The submucosal tunneling technique was originally developed to provide safe access to the peritoneal cavity for natural orifice transluminal endoscopic surgery procedures. With this technique, the submucosal tunnel becomes the working space for partial myotomy and tumor resection. The submucosal space has come to represent the “third space” distinguished from gastrointestinal lumen (first space) and peritoneal cavity (second space). New applications continue to be developed and further clinical applications in the future are anticipated. This article summarizes the current applications of submucosal tunneling endoscopic resection for subepithelial tumors and describes other related uses of submucosal tunneling.
Key points
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STER seems to be an effective therapy for treatment of small and medium size gastrointestinal tumors originating from the muscularis propria.
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Common complications of STER are gas-related, most of which resolve with conservative treatment without surgical intervention.
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New applications of submucosal tunneling technique continue to be developed and further clinical applications in the future are anticipated.
Introduction
The submucosal tunneling technique, originally developed at the Mayo Clinic, was described as submucosal endoscopy with a mucosal flap safety valve. It has been shown to be a technically feasible access method for natural orifice transluminal endoscopic surgery (NOTES). The submucosal tunneling technique was subsequently adapted for endoscopic esophageal myotomy for the treatment of achalasia in humans, known as per oral endoscopic myotomy (POEM). During the POEM procedure, the submucosal tunnel becomes the working space for partial esophageal myotomy. Inspired by this technique, Xu and workers used a submucosal tunnel as the working space for endoscopic resections and called the technique submucosal tunneling endoscopic resection (STER). We refer to this as tunneling endoscopic muscularis dissection because it allows precise dissection and resection of tumors as deep as the muscularis propria. This article summarizes the current applications of STER for subepithelial tumors and describes other related uses of submucosal tunneling.
Introduction
The submucosal tunneling technique, originally developed at the Mayo Clinic, was described as submucosal endoscopy with a mucosal flap safety valve. It has been shown to be a technically feasible access method for natural orifice transluminal endoscopic surgery (NOTES). The submucosal tunneling technique was subsequently adapted for endoscopic esophageal myotomy for the treatment of achalasia in humans, known as per oral endoscopic myotomy (POEM). During the POEM procedure, the submucosal tunnel becomes the working space for partial esophageal myotomy. Inspired by this technique, Xu and workers used a submucosal tunnel as the working space for endoscopic resections and called the technique submucosal tunneling endoscopic resection (STER). We refer to this as tunneling endoscopic muscularis dissection because it allows precise dissection and resection of tumors as deep as the muscularis propria. This article summarizes the current applications of STER for subepithelial tumors and describes other related uses of submucosal tunneling.
Submucosal tunneling endoscopic resection
Indications
STER for subepithelial tumors is generally limited to tumors less than 3.5 cm in diameter because subepithelial tumors greater than 3.5 cm are technically difficult to retrieve from the submucosal tunnel and mouth because of the limited size of the esophageal submucosal tunnel. Large tumors may also result in poor endoscopic visualization because of the mass effect. A few cases of resection of subepithelial tumor greater than 3.5 cm have been reported, although some were removed by piecemeal resection and some had a minimum diameter less than 3.5 cm. Tumor size is an important indicator of gastrointestinal stromal tumor (GIST) risk of malignancy, and en bloc resection is preferred because piecemeal resection results in tumor capsule rupture and thus violates an important principle of cancer surgery. Piecemeal resection of benign lesions, such as leiomyomas, is considered acceptable but because the histology of a subepithelial tumor often cannot be accurately diagnosed by endoscopic ultrasound (EUS)-guided aspiration or other endoscopic biopsy techniques before operation and considering the technical difficulties mentioned previously, we recommend the 3.5-cm limit rule be followed.
In terms of location, STER is suitable for tumors originating from the muscularis propria layer of the esophagus or cardia and for many tumors located in the greater curvature of the distal gastric body. However, because it is difficult to create a gastric submucosal tunnel for tumors in the deep fundus or lesser curvature of the gastric body and antrum often the only choice is endoscopic direct full-thickness resection in a retroflexed fashion. For subepithelial tumors arising from muscularis propria in the circular funnel-like cardia area within 8 cm of the gastroesophageal junction, a transcardiac endoscopic tunneling technique is generally a feasible, safe, and easy therapeutic approach from below the cardia. Hu and colleagues also reported that STER was a feasible, safe, and effective method for treating rectal subepithelial tumor originating from the muscularis propria layer.
