that of POEM. We recommend as short a tunnel as feasible to avoid “missing” small tumors because of a shift in tunnel orientation during dissection and challenges in extracting larger tumors from a long tunnel.
(B) Once the tumor capsule is encountered, the tunnel is extended over and around the tumor to free it from the mucosa.
(C) After completion of the dissection on the mucosal side, deeper dissection on the muscularis propria side is undertaken. Utmost care is taken to maintain integrity of the pseudocapsule. In tumors with interwoven muscle bundles into the pseudocapsule of the tumor, a wider margin should be pursued to ensure pseudocapsule integrity. Obviously for tumors involving or arising from the muscularis propria or even extending beyond the GI wall, a full-thickness resection of the wall is required to achieve complete en bloc removal of the intact tumor. Compared to direct EFTR, STER permits more limited endoscopic maneuvering because of the restricted space inside the tunnel. However, full-thickness resection of the wall including the adventitia and even serosa is less of a concern than in EFTR since secure closure is easily achieved by the tunnel mucosa sealing the full-thickness breech in the GI wall as is the case for the full-thickness myotomy during POEM.18
(D) In STER, the final portion of the resection, which is to free the tumor from its distal attachment, can be challenging. The bulk of the tumor impedes visualization and maneuvering at the distal end, particularly for larger and irregularly shaped tumors. Some operators utilize a snare to cut the last muscularis propria attachment but attention is required to avoid compromising the distal margin. A double-opening technique (DO-STER) has been developed to solve this problem and also allows for easier extraction of the tumor from the tunnel (see discussion that follows).