REVIEW URRENT C OPINION
Submucosal endoscopy: the new frontier of therapeutic endoscopy Mouen A. Khashab, Ahmed A. Messallam, Mohamad El Zein, and Vivek Kumbhari
Purpose of review Peroral endoscopic myotomy (POEM) and submucosal tunneling and endoscopic resection (STER) have been recently described as minimally invasive therapies for achalasia and gastrointestinal subepithelial tumors originating from the muscularis propria, respectively. This review illustrates the latest developments in the field of submucosal endoscopy, focuses on POEM and sheds light on STER. Recent findings Multiple studies from the United States, Asia and Europe have shown that POEM is an effective and safe procedure for achalasia when performed by experienced operators with adequate clinical response in 80–90% of patients. Nonetheless, POEM requires a demanding skill set that involves both advanced endoscopic skills and knowledge of surgical anatomy. In addition, the endoscopist must have the capability to manage procedural complications. Similarly, STER appears to be an effective therapy for treatment of small and medium sized gastrointestinal tumors originating from the muscularis propria. Summary POEM and STER offer minimally invasive and effective treatment alternatives for patients with achalasia, spastic esophageal disorders and upper gastrointestinal tumors originating from the muscularis propria. Keywords achalasia, botox, myotomy, peroral endoscopic myotomy, pneumatic dilation
INTRODUCTION Recent advances in natural orifice translumenal endoscopic surgery (NOTES) [1] and the improvement of devices for endoscopic submucosal dissection (ESD) have culminated in submucosal endolumenal approaches to treat achalasia using peroral endoscopic myotomy (POEM) technique. Submucosal tunneling was initially described by Sumiyama et al. [2], whereas POEM was first described by Pasricha et al. [3] in 2007 in a swine model. Inoue championed translating this innovative procedure into clinical care [4]. Inoue and other investigators have also used the submucosal space to access tumors that arise from the muscularis propria for either sampling or resection of these tumors [submucosal tunneling and endoscopic resection (STER)] [5]. This review illustrates the latest developments in the field of submucosal endoscopy, focuses on POEM and sheds light on STER.
PERORAL ENDOSCOPIC MYOTOMY Traditional endoscopic therapies of achalasia include botulinum toxin injection and pneumatic www.co-gastroenterology.com
dilation, whereas laparoscopic Heller myotomy (LHM) remains the conventional surgical therapy. The use of botulinum toxin has fallen out of favor because of limited durability and potential for increasing risk of subsequent myotomy. A large portion of patients who undergo pneumatic dilation will relapse, mainly during the first year after treatment [6]. Perforation is the most important and serious complication of pneumatic dilation with an overall rate between 2 and 4%. As with pneumatic dilation, the efficacy of LHM decreases with longer follow-up periods. An antireflux operation is typically recommended with LHM because of high risk of postoperative reflux. This is associated with increased postoperative dysphagia [6]. Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Correspondence to Mouen A. Khashab, MD, Assistant Professor of Medicine, Director of Therapeutic Endoscopy, Johns Hopkins Hospital, 1800 Orleans St, Suite 7125 B, Baltimore, MD 21205, USA. Tel: +1 443 287 1960; e-mail: [email protected] Curr Opin Gastroenterol 2014, 30:444–452 DOI:10.1097/MOG.0000000000000102 Volume 30 Number 5 September 2014
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KEY POINTS POEM and STER have been recently described as minimally invasive therapies for achalasia and gastrointestinal subepithelial tumors originating from the muscularis propria, respectively. Multiple studies from the United States, Asia and Europe have shown that POEM is an effective and safe procedure for achalasia with adequate clinical response in 80–90% of patients. STER appears to be an effective therapy for treatment of small and medium sized gastrointestinal tumors originating from the muscularis propria.
POEM is the latest breakthrough as a minimally invasive therapy for achalasia. It has now been widely accepted as an efficacious therapy, especially in view of the limitations of the current alternative endoscopic and surgical options as discussed above. Multiple studies from the United States, Asia and Europe have shown that POEM is an effective and safe procedure for achalasia when performed by experienced operators with adequate clinical response in 80–90% of patients [7 ,8–12,13 ,14]. Nonetheless, POEM requires a demanding skill set that involves both advanced endoscopic skills and knowledge of surgical anatomy. In addition, the endoscopist must have the capability to manage procedural complications. &
&
FIGURE 1. Endoscope setup for jet injection of dyed saline. One bottle of saline and a second bottle of saline mixed with indigo carmine are directly connected to the water jet channel via a stopcock. The former is used to clear endoscopic view whereas the latter is used for staining submucosal fibers during tunneling. Separate foot paddles control injection of either pure saline for optimizing visual field or dyed saline for submucosal tunneling.
Operative technique
coagulation mode at 50 W on effect 2 (ERBE). Repeated jet injection of saline mixed with indigo carmine is performed to enhance the demarcation between the submucosal layer and the muscularis propria whenever the submucosal dissection plane becomes unclear (Fig. 2). Large vessels in the submucosa are coagulated using the Coagrasper (Olympus) in soft coagulation mode at 80 W on effect 5 (ERBE) (Fig. 3).
A high-definition gastroscope fitted with a transparent cap is used. A gastroscope with a dedicated integrated water jet channel is recommended. One bottle of saline and a second bottle of saline mixed with indigo carmine are directly connected to the water jet channel via a stopcock. Separate foot pedals control each bottle (Fig. 1). Carbon dioxide insufflation is used during the entire length of the procedure and intravenous antibiotics are initially administered. The level of the lower esophageal sphincter (LES) is identified and dictates at which level the submucosal tunneling is initiated. A submucosal bleb is then created 3 cm above the level of the proximal margin of the proposed myotomy using 0.9% saline, 0.01% epinephrine and 0.25% indigo carmine solution. A 1.5–2 cm longitudinal mucosal incision is made with a triangular tip knife (KD 640L, Olympus) using dry cut mode at 50 W on effect 3 (ERBE, Tubingen, Germany). The endoscope is then maneuvered into the submucosal space and the triangular tip knife is used to dissect the submucosal fibers using spray
FIGURE 2. Repeated jet injection (arrow) of dyed saline is performed during submucosal tunneling to improve the demarcation between the submucosal layer and muscularis propria whenever the submucosal dissection plane becomes unclear.
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FIGURE 3. Large vessel seen within the submucosal tunnel.