Preparation and Equipment
Before the procedure, routine EUS and esophageal computed tomography (CT) are performed to determine the size, possible layer of origin, margin, and growth pattern of the subepithelial tumors and to provide information regarding anatomic features of the adjacent structures. In our center, we perform a special esophageal inflatable CT scan in which air is infused into the esophageal lumen through a previously inserted nasoesophageal tube during chest CT scan. Esophageal inflatable CT scan provides superior visualization of the relationship between the subepithelial tumor and the esophageal wall and offers the advantage of a multiazimuthal observation in one plane. Other investigators have also confirmed that CT is especially useful to complement and validate the EUS findings and provides comprehensive and accurate information for confirmation of the use of an endoscopic therapeutic approach. STER procedures are performed under general anesthesia with tracheal intubation. In most cases, a carbon dioxide insufflator is used for carbon dioxide (CO 2 ) gas insufflation during the procedure. CO 2 has advantages compared with room air including fast diffusion and rapid absorption reducing the incidence of clinically important cutaneous emphysema, mediastinal emphysema, and pneumothorax.
Technique/Procedures
The first step is creation of a submucosal tunnel to expose the tumor. After submucosal injection of a solution of epinephrine in saline (1:100,000) and/or indigo carmine, a 2-cm longitudinal mucosal incision is made with a Hook knife, which is our preference, or other similar knife without insulated tip approximately 5 cm proximal to the lesion. For gastric lesions 3 cm is sufficient because of elasticity of gastric wall. A submucosal tunnel is then created between mucosal and muscular layers using endoscopic submucosal dissection technique while advancing toward the tumor. Submucosal tunneling is extended beyond the tumor to secure sufficient working space for tumor resection at the most difficult distal side of the tumor. It is important not to perforate the mucosa during submucosal tunneling because preserving the integrity of the digestive tract mucosa prevents leakage of the gastrointestinal (GI) contents into the body cavity and promotes early wound healing. Repeated injections of saline solution are especially helpful to differentiate the mucosal layer from the tumor mass and to avoid unexpected mucosal injury.
The second step is tunneling endoscopic enucleation of the subepithelial tumor from the muscularis propria. Endoscopic enucleation is performed within the submucosal tunnel by dissecting the tumor away from any connecting muscle fibers. For tumors involving the deep layers of the muscularis propria, circumferential full-thickness muscularis propria resection is performed using the endoscopic knife and even snare resection if necessary. The highest priority during the procedure is safe and complete resection of the tumor, without disruption of the tumor capsule. The tumor is finally removed via the submucosal tunnel. The resection site and tunnel is examined for remnant tumor and bleeding. En bloc resection is defined as the presence of an intact fibrous capsule of resected tumor and the absence of any remnant of tumor observed at endoscopy. Recently, we had success by using a single tunnel to resect multiple esophageal subepithelial tumors originating from the muscularis propria layer ( Fig. 1 ).
Finally, closure of mucosal incision at the tunnel entry site is accomplished with endoclips or other endoscopic closure devices. At the end of the procedure, before withdrawal of the endoscope, careful endoscopic inspection is performed to confirm the integrity of mucosal overlying the tunnel.
Postoperative Care and Follow-Up
All patients are admitted for inpatient hospital observation. Proton pump inhibitors and broad-spectrum antibiotics are prescribed for 3 days. The patients are monitored for chest distress, dyspnea, and blood oxygen saturation. If necessary, temporary chest tube drainage is performed. Commonly, patients are given nothing by mouth on postoperative Day 1. Liquid diet is started on Day 2. An endoscopic examination is done 3 days after the initial procedure to evaluate the condition of the mucosa followed by barium swallow radiography to check for leakage. If both tests are normal, a regular soft diet is initiated. Postoperative pathologic examination includes examination of the lesion margins, cell type, and mitotic count per 50 high-power fields and immunohistochemical staining for CD117, CD34, smooth muscle actin, desmin, and S-100 markers. For incompletely resected GISTs with medium or high risk of malignancy, secondary surgery or imatinib treatment is recommended. Follow-up includes clinic visits to assess for delayed complications, repeat standard endoscopy, and EUS 2 months after procedures and then annually. For moderate-and high-risk GISTs, cross-sectional imaging is also performed at 6- to 12-month intervals for 3 to 5 years and then annually as is recommended after surgical resection of such tumors.
