A comparative study of endoscopic full-thickness and partial-thickness myotomy using submucosal endoscopy with mucosal safety flap (SEMF) technique
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- Bonin, E.A., Moran, E., Bingener, J. et al. Surg Endosc (2012) 26: 1751. doi:10.1007/s00464-011-2105-3
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Esophageal myotomy using submucosal endoscopy with mucosal safety flap (SEMF) has been proposed as a new treatment of achalasia. In this technique, a partial-thickness myotomy (PTM) preserving the longitudinal outer esophageal muscular layer is advocated, which is different from the usual full-thickness myotomy (FTM) performed surgically. The aim of this study was to compare endoscopic FTM and PTM and analyze the outcomes of each method after a 4 week survival period.
Twenty-four pigs were randomly assigned into group A (FTM, 12 animals) and group B (PTM) to undergo endoscopic myotomy. Lower esophageal sphincter (LES) pressure was assessed using pull-through manometry. For statistical analysis we compared the average esophageal sphincter pressure values at baseline, after 2 weeks, and after 4 weeks between groups A and B. The P value was set as <0.05 for significance.
Eighteen animals were included for statistical analysis. Mean (SD) LES pressures were similar between groups A and B (nine animals each) at baseline [group A = 23 (10.4) mmHg; group B = 20.7 (8.7) mmHg; P = 0.79], after 2 weeks [group A = 19 (7.7) mmHg; group B = 21.8 (8.4) mmHg; P = 0.79], and after 4 weeks [group A = 22.6 (10.2) mmHg; group B = 20.7 (9) mmHg; P = 0.82]. LES pressures were significantly reduced in three animals after 4 weeks: one animal (1%) in group A and two animals (2.5%) in group B. An extended myotomy (3 cm below the cardia) was achieved in three animals and was responsible for the significant drop in LES pressure seen in the two animals from group B.
Esophageal myotomy using SEMF is a feasible yet challenging procedure in pigs. Full-thickness myotomy does not seem to be superior to partial-thickness myotomy as demonstrated by pull-through manometry. Endoscopic esophageal myotomy results are greatly influenced by obtaining adequate myotomy extension into the gastric cardia.
Surgical myotomy had been shown to provide superior long-term outcomes compared to endoscopic techniques for long-term treatment of achalasia [1, 2]. The laparoscopic modified Heller myotomy procedure has become the preferred surgical approach in the appropriately selected patient . This procedure involves a surgical incision splitting the longitudinal and circular muscles of the esophagus from the distal esophagus onto the proximal stomach while preserving the mucosa. Extension of the myotomy 3 cm below the esophagogastric junction (EGJ) has been demonstrated to enhance long-term benefit . In addition, partial fundoplication has been advocated since successful myotomy is associated with objective findings of GERD in 30–60% of patients [1, 5].
A new endoluminal approach using submucosal endoscopic dissection to perform a myotomy has been proposed . A pioneering experimental study in pigs examined the feasibility of esophageal myotomy using the submucosal endoscopy with mucosal safety flap (SEMF) technique . This technique has been recently translated into humans for the treatment of achalasia . In this novel technique, originally a submucosal space was created with high-pressure CO2 injection (using CO2 bursts) and balloon dissection. The esophageal myotomy is performed within and at the end of this space. The myotomy, offset from a mucosal entry point, is securely sealed with the overlying mucosal flap, which closes the submucosal working space. The technical modification proposed by this previously published endoscopic method consists of partial-thickness myotomy involving the internal circular muscular fibers to decrease morbidity.
In the current study we performed the SEMF technique to assess subtotal versus full-thickness myotomy in a swine model in the setting of a 1-month survival study. The aim was to analyze the outcomes of each method, hypothesizing that full-thickness myotomy would be superior in providing LES pressures.