Care should be taken with orientation of the endoscope to ensure the mucosal layer is not injured during dissection as the submucosal tunnel is extended, passing the LES and extending 2–3 cm into the proximal stomach (Fig. 4). Subsequently, myotomy of the inner circular muscle bundles is performed starting 2 cm distal to the mucosal entry point. The sharp tip of the triangular tip knife is used to catch single circular muscle bundles, lift them toward the tunnel, followed by cutting with spray coagulation current at 50 W on effect 2 (ERBE) (Fig. 5). Mucosal entry is then closed using endoscopic clips (Fig. 6) [15].
Determination of adequacy of myotomy length Multiple standard methods can be implemented to aid in correct localization of the gastroesophageal
FIGURE 4. Submucosal tunnel after the submucosal fibers have been dissected away. The myotomy can now be commenced. 446
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FIGURE 5. Selective myotomy of the circular muscle fibers (a). The longitudinal muscle fibers (b) have been preserved.
junction (GEJ) during POEM and these include insertion depth, resistance of passage of the endoscope through the GEJ, change in vasculature and injection of epinephrine. Many of these methods are subjective. Our preference is to use the transillumination technique. After creation of a submucosal tunnel along the distal esophagus and cardia, the gastroscope is removed and an ultraslim, 5.9-mm gastroscope is inserted through the mouth into the upper esophagus. The gastroscope is reinserted through the mouth alongside the ultraslim gastroscope. The gastroscope is advanced to the level of the mucosal incision. Under endoscopic visualization, the ultraslim endoscope is advanced through the mucosal incision into the submucosal space and then to the most distal aspect of the tunnel. The gastroscope is then advanced to the proximal stomach. The light intensity of the gastroscope is
FIGURE 6. Closure of the mucosal entry on the anterior esophageal wall with four endoscopic clips. Volume 30 Number 5 September 2014
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decreased while transillumination is turned on for the ultraslim endoscope. The transillumination light is visualized with the gastroscope, which enables exact identification of the extent of the tunnel into the gastric cardia (Fig. 7) [16]. At least 2 cm of cardia myotomy is required for effective POEM.
Postoperative care All patients are subsequently admitted for inpatient hospital observation. Twice-daily proton pump inhibitors, broad-spectrum antibiotics and prophylactic antiemetics are prescribed. Esophagram is obtained the following day and soft diet is commenced after esophageal leak is excluded. Patients are advised to remain on soft diet for 2 weeks; after that a regular diet can be started. Follow-up includes clinic visits to assess for delayed complications and clinical response (Eckardt score) in addition to esophageal acid exposure testing and repeat highresolution esophageal manometry.
Selective inner circular versus full-thickness myotomy A selective inner circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during POEM, which is different from the usual full-thickness myotomy performed surgically. Although selective circular muscle myotomy is designed to avoid entering the pleural space and decrease morbidity, it is often hard to achieve because the longitudinal muscle
FIGURE 7. Transillumination can be seen 2 cm below the gastroesophageal junction indicating that the submucosal tunnel is of an ample length to facilitate an adequate cardiomyotomy.
fibers of the esophagus are extremely thin, which frequently leads to an unintentional splitting of the muscle fibers during POEM (Fig. 8). Either minor electrocautery damage, mechanical trauma from maneuvering the endoscope in the tunnel, or CO2 insufflation alone can result in spreading of the longitudinal muscle fibers and adventitia and transmural openings into the mediastinum [15]. Moreover, the plane of separation between circular and longitudinal muscular layers becomes difficult to delineate at the level of the GEJ and stomach. Some operators also believe that full-thickness myotomy is a prerequisite for sufficient and long-term reduction of LES pressure and that it may reduce the incidence of fusion by further spreading of the cut muscular wall and theoretically inducing long-term symptom remission. Li et al. [17 ] compared outcomes (symptom relief, procedure-related parameters and adverse events, manometry outcomes and reflux complications) between 103 patients who underwent full-thickness myotomy (group A) and 131 patients who underwent selective inner circular muscle myotomy (group B). The mean operative times were significantly shorter in group A compared with group B (42 min vs. 49 min, P ¼ 0.02). There was no difference in the rate of adverse events between both groups (all P < 0.05). During follow-up, treatment success (Eckardt score 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (P ¼ 0.75). There were no statistically significant differences in pretreatment and posttreatment symptom scores and LES pressures between groups (both P > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs. 16.5%, P ¼ 0.38). The authors &&
FIGURE 8. Splitting of the longitudinal muscle fibers despite attempted selective cardiomyotomy. The pleura can be seen through the translucent adventitia.
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concluded that symptom relief and manometry outcomes of both methods were comparable. In addition, full-thickness myotomy rendered POEM more efficient with increase in procedure-related adverse events or reflux complications [17 ]. We believe that performing selective inner circular myotomy adds a ‘safety net’ to the procedure and may assist in safer dissemination of POEM, especially when it is performed by less experienced operators. &&
Triangular tip knife versus hybridKnife Most POEM operators use a triangular tip knife to dissect the submucosal layer and also to divide the circular muscle. The use of a triangular tip knife with an electrosurgical energy generator (VIO 300D, ERBE) enables a spray-coagulation mode with noncontact tissue dissection. Spray coagulation mode renders the submucosal dissection during tunnel creation much easier, faster and with less bleeding [18]. The shortcoming of the triangular tip knife is that it does not allow for injection of dyed saline to stain submucosal fibers. This results in frequent exchange of devices and prolongs procedural times. The use of the hybridKnife (ERBE) can overcome these limitations of the triangular tip knife as it allows for high-pressure water jet for needleless submucosal injection and electrosurgical interventions, such as submucosal tunneling and endoscopic myotomy of inner circular muscle bundles. One randomized controlled trial showed that the hybridKnife led to significantly shorter operative times as compared with standard technique using the triangular tip knife. This was mainly because of significant decrease in the mean number of instrument exchanges needed during the procedure (2 vs. 19.2, P < 0.0001) [19 ]. Nonetheless, most POEM operators worldwide use the triangular tip knife for both submucosal tunneling and endoscopic myotomy. In addition, the hybridKnife does not permit reliable spray-coagulation mode with noncontact tissue dissection (Fig. 9). We have shown that direct jet injection of dyed saline through the dedicated channel of the gastroscope results in adequate, consistent and reliable staining of submucosal fibers, which renders submucosal dissection accurate, efficient and safe [20 ]. The use of our simple technique offers the advantage of decreased need for instrument exchanges with continued use of the triangular tip knife, which has the advantage of allowing for spray coagulation [20 ]. A prerequisite to our technique is availability of a gastroscope with a dedicated water jet channel. We &&
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FIGURE 9. (a) Dissection of the submucosal fibers using spray coagulation with the triangular tip knife. (b) Submucosal tunneling using the hybridKnife which allows for both submucosal dissections in addition to fluid injection into the submucosal space.