Outcomes
Although most subepithelial tumors are benign, some have malignant potential, especially GISTs originating from the muscularis propria. Resection of these tumors provides a definitive diagnosis and may be curative. Several studies have evaluated the use of the submucosal tunneling technique to resect subepithelial tumors ( Table 1 ). The en bloc resection rate was 83.3% to 100%. In the initial case series, two of nine (22%) patients required conversion to open surgery. Both of these patients had tumors that were too large (60 mm and 75 mm, respectively) for safe endoscopic removal because of a loss of endoscopic overview. All subepithelial tumors had detailed histopathologic diagnosis including those with piecemeal resection. To date, no postresection recurrences have been reported. However, long-term follow-up studies regarding outcome are needed to better evaluate the long-term success of the procedure. The largest retrospective study enrolled 290 patients with subepithelial tumors originating from the muscularis propria of the upper GI tract and was reported at the US Digestive Disease Week in 2014. The available data are consistent with the notion that STER is an effective and a safe method for upper-GI submucosal tumors with diameter size less than 35 mm. The overall rates of en bloc resection and piecemeal resection were 95.4% and 4.6%, respectively, and local recurrences and distant metastasis have not been reported in follow-up. Tumor size and shape significantly affect the en bloc rate with large size and irregular shape being associated with more difficult procedures, an increased risk of requiring piecemeal resection, and were significant contributors to STER-related complications.
| Ref | No. Cases (Tumors) | Location | Mean Tumor Size (mm) | Pathology | Mean Operating Time (min) | En Bloc Resection Rate, n (%) | Complications | Follow-Up Time (mo) and Recurrence |
|---|---|---|---|---|---|---|---|---|
| Xu et al | 15 (15) | 9 esophagus, 3 cardia, 2 body, 1 autrum | 19 | 5 GISTs, 9 leiomyomas, 1 glomus tumor | 78.7 | 15 (100) | 1 Pp, 1 Pt, 1 SE | 3.9 None |
| Inoue et al | 7 (7) | 3 esophagus, 4 cardia | 18.6 | 1 GISTs, 5 leiomyomas, 1 aberrant pancreas | 152.4 | 7 (100) | None | 5.5 None |
| Gong et al, 2012 | 12 (12) | 8 esophagus, 4 cardia | 19.5 | 7 GISTs, 5 leiomyomas | 48.3 | 10 (83.3) | 2 Pt and SE | — |
| Liu et al | 12 (12) | 7 esophagus, 5 cardia | 18.5 | 2 GISTs, 9 leiomyomas, 1 schwannoma | 78.3 | 12 (100) | 8 ME and SE, 4 Pt, 3 Pp, 2 PE | 7.1 None |
| Wang et al | 80 (83) | 67 esophagus, 16 cardia | 23.2 | 15 GISTs, 68 leiomyomas | 61.2 | 81 (97.6) | 2 SE, 1 Pt, 1 MP, 3 chest pain | 10.2 None |
| Ye et al, 2014 | 85 (85) | 60 esophagus, 16 cardia, 9 stomach | 19.2 | 19 GISTs, 65 leiomyomas, 1 calcifying fibrous tumor | 57.2 | 85 (100) | 6 Pt, 8 SE, 4 Pp | 8 None |
| Lu et al | 18 (19) | 19 fundus | 20.1 | 13 GISTs, 6 leiomyomas | 75.1 | 19 (100) | 2 Pp | 5 None |
| Li et al, 2015 | 32 (32) | 3 fundus close to cardia, 12 corpus close to cardia, 6 lesser curvature of corpus, 11 greater curvature of antrum | 23 | 11 GISTs, 18 leiomyomas, 1 calcifying fibrous tumor, 1 glomus tumor, 1 schwannoma | 51.8 | 32 (100) | 1 bleeding, 6 Pp, 3 Pt and SE | 28 None |
| Wang et al | 57 (57) | 57 esophagogastric junction | 21.5 | 7 GISTs, 46 leiomyomas, 2 schwannoma, 1 lipoma, 1 granular cell tumor | 47 | 57 (100) | 12 ME and SE, 5 Pt, 3 Pp, 2 PE | 12 None |
| Zhou et al, 2015 | 21 (21) | 21 esophagogastric junction | 23 | 6 GISTs, 15 leiomyomas | 62.9 | 21 (100) | 9 ME and SE | 12 None |
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