Materials and methods
This 4 week survival, Institutional Animal Care and Use Committee–approved study used 24 domestic cross-breed Yorkshire swine that weighed 50–55 kg. Animals were randomly assigned into study groups using a permuted block system: group A animals were to undergo full-thickness myotomy (12 animals) and group B partial-thickness myotomy (12 animals). Animals were fasted for solid food for 24 h and underwent standard general anesthesia (xylazine, 3 mg/kg intramuscular; Telazol, 5 mg/kg intramuscular). Animals were intubated and continuously monitored. Anesthesia was maintained using inhaled 1–2% isoflurane.
Lower esophageal sphincter (LES) pressure pre- and postmyotomy was assessed through manometric recordings. Pressures were recorded using a three-lumen water-perfused manometry catheter system (Narco Bio-systems, Austin, TX, USA) perfused with distilled water using a low-compliance pneumohydraulic system. Pressures within the catheter were transmitted to an external transducer and recorded using an electronic interface. The catheter assembly was pulled through the LES region three times. Each manometry recording was undertaken after a diagnostic endoscopic procedure with measurement of the distance from the snout and the esophageal Z-line. The manometry catheter was advanced using endoscopic assistance. Manometric recordings of LES pressure were taken on baseline, 2 weeks, and 4 weeks after procedure.
Endoscopic myotomy procedure
Follow-up and data analysis
After the intervention, all animals were kept on a liquid diet (Ensure) for 48 h, progressing to softened diet on day 3 and then a normal diet as tolerated. All animals also received antibiotics for 5 days (enrofloxacin 10 mg/kg once a day) and antacid therapy for 30 days (omeprazole 40 mg bid). Follow-up endoscopy was performed initially 2 weeks later, again after 24 h fast, to record the postmyotomy LES pressures. At 4 weeks follow-up endoscopy was performed and a final set of LES pressures was recorded. The animals were euthanized after the procedure. Necropsy was performed to examine the thoracic, abdominal cavity, and operated site. Examined parameters at necropsy included presence of esophageal abnormalities and complications.
Other parameters such as intraoperative findings and clinical postoperative outcome were recorded. Endoscopic findings of the esophageal and gastric mucosal anatomy at follow-up were also recorded. Examined parameters at esophageal manometry included the pressure amplitudes obtained from each of the recording channels from three measurements at baseline, after 2 weeks, and after 4 weeks. For statistical analysis we compared the average pressure values at baseline, after 2 weeks, and after 4 weeks between groups A and B using a nonparametric test (Mann–Whitney test). Results were expressed as mean (SD). The P value was set as <0.05 for significance.
Endoscopic myotomy using SEMF was performed in all 24 animals. Pneumothorax was a major complication for both full- and partial-thickness myotomy techniques and required a protocol change to include premyotomy tube thoracostomy.
The first five animals developed bilateral/tension pneumothorax which required urgent tube thoracostomy. Significant ventilation and oxygenation impairment persisted and the animals did not survive the postsurgical anesthetic recovery period. The procedures described below were all done using prophylactic right tube thoracostomy before starting the endoscopic procedures. Also, CO2 was added for endoscopic insufflation. The chest tube was removed after finishing the endoscopic procedure while the animal was under anesthesia.
Of the 19 subsequent animals, three developed significant intraoperative hypoxia despite adequate right tube thoracostomy drainage. One of them died in the postanesthesia recovery room despite recovering from hypoxia and achieving adequate anesthetic criteria for extubation. The other two animals underwent contralateral chest needle air decompression followed by chest tube insertion and survived for the required 4 week period without further complications.