use the GIF-HQ190 (Olympus) for this purpose. Another advantage of this endoscope is its slim tip diameter of 9.2 mm, which allows for better manipulation inside the narrow submucosal tunnel. In addition, the dual focus feature of the GIF-HQ190 endoscope allows the endoscopist to select from two focus settings (near field or normal field), which aids in precise identification of the layers, including differentiating inner circular muscle fibers from outer longitudinal ones. Other gastroscopes with dedicated water jet channels are also available and include GIF-H180J (Olympus) and EG2990i and EG2990k (Pentax Medical Corp., Montvale, New Jersey, USA) gastroscopes. We also believe that a dedicated water channel is an essential feature for safe POEM procedures as it ensures clear endoscopic view, especially during bleeding inside the narrow submucosal tunnel with limited visibility and maneuverability, while permitting dedicated use of the therapeutic channel for hemostasis. Volume 30 Number 5 September 2014
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Anterior versus posterior myotomy Most endoscopists use the anterior approach described in the first study by Inoue et al. In fact, the international POEM survey [21], which inspected 16 international expert centers, showed that 14 of 16 centers preferred the anterior approach. The LES in humans has multiple components that include a weaker thinner clasp (circular) part on the gastric lesser curvature centered at 2 o’clock with 12 o’clock defined as the most anterior point and a sling (oblique) fiber part centered on the left posterior lateral wall of the LES at 7 o’clock and draping over the anterior and posterior walls at 5 and 11 o’clock, respectively. The sling fibers represent a significant barrier to reflux. LHM usually involves transection of the sling fibers at 11 o’clock and thus reflux symptoms are common afterwards. On the other hand, most POEM operators begin the submucosal tunnel at 2 o’clock which may minimize postprocedure reflux, but the tradeoff is theoretical suboptimal efficacy because LES disruption is the key factor in achalasia intervention [22]. Some expert POEM operators believe that a predominant 5 o’clock myotomy may result in a better relief of dysphagia because of dissection of the sling fibers but at the expense of potentially higher rates of reflux [22]. This belief is debatable and a randomized controlled trial is needed to study the best approach to POEM.
Peroral endoscopic myotomy versus laparoscopic Heller myotomy A few studies compared perioperative outcomes between POEM and LHM and showed similar efficacy and safety despite inclusion of the initial POEM procedures performed at the respective centers [7 ,23–25]. More recently, Bhayani et al. [26 ] prospectively compared outcomes (swallowing function, operative time, complication and gastroesophageal reflux disease) of 64 patients who underwent LHM and 37 patients who underwent POEM. Median operative time (149 vs. 120 min, P < 0.001) and mean length of hospital stay (2.2 vs. 1.1 days, P < 0.0001) were significantly higher for LHM. Postoperative morbidity was comparable. One-month Eckardt scores were significantly better for POEM (1.8 vs. 0.8, P < 0.0001). At 6 months, both groups had sustained similar improvements in their Eckardt scores (1.7 vs. 1.2, P ¼ 0.1). Both groups had significant improvements in postmyotomy lower esophageal sphincter profiles. Postmyotomy resting pressures were higher for POEM than for LHM (16 vs. 7.1 mmHg, P ¼ 0.006). Postoperatively, 39% of POEM patients and 32% of &
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LHM patients had abnormal acid exposure (P ¼ 0.7). The authors concluded that POEM is comparable with LHM for safe and effective treatment of achalasia [26 ]. It is interesting that although the study above showed comparable long-term results for LHM and POEM, examination of individual symptoms showed significantly less dysphagia to solids that is present early after surgery and persists even up to six months in patients who underwent POEM. The authors speculated that LHM by nature involves manipulation of the GEJ and gastric fundus, and this trauma, operative edema and the concomitant fundoplication probably explain the higher rate of dysphagia to solids in the early postoperative period. &&
Peroral endoscopic myotomy in patients post-Heller myotomy Recurrence or persistence of symptoms occurs in approximately 20% of patients after Heller myotomy for achalasia. Three studies have examined the use of POEM in patients who are postHeller myotomy. Zhou et al. [27] prospectively studied 12 patients with recurrence or persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of at least 4. All 12 patients underwent successful POEM after a mean of 12 years from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months, treatment success was achieved in 11 or 12 patients (91.7%; mean score pretreatment vs. posttreatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pretreatment and 13.5 mmHg posttreatment (P < 0.001). Similarly, Onimaru et al. [28] studied 11 patients who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment. Pneumatic dilation alone was effective in one patient, and in the remaining ten patients, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in LES resting pressures (22.1 vs. 10.9 mmHg, P < 0.01) and Eckardt symptom scores (6.5 vs. 1.1, P < 0.001) were observed. Most recently, Vigneswaran et al. [23] reported five patients who underwent POEM after failed LHM. The mean operative time was 149 min. All patients responded with significant decrease in mean postoperative Eckardt score (6.8 vs. 0.6, P ¼ 0.0004). Therefore, POEM seems to be a viable treatment option for patients with recurrent or persistent symptoms after LHM when performed by experienced operators.
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Peroral endoscopic myotomy for spastic esophageal disorders In the current iteration of the Chicago classification of esophageal motility disorders, spastic esophageal disorders include spastic (type III) achalasia, diffuse esophageal spasm (DES) and hypercontractile (jackhammer) esophagus. Although POEM is typically performed for the treatment of achalasia, it is potentially an ideal endoscopic therapy for refractory spastic esophageal disorders (SED), as it not only allows myotomy of the LES but also of the more proximal esophagus, where the hypertensive contractions occur. Shiwaku and Inoue previously reported successful treatment of a patient with DES by POEM in which a 17 cm myotomy was performed [29]. Sharata et al. [9] reported successful treatment of two patients with DES and four patients with nutcracker esophagus by POEM. We have previously reported on successful treatment of a patient with Jackhammer esophagus using POEM and suggested POEM as a platform for the treatment of SED refractory to medical therapy [30 ]. We propose that POEM with extensive myotomy plays an important role in spastic esophageal cases with treatment failure. &&
Gastric peroral endoscopic myotomy (endoscopic pyloromyotomy) We have previously described the first human endoscopic pyloromyotomy for refractory gastroparesis. Gastric peroral endoscopic myotomy (G-POEM) is feasible and can be performed using similar techniques to esophageal POEM. Subsets of patients with refractory gastroparesis are likely to benefit from this novel endoscopic approach to gastroparesis therapy. Methods to identify these patients are needed. These may include initial placement of transpyloric stents, injection of botulinum toxin (with avoidance of posterior wall) or electrogastrography [31].
resection. Enucleation of SET was performed by dissection of connected muscle fibers followed by suctioning of mobilized tumor into the cap device, and then pulling it out through the mucosal entry. Lastly, the mucosal incision was tightly closed with endoscopic clips. All tumors were resected completely and no complications occurred. The mean procedure time was 150 min (range 40–365 min). Xu et al. [33] also described STER in 15 patients with SET originating from the muscularis propria in the esophagus and stomach. The average lesion size was 19 mm (range 12–30 mm) and average procedure time was 78.7 min (25–130 min). All lesions were successfully resected with lateral and vertical free margins. Air was used as the insufflating gas in this study. One patient developed pneumothorax requiring chest tube placement and one patient developed limited pneumoperitoneum requiring needle aspiration. More recently, Lee et al. [34] reported a case of full-thickness resection of a gastric SET using the STER technique. We have successfully performed a STER for the removal of a 6 cm leiomyoma in the mid-esophagus. The lesion was dissected within the submucosal tunnel using a triangular tip knife and subsequently extracted. (Fig. 10). Kobara et al. [35] recently used submucosal endoscopy to obtain core biopsies from gastric SET (mean size 20.2 mm, range 12–45 mm) originating from the muscularis propria in eight patients. One patient with gastric SET presenting primarily with extralumenal growth was excluded because of high risk for full-thickness perforation. A 10 mm
SUBMUCOSAL TUNNELING AND ENDOSCOPIC RESECTION STER technique of subepithelial tumors (SET) of the esophagus and stomach was recently described based on concepts of submucosal tunneling and flap closure [32]. Inoue et al. [5] performed STER in seven patients with SET (12–30 mm in size, all originating from the muscularis propria) of the esophagus or gastric cardia using ESD knives. Mucosal incision was performed 5 cm orally to the tumor after submucosal injection with saline and indigo carmine. Submucosal tunneling was then performed using spray coagulation and was extended beyond the tumor to secure enough working space for tumor 450
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FIGURE 10. Submucosal tunneling and endoscopic resection of a 6 cm esophageal leiomyoma. (a) The lesion within the tunnel after dissection from the muscularis propria. (b) The empty submucosal space after the lesion has been extracted from the tunnel. Volume 30 Number 5 September 2014
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transverse submucosal incision was performed 10 mm proximal to the tumor, followed by submucosal dissection and formation of a short tunnel (10 mm). Tumor was visually identified, exposed, and a core biopsy was obtained using combination of ESD knife and biopsy forceps. The authors used a cap designed to be longer at the tip and clipped the mucosal incision starting at tumor side (i.e., distal side). Both maneuvers were undertaken in an attempt to prevent contact between tumor and inner wall of the tunnel to avoid tumor seeding. All procedures were successfully performed with acquisition of core biopsies with a mean procedure time of 49.9 min (range 19–90 min). Immunohistochemical staining revealed six gastrointestinal stromal tumors (GISTs), one leiomyoma and one ectopic pancreas. Three GISTs were resected using hybrid NOTES approach and histologic assessment showed no tumor seeding within the short submucosal tunnels. STER is an evolving technique with more recent reports assessing its feasibility, efficacy and safety. It is a technically challenging procedure especially when resecting larger gastric lesions originating from the muscular layer. Challenges include narrowness of the submucosal tunnel, increased vascularity of the submucosal space on the gastric side, the vascularity of GISTs, difficulty in maintaining orientation, intricacy of dissection around the distal aspect of the tumor to create adequate working space and the need to avoid puncture of the tumor capsule (with GISTs).
CONCLUSION In conclusion, accessing and working within the wall of the gut is now feasible using techniques and lessons learnt from NOTES, ESD and endoscopic mucosal resection. POEM and STER offer minimally invasive and effective treatment alternatives for patients with achalasia, SED and upper gastrointestinal tumors originating from the muscularis propria. Other applications of submucosal endoscopy in the future can include sampling of the enteric nervous system and muscle, implantation of devices (such as microstimulators and drug delivery pumps), and bulking agents for reflux and incontinence. Acknowledgements None. Conflicts of interest M.A.K. is a consultant for Boston Scientific and Olympus America and has received research support from Cook Medical. All other authors have no conflicts of interest to disclose.
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Endoscopy 22. Friedel D, Modayil R, Iqbal S, et al. Per-oral endoscopic myotomy for achalasia: an American perspective. World J Gastrointest Endosc 2013; 5:420–427. 23. Vigneswaran Y, Yetasook AK, Zhao JC, et al. Peroral endoscopic myotomy (POEM): feasible as reoperation following Heller myotomy. J Gastrointest Surg 2014; 18:1071–1076. 24. Hungness ES, Teitelbaum EN, Santos BF, et al. Comparison of perioperative outcomes between peroral esophageal myotomy (POEM) and laparoscopic Heller myotomy. J Gastrointest Surg 2013; 17:228–235. 25. Teitelbaum EN, Rajeswaran S, Zhang R, et al. Peroral esophageal myotomy (POEM) and laparoscopic Heller myotomy produce a similar short-term anatomic and functional effect. Surgery 2013; 154:885–891. 26. Bhayani NH, Kurian AA, Dunst CM, et al. A comparative study on compre&& hensive, objective outcomes of laparoscopic Heller myotomy with per-oral endoscopic myotomy (POEM) for achalasia. Ann Surg 2014; 259:1098– 1103. This was a prospective comparative study of POEM and Heller myotomy and suggested equal efficacy and safety of both procedures with some advantages of POEM that included shorter hospital stays, shorter procedure times and less solid food dysphagia postoperatively. 27. Zhou PH, Li QL, Yao LQ, et al. Peroral endoscopic remyotomy for failed Heller myotomy: a prospective single-center study. Endoscopy 2013; 45:161–166. 28. Onimaru M, Inoue H, Ikeda H, et al. Peroral endoscopic myotomy is a viable option for failed surgical esophagocardiomyotomy instead of redo surgical Heller myotomy: a single center prospective study. J Am Coll Surg 2013; 217:598–605.
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29. Shiwaku H, Inoue H, Beppu R, et al. Successful treatment of diffuse esophageal spasm by peroral endoscopic myotomy. Gastrointest Endosc 2013; 77:149–150. 30. Khashab MA, Saxena P, Kumbhari V, et al. Peroral endoscopic myotomy && as a platform for the treatment of spastic esophageal disorders refractory to medical therapy (with video). Gastrointest Endosc 2014; 79:136– 139. This article described the expanded use of POEM to treat various spastic esophageal disorders refractory to medical therapy. 31. Khashab MA, Stein E, Clarke JO, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis: first human endoscopic pyloromyotomy (with video). Gastrointest Endosc 2013; 78:764–768. 32. Khashab MA, Pasricha PJ. Conquering the third space: challenges and opportunities for diagnostic and therapeutic endoscopy. Gastrointest Endosc 2013; 77:146–148. 33. Xu MD, Cai MY, Zhou PH, et al. Submucosal tunneling endoscopic resection: a new technique for treating upper GI submucosal tumors originating from the muscularis propria layer (with videos). Gastrointest Endosc 2012; 75:195– 199. 34. Lee CK, Lee SH, Chung IK, et al. Endoscopic full-thickness resection of a gastric subepithelial tumor by using the submucosal tunnel technique with the patient under conscious sedation (with video). Gastrointest Endosc 2012; 75:457–459. 35. Kobara H, Mori H, Fujihara S, et al. Bloc biopsy by using submucosal endoscopy with a mucosal flap method for gastric subepithelial tumor tissue sampling (with video). Gastrointest Endosc 2013; 77:141–145.
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Submucosal endoscopy: the new frontier of therapeutic endoscopy Mouen A. Khashab, Ahmed A. Messallam, Mohamad El Zein, and Vivek Kumbhari
Purpose of review Peroral endoscopic myotomy (POEM) and submucosal tunneling and endoscopic resection (STER) have been recently described as minimally invasive therapies for achalasia and gastrointestinal subepithelial tumors originating from the muscularis propria, respectively. This review illustrates the latest developments in the field of submucosal endoscopy, focuses on POEM and sheds light on STER. Recent findings Multiple studies from the United States, Asia and Europe have shown that POEM is an effective and safe procedure for achalasia when performed by experienced operators with adequate clinical response in 80–90% of patients. Nonetheless, POEM requires a demanding skill set that involves both advanced endoscopic skills and knowledge of surgical anatomy. In addition, the endoscopist must have the capability to manage procedural complications. Similarly, STER appears to be an effective therapy for treatment of small and medium sized gastrointestinal tumors originating from the muscularis propria. Summary POEM and STER offer minimally invasive and effective treatment alternatives for patients with achalasia, spastic esophageal disorders and upper gastrointestinal tumors originating from the muscularis propria. Keywords achalasia, botox, myotomy, peroral endoscopic myotomy, pneumatic dilation
INTRODUCTION Recent advances in natural orifice translumenal endoscopic surgery (NOTES) [1] and the improvement of devices for endoscopic submucosal dissection (ESD) have culminated in submucosal endolumenal approaches to treat achalasia using peroral endoscopic myotomy (POEM) technique. Submucosal tunneling was initially described by Sumiyama et al. [2], whereas POEM was first described by Pasricha et al. [3] in 2007 in a swine model. Inoue championed translating this innovative procedure into clinical care [4]. Inoue and other investigators have also used the submucosal space to access tumors that arise from the muscularis propria for either sampling or resection of these tumors [submucosal tunneling and endoscopic resection (STER)] [5]. This review illustrates the latest developments in the field of submucosal endoscopy, focuses on POEM and sheds light on STER.
PERORAL ENDOSCOPIC MYOTOMY Traditional endoscopic therapies of achalasia include botulinum toxin injection and pneumatic www.co-gastroenterology.com
dilation, whereas laparoscopic Heller myotomy (LHM) remains the conventional surgical therapy. The use of botulinum toxin has fallen out of favor because of limited durability and potential for increasing risk of subsequent myotomy. A large portion of patients who undergo pneumatic dilation will relapse, mainly during the first year after treatment [6]. Perforation is the most important and serious complication of pneumatic dilation with an overall rate between 2 and 4%. As with pneumatic dilation, the efficacy of LHM decreases with longer follow-up periods. An antireflux operation is typically recommended with LHM because of high risk of postoperative reflux. This is associated with increased postoperative dysphagia [6]. Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Correspondence to Mouen A. Khashab, MD, Assistant Professor of Medicine, Director of Therapeutic Endoscopy, Johns Hopkins Hospital, 1800 Orleans St, Suite 7125 B, Baltimore, MD 21205, USA. Tel: +1 443 287 1960; e-mail: [email protected] Curr Opin Gastroenterol 2014, 30:444–452 DOI:10.1097/MOG.0000000000000102 Volume 30 Number 5 September 2014
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KEY POINTS POEM and STER have been recently described as minimally invasive therapies for achalasia and gastrointestinal subepithelial tumors originating from the muscularis propria, respectively. Multiple studies from the United States, Asia and Europe have shown that POEM is an effective and safe procedure for achalasia with adequate clinical response in 80–90% of patients. STER appears to be an effective therapy for treatment of small and medium sized gastrointestinal tumors originating from the muscularis propria.
POEM is the latest breakthrough as a minimally invasive therapy for achalasia. It has now been widely accepted as an efficacious therapy, especially in view of the limitations of the current alternative endoscopic and surgical options as discussed above. Multiple studies from the United States, Asia and Europe have shown that POEM is an effective and safe procedure for achalasia when performed by experienced operators with adequate clinical response in 80–90% of patients [7 ,8–12,13 ,14]. Nonetheless, POEM requires a demanding skill set that involves both advanced endoscopic skills and knowledge of surgical anatomy. In addition, the endoscopist must have the capability to manage procedural complications. &
&
FIGURE 1. Endoscope setup for jet injection of dyed saline. One bottle of saline and a second bottle of saline mixed with indigo carmine are directly connected to the water jet channel via a stopcock. The former is used to clear endoscopic view whereas the latter is used for staining submucosal fibers during tunneling. Separate foot paddles control injection of either pure saline for optimizing visual field or dyed saline for submucosal tunneling.
Operative technique
coagulation mode at 50 W on effect 2 (ERBE). Repeated jet injection of saline mixed with indigo carmine is performed to enhance the demarcation between the submucosal layer and the muscularis propria whenever the submucosal dissection plane becomes unclear (Fig. 2). Large vessels in the submucosa are coagulated using the Coagrasper (Olympus) in soft coagulation mode at 80 W on effect 5 (ERBE) (Fig. 3).
A high-definition gastroscope fitted with a transparent cap is used. A gastroscope with a dedicated integrated water jet channel is recommended. One bottle of saline and a second bottle of saline mixed with indigo carmine are directly connected to the water jet channel via a stopcock. Separate foot pedals control each bottle (Fig. 1). Carbon dioxide insufflation is used during the entire length of the procedure and intravenous antibiotics are initially administered. The level of the lower esophageal sphincter (LES) is identified and dictates at which level the submucosal tunneling is initiated. A submucosal bleb is then created 3 cm above the level of the proximal margin of the proposed myotomy using 0.9% saline, 0.01% epinephrine and 0.25% indigo carmine solution. A 1.5–2 cm longitudinal mucosal incision is made with a triangular tip knife (KD 640L, Olympus) using dry cut mode at 50 W on effect 3 (ERBE, Tubingen, Germany). The endoscope is then maneuvered into the submucosal space and the triangular tip knife is used to dissect the submucosal fibers using spray
FIGURE 2. Repeated jet injection (arrow) of dyed saline is performed during submucosal tunneling to improve the demarcation between the submucosal layer and muscularis propria whenever the submucosal dissection plane becomes unclear.
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FIGURE 3. Large vessel seen within the submucosal tunnel.
Care should be taken with orientation of the endoscope to ensure the mucosal layer is not injured during dissection as the submucosal tunnel is extended, passing the LES and extending 2–3 cm into the proximal stomach (Fig. 4). Subsequently, myotomy of the inner circular muscle bundles is performed starting 2 cm distal to the mucosal entry point. The sharp tip of the triangular tip knife is used to catch single circular muscle bundles, lift them toward the tunnel, followed by cutting with spray coagulation current at 50 W on effect 2 (ERBE) (Fig. 5). Mucosal entry is then closed using endoscopic clips (Fig. 6) [15].
Determination of adequacy of myotomy length Multiple standard methods can be implemented to aid in correct localization of the gastroesophageal
FIGURE 4. Submucosal tunnel after the submucosal fibers have been dissected away. The myotomy can now be commenced. 446
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FIGURE 5. Selective myotomy of the circular muscle fibers (a). The longitudinal muscle fibers (b) have been preserved.
junction (GEJ) during POEM and these include insertion depth, resistance of passage of the endoscope through the GEJ, change in vasculature and injection of epinephrine. Many of these methods are subjective. Our preference is to use the transillumination technique. After creation of a submucosal tunnel along the distal esophagus and cardia, the gastroscope is removed and an ultraslim, 5.9-mm gastroscope is inserted through the mouth into the upper esophagus. The gastroscope is reinserted through the mouth alongside the ultraslim gastroscope. The gastroscope is advanced to the level of the mucosal incision. Under endoscopic visualization, the ultraslim endoscope is advanced through the mucosal incision into the submucosal space and then to the most distal aspect of the tunnel. The gastroscope is then advanced to the proximal stomach. The light intensity of the gastroscope is
FIGURE 6. Closure of the mucosal entry on the anterior esophageal wall with four endoscopic clips. Volume 30 Number 5 September 2014
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The new frontier of therapeutic endoscopy Khashab et al.
decreased while transillumination is turned on for the ultraslim endoscope. The transillumination light is visualized with the gastroscope, which enables exact identification of the extent of the tunnel into the gastric cardia (Fig. 7) [16]. At least 2 cm of cardia myotomy is required for effective POEM.
Postoperative care All patients are subsequently admitted for inpatient hospital observation. Twice-daily proton pump inhibitors, broad-spectrum antibiotics and prophylactic antiemetics are prescribed. Esophagram is obtained the following day and soft diet is commenced after esophageal leak is excluded. Patients are advised to remain on soft diet for 2 weeks; after that a regular diet can be started. Follow-up includes clinic visits to assess for delayed complications and clinical response (Eckardt score) in addition to esophageal acid exposure testing and repeat highresolution esophageal manometry.
Selective inner circular versus full-thickness myotomy A selective inner circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during POEM, which is different from the usual full-thickness myotomy performed surgically. Although selective circular muscle myotomy is designed to avoid entering the pleural space and decrease morbidity, it is often hard to achieve because the longitudinal muscle
FIGURE 7. Transillumination can be seen 2 cm below the gastroesophageal junction indicating that the submucosal tunnel is of an ample length to facilitate an adequate cardiomyotomy.
fibers of the esophagus are extremely thin, which frequently leads to an unintentional splitting of the muscle fibers during POEM (Fig. 8). Either minor electrocautery damage, mechanical trauma from maneuvering the endoscope in the tunnel, or CO2 insufflation alone can result in spreading of the longitudinal muscle fibers and adventitia and transmural openings into the mediastinum [15]. Moreover, the plane of separation between circular and longitudinal muscular layers becomes difficult to delineate at the level of the GEJ and stomach. Some operators also believe that full-thickness myotomy is a prerequisite for sufficient and long-term reduction of LES pressure and that it may reduce the incidence of fusion by further spreading of the cut muscular wall and theoretically inducing long-term symptom remission. Li et al. [17 ] compared outcomes (symptom relief, procedure-related parameters and adverse events, manometry outcomes and reflux complications) between 103 patients who underwent full-thickness myotomy (group A) and 131 patients who underwent selective inner circular muscle myotomy (group B). The mean operative times were significantly shorter in group A compared with group B (42 min vs. 49 min, P ¼ 0.02). There was no difference in the rate of adverse events between both groups (all P < 0.05). During follow-up, treatment success (Eckardt score 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (P ¼ 0.75). There were no statistically significant differences in pretreatment and posttreatment symptom scores and LES pressures between groups (both P > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs. 16.5%, P ¼ 0.38). The authors &&
FIGURE 8. Splitting of the longitudinal muscle fibers despite attempted selective cardiomyotomy. The pleura can be seen through the translucent adventitia.
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concluded that symptom relief and manometry outcomes of both methods were comparable. In addition, full-thickness myotomy rendered POEM more efficient with increase in procedure-related adverse events or reflux complications [17 ]. We believe that performing selective inner circular myotomy adds a ‘safety net’ to the procedure and may assist in safer dissemination of POEM, especially when it is performed by less experienced operators. &&
Triangular tip knife versus hybridKnife Most POEM operators use a triangular tip knife to dissect the submucosal layer and also to divide the circular muscle. The use of a triangular tip knife with an electrosurgical energy generator (VIO 300D, ERBE) enables a spray-coagulation mode with noncontact tissue dissection. Spray coagulation mode renders the submucosal dissection during tunnel creation much easier, faster and with less bleeding [18]. The shortcoming of the triangular tip knife is that it does not allow for injection of dyed saline to stain submucosal fibers. This results in frequent exchange of devices and prolongs procedural times. The use of the hybridKnife (ERBE) can overcome these limitations of the triangular tip knife as it allows for high-pressure water jet for needleless submucosal injection and electrosurgical interventions, such as submucosal tunneling and endoscopic myotomy of inner circular muscle bundles. One randomized controlled trial showed that the hybridKnife led to significantly shorter operative times as compared with standard technique using the triangular tip knife. This was mainly because of significant decrease in the mean number of instrument exchanges needed during the procedure (2 vs. 19.2, P < 0.0001) [19 ]. Nonetheless, most POEM operators worldwide use the triangular tip knife for both submucosal tunneling and endoscopic myotomy. In addition, the hybridKnife does not permit reliable spray-coagulation mode with noncontact tissue dissection (Fig. 9). We have shown that direct jet injection of dyed saline through the dedicated channel of the gastroscope results in adequate, consistent and reliable staining of submucosal fibers, which renders submucosal dissection accurate, efficient and safe [20 ]. The use of our simple technique offers the advantage of decreased need for instrument exchanges with continued use of the triangular tip knife, which has the advantage of allowing for spray coagulation [20 ]. A prerequisite to our technique is availability of a gastroscope with a dedicated water jet channel. We &&
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FIGURE 9. (a) Dissection of the submucosal fibers using spray coagulation with the triangular tip knife. (b) Submucosal tunneling using the hybridKnife which allows for both submucosal dissections in addition to fluid injection into the submucosal space.
use the GIF-HQ190 (Olympus) for this purpose. Another advantage of this endoscope is its slim tip diameter of 9.2 mm, which allows for better manipulation inside the narrow submucosal tunnel. In addition, the dual focus feature of the GIF-HQ190 endoscope allows the endoscopist to select from two focus settings (near field or normal field), which aids in precise identification of the layers, including differentiating inner circular muscle fibers from outer longitudinal ones. Other gastroscopes with dedicated water jet channels are also available and include GIF-H180J (Olympus) and EG2990i and EG2990k (Pentax Medical Corp., Montvale, New Jersey, USA) gastroscopes. We also believe that a dedicated water channel is an essential feature for safe POEM procedures as it ensures clear endoscopic view, especially during bleeding inside the narrow submucosal tunnel with limited visibility and maneuverability, while permitting dedicated use of the therapeutic channel for hemostasis. Volume 30 Number 5 September 2014
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Anterior versus posterior myotomy Most endoscopists use the anterior approach described in the first study by Inoue et al. In fact, the international POEM survey [21], which inspected 16 international expert centers, showed that 14 of 16 centers preferred the anterior approach. The LES in humans has multiple components that include a weaker thinner clasp (circular) part on the gastric lesser curvature centered at 2 o’clock with 12 o’clock defined as the most anterior point and a sling (oblique) fiber part centered on the left posterior lateral wall of the LES at 7 o’clock and draping over the anterior and posterior walls at 5 and 11 o’clock, respectively. The sling fibers represent a significant barrier to reflux. LHM usually involves transection of the sling fibers at 11 o’clock and thus reflux symptoms are common afterwards. On the other hand, most POEM operators begin the submucosal tunnel at 2 o’clock which may minimize postprocedure reflux, but the tradeoff is theoretical suboptimal efficacy because LES disruption is the key factor in achalasia intervention [22]. Some expert POEM operators believe that a predominant 5 o’clock myotomy may result in a better relief of dysphagia because of dissection of the sling fibers but at the expense of potentially higher rates of reflux [22]. This belief is debatable and a randomized controlled trial is needed to study the best approach to POEM.
Peroral endoscopic myotomy versus laparoscopic Heller myotomy A few studies compared perioperative outcomes between POEM and LHM and showed similar efficacy and safety despite inclusion of the initial POEM procedures performed at the respective centers [7 ,23–25]. More recently, Bhayani et al. [26 ] prospectively compared outcomes (swallowing function, operative time, complication and gastroesophageal reflux disease) of 64 patients who underwent LHM and 37 patients who underwent POEM. Median operative time (149 vs. 120 min, P < 0.001) and mean length of hospital stay (2.2 vs. 1.1 days, P < 0.0001) were significantly higher for LHM. Postoperative morbidity was comparable. One-month Eckardt scores were significantly better for POEM (1.8 vs. 0.8, P < 0.0001). At 6 months, both groups had sustained similar improvements in their Eckardt scores (1.7 vs. 1.2, P ¼ 0.1). Both groups had significant improvements in postmyotomy lower esophageal sphincter profiles. Postmyotomy resting pressures were higher for POEM than for LHM (16 vs. 7.1 mmHg, P ¼ 0.006). Postoperatively, 39% of POEM patients and 32% of &
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LHM patients had abnormal acid exposure (P ¼ 0.7). The authors concluded that POEM is comparable with LHM for safe and effective treatment of achalasia [26 ]. It is interesting that although the study above showed comparable long-term results for LHM and POEM, examination of individual symptoms showed significantly less dysphagia to solids that is present early after surgery and persists even up to six months in patients who underwent POEM. The authors speculated that LHM by nature involves manipulation of the GEJ and gastric fundus, and this trauma, operative edema and the concomitant fundoplication probably explain the higher rate of dysphagia to solids in the early postoperative period. &&
Peroral endoscopic myotomy in patients post-Heller myotomy Recurrence or persistence of symptoms occurs in approximately 20% of patients after Heller myotomy for achalasia. Three studies have examined the use of POEM in patients who are postHeller myotomy. Zhou et al. [27] prospectively studied 12 patients with recurrence or persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of at least 4. All 12 patients underwent successful POEM after a mean of 12 years from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months, treatment success was achieved in 11 or 12 patients (91.7%; mean score pretreatment vs. posttreatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pretreatment and 13.5 mmHg posttreatment (P < 0.001). Similarly, Onimaru et al. [28] studied 11 patients who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment. Pneumatic dilation alone was effective in one patient, and in the remaining ten patients, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in LES resting pressures (22.1 vs. 10.9 mmHg, P < 0.01) and Eckardt symptom scores (6.5 vs. 1.1, P < 0.001) were observed. Most recently, Vigneswaran et al. [23] reported five patients who underwent POEM after failed LHM. The mean operative time was 149 min. All patients responded with significant decrease in mean postoperative Eckardt score (6.8 vs. 0.6, P ¼ 0.0004). Therefore, POEM seems to be a viable treatment option for patients with recurrent or persistent symptoms after LHM when performed by experienced operators.
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Peroral endoscopic myotomy for spastic esophageal disorders In the current iteration of the Chicago classification of esophageal motility disorders, spastic esophageal disorders include spastic (type III) achalasia, diffuse esophageal spasm (DES) and hypercontractile (jackhammer) esophagus. Although POEM is typically performed for the treatment of achalasia, it is potentially an ideal endoscopic therapy for refractory spastic esophageal disorders (SED), as it not only allows myotomy of the LES but also of the more proximal esophagus, where the hypertensive contractions occur. Shiwaku and Inoue previously reported successful treatment of a patient with DES by POEM in which a 17 cm myotomy was performed [29]. Sharata et al. [9] reported successful treatment of two patients with DES and four patients with nutcracker esophagus by POEM. We have previously reported on successful treatment of a patient with Jackhammer esophagus using POEM and suggested POEM as a platform for the treatment of SED refractory to medical therapy [30 ]. We propose that POEM with extensive myotomy plays an important role in spastic esophageal cases with treatment failure. &&
Gastric peroral endoscopic myotomy (endoscopic pyloromyotomy) We have previously described the first human endoscopic pyloromyotomy for refractory gastroparesis. Gastric peroral endoscopic myotomy (G-POEM) is feasible and can be performed using similar techniques to esophageal POEM. Subsets of patients with refractory gastroparesis are likely to benefit from this novel endoscopic approach to gastroparesis therapy. Methods to identify these patients are needed. These may include initial placement of transpyloric stents, injection of botulinum toxin (with avoidance of posterior wall) or electrogastrography [31].
resection. Enucleation of SET was performed by dissection of connected muscle fibers followed by suctioning of mobilized tumor into the cap device, and then pulling it out through the mucosal entry. Lastly, the mucosal incision was tightly closed with endoscopic clips. All tumors were resected completely and no complications occurred. The mean procedure time was 150 min (range 40–365 min). Xu et al. [33] also described STER in 15 patients with SET originating from the muscularis propria in the esophagus and stomach. The average lesion size was 19 mm (range 12–30 mm) and average procedure time was 78.7 min (25–130 min). All lesions were successfully resected with lateral and vertical free margins. Air was used as the insufflating gas in this study. One patient developed pneumothorax requiring chest tube placement and one patient developed limited pneumoperitoneum requiring needle aspiration. More recently, Lee et al. [34] reported a case of full-thickness resection of a gastric SET using the STER technique. We have successfully performed a STER for the removal of a 6 cm leiomyoma in the mid-esophagus. The lesion was dissected within the submucosal tunnel using a triangular tip knife and subsequently extracted. (Fig. 10). Kobara et al. [35] recently used submucosal endoscopy to obtain core biopsies from gastric SET (mean size 20.2 mm, range 12–45 mm) originating from the muscularis propria in eight patients. One patient with gastric SET presenting primarily with extralumenal growth was excluded because of high risk for full-thickness perforation. A 10 mm
SUBMUCOSAL TUNNELING AND ENDOSCOPIC RESECTION STER technique of subepithelial tumors (SET) of the esophagus and stomach was recently described based on concepts of submucosal tunneling and flap closure [32]. Inoue et al. [5] performed STER in seven patients with SET (12–30 mm in size, all originating from the muscularis propria) of the esophagus or gastric cardia using ESD knives. Mucosal incision was performed 5 cm orally to the tumor after submucosal injection with saline and indigo carmine. Submucosal tunneling was then performed using spray coagulation and was extended beyond the tumor to secure enough working space for tumor 450
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FIGURE 10. Submucosal tunneling and endoscopic resection of a 6 cm esophageal leiomyoma. (a) The lesion within the tunnel after dissection from the muscularis propria. (b) The empty submucosal space after the lesion has been extracted from the tunnel. Volume 30 Number 5 September 2014
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transverse submucosal incision was performed 10 mm proximal to the tumor, followed by submucosal dissection and formation of a short tunnel (10 mm). Tumor was visually identified, exposed, and a core biopsy was obtained using combination of ESD knife and biopsy forceps. The authors used a cap designed to be longer at the tip and clipped the mucosal incision starting at tumor side (i.e., distal side). Both maneuvers were undertaken in an attempt to prevent contact between tumor and inner wall of the tunnel to avoid tumor seeding. All procedures were successfully performed with acquisition of core biopsies with a mean procedure time of 49.9 min (range 19–90 min). Immunohistochemical staining revealed six gastrointestinal stromal tumors (GISTs), one leiomyoma and one ectopic pancreas. Three GISTs were resected using hybrid NOTES approach and histologic assessment showed no tumor seeding within the short submucosal tunnels. STER is an evolving technique with more recent reports assessing its feasibility, efficacy and safety. It is a technically challenging procedure especially when resecting larger gastric lesions originating from the muscular layer. Challenges include narrowness of the submucosal tunnel, increased vascularity of the submucosal space on the gastric side, the vascularity of GISTs, difficulty in maintaining orientation, intricacy of dissection around the distal aspect of the tumor to create adequate working space and the need to avoid puncture of the tumor capsule (with GISTs).
CONCLUSION In conclusion, accessing and working within the wall of the gut is now feasible using techniques and lessons learnt from NOTES, ESD and endoscopic mucosal resection. POEM and STER offer minimally invasive and effective treatment alternatives for patients with achalasia, SED and upper gastrointestinal tumors originating from the muscularis propria. Other applications of submucosal endoscopy in the future can include sampling of the enteric nervous system and muscle, implantation of devices (such as microstimulators and drug delivery pumps), and bulking agents for reflux and incontinence. Acknowledgements None. Conflicts of interest M.A.K. is a consultant for Boston Scientific and Olympus America and has received research support from Cook Medical. All other authors have no conflicts of interest to disclose.
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Volume 30 Number 5 September 2014
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