Manometry pressures at full-thickness and partial-thickness myotomy groups
Experimental groups (N)
Preoperative manometry pressures [mean (SD)]
Postoperative manometry pressures after 2 weeks [mean (SD)]
Postoperative manometry pressures after 4 weeks [mean (SD)]
Group A: full-thickness (12)
23 (10.4) mmHg
19 (7.7) mmHg
22.6 (10.2) mmHg
Group B: partial-thickness (12)
20.7 (8.7) mmHg
21.8 (8.4) mmHg
20.7 (9) mmHg
Major and minor complications related to the major components of the SEMF myotomy
Opening and closure of mucosal entry site
Small esophageal [8 (33%) animals] and gastric [4 (16%) animals] mucosal perforations at EGJ
Opening of the gastric serosa with pneumoperitoneum [1 (4%) animal]
Tearing of the entry site [4 (16%) animals]
Inadvertent opening of the pleuraa (pneumothorax) 8 (66%) of the 12 animals in partial-thickness group
Opening and closure of the mucosal entry site
Overall postoperative findings and complications related to endoscopic myotomy using SEMF technique
Minor findings and complications
Permanence of clips at the mucosal entry site after 4 weeks [4 (16%) animals]
Gastric mucosal ulceration at the cardia [one (4%) animal]
Erosive esophagitis [6 (25%) animals]
Presence of pneumoperitoneum and intra-abdominal fluid [1 (4%) animal]
Major findings and complications
Severe hypoxia due to bilateral/tension pneumothorax leading to death [5(20%) animals]
Abscess at myotomy site [1 (4%) animal]
In all animals submucosal balloon tunneling was readily and expeditiously performed within the posterior esophageal wall down to the EGJ. Blunt dissection was then performed using a biopsy forceps with periodic CO2 burst insufflations which resulted in predictable success. Small mucosal perforations occurred at the esophageal and gastric mucosa at the level of the EGJ in four animals due to the short catheter point on the dissecting balloon and the acute angulation of the anatomy at this level. In one animal the balloon dissected into the chest leading to laceration of the pleura and pneumothorax. The median tunnel length was 9 cm (range = 4–14). Limited tunnel length (≤6 cm) was observed in four animals.
Eighteen animals survived the initial 24 h postanesthesia recovery period and thrived well during the following 4 weeks before being euthanized for necroscopic examination. Adequate healing of the mucosal closure site with slight mucosal scarring was observed in all animals at endoscopic examination prior to euthanasia. Retained clips were found at the mucosal closure site in four animals. One animal developed gastric mucosal ulceration at the cardia with significant improvement after 4 weeks. Erosive esophagitis was documented in six animals (three partial-thicknesses and three full-thicknesses). At necropsy the only finding of concern was a localized abscess at the esophageal wall with no extension to the pleural cavity in one animal that had undergone a full-thickness myotomy. This animal had no clinically detectable signs of infection at follow-up. Air and clear peritoneal fluid was seen in one and two animals, respectively. At necropsy the tattoo site was found in all animals and an extended cardia myotomy was documented in three.
Submucosal endoscopy with mucosal safety flap (SEMF) myotomy has emerged as a scarless and less invasive surgical myotomy option for treatment of achalasia [6, 7]. Theoretical advantages are obviating the need for abdominal or thoracic access, faster recovery, less pain, and improved cosmesis. An important anatomic advantage is the elimination of dissection at the level of the diaphragmatic hiatus thereby preserving the phrenoesophageal ligaments, which may be beneficial to avoid postmyotomy reflux. Furthermore, a SEMF myotomy performed along the posterior esophageal wall, which is technically the easiest approach, allows the anterior wall to be surgically accessed for revision. The SEMF procedure has been recently translated into humans for the treatment of achalasia [8–10]. This feasibility study has confirmed the ability to clearly identify and successfully incise the internal circular muscular layers using currently available endoscopic devices, creating a safe partial myotomy. This procedure has been safely performed by a single operator in 56 patients with favorable functional results at short-term follow-up . Initial published experience in humans is more than encouraging despite a relatively short follow-up. Others are rapidly adopting this method.
The SEMF technique requires creation of an esophageal mucosal opening for access (despite the fact that opening of the esophageal mucosa has been regarded as a complication of surgical esophageal myotomy); however, no difference in outcomes is seen when an inadvertent defect is detected and properly closed. In our series, the most common complication of creating the mucosal opening was tearing and enlargement of the entry incision. Attempting to pass the endoscope into a suboptimally sized opening was responsible for most of the entry point tears. Closure of the mucosal entry point was challenged more by a wider rather than a longer defect. Lengthening of the mucosal entry point by tearing could theoretically limit the cephalad extent of the myotomy, which may or may not be a disadvantage. The finding of a localized abscess in one animal could have been related to contamination of the submucosal tunnel.
In the present animal series, pneumothorax was a recurrent complication. This expectedly occurred in all full-thickness myotomies but also in animals undergoing partial-thickness myotomy. Despite limitations of the pig model because of the pig’s thinner esophageal wall and closer pleural contact to the esophageal adventitia as compared to humans, inadvertent opening of the pleura had a significant impact on morbidity and mortality for this procedure and should be a cause for cautionary planning in human cases.
Esophageal myotomy itself is a surgically challenging procedure. Standard esophageal myotomy for achalasia is a complete splitting of the esophageal muscle fibers 7 cm above and 1–2 cm below the EGJ. Incomplete myotomy is a term used to describe a myotomy with limited extent and is attributed to 30% of dysphagia recurrence in patients with achalasia . The most critical measure for reducing dysphagia recurrence has been to deliberately extend distal myotomy 3 cm below the EGJ [4, 12]. The extended distal myotomy has been shown to reduce postoperative recurrent dysphagia compared to the 1–2 cm more common standard myotomy . This procedure is characterized by performing the myotomy below Belsey’s fat pad, a superficial landmark located at the esophageal junction level that distinguishes the starting point for the myotomy at the cardia, resulting in disruption of the complex crisscrossing muscular fibers that contribute to the LES sphincter mechanism. Careful dissection of this area is recommended to avoid bleeding and excessive cauterization.
In our experience, dissection of EGJ was one of the most critical, time-consuming, and difficult steps of the procedure. There was a trend to perform limited dissection at this area due to concerns for inadvertent gastric mucosal perforation and the anatomic challenge of the sharp angulation crossing into the cardia. The submucosal connective tissue was less responsive to balloon dissection, requiring supplemental gas and blunt dissection which was challenged by a less readily identifiable plane of dissection. In the two animals with inadvertent perforation of the gastric serosa, the resultant pneumoperitoneum could be managed conservatively with needle decompression, which could certainly translate into an easily performed step in human procedures. Successful dissection into the cardia side of the LES was predictably heralded by the presence of several large vessels extending across the submucosal plane, which interestingly correlates to human anatomy. These serve as a critical landmark in the distal SEMF dissection. The deliberate effort at extended dissection into the cardia later in the study resulted in ulceration of the cardia in one case. We attributed this to mechanical trauma to the gastric mucosal flap. Despite tattooing to ensure targeting the distal submucosal dissection, the tattoo was unequivocally reached in only two instances. Limited myotomy, tattoo marking more distal than intended, and loss of orientation during dissection were regarded as reasons for not finding the tattoo markings. We observed that the extension of myotomy beyond the LES seems to increase with experience, in our case after performing 15 procedures.
Finally, gastroesophageal reflux disease is a concern for patients undergoing myotomy. Although we have not performed a specific test to detect gastroesophageal reflux and the animals had normal peristaltic esophagus prior to procedure, distal esophagitis was seen in three animals that had partial-thickness and in three animals that had full-thickness myotomy as early as 4 weeks after the procedure. A second procedure using transoral gastroplication could be a future option for patients presenting with such complication .
Intraoperative manometry has been used for assessing completeness of myotomy by measuring any residual high pressure across the gastroesophageal junction. In the present series, the manometry results between the two groups did not favor either partial- or full-thickness myotomy. In fact, we observed significant reduction in LES pressure (manometric pressure below 5 mmHg) in only three animals. Interestingly, in two of these animals an extended myotomy (the tattoo site was identified) was achieved. As extended myotomy was performed in only 3 of the 18 animals, this would explain why most animals in this series did not reach significant reduction in LES pressure after myotomy.
In conclusion, the present study demonstrates that intraluminal endoscopic esophageal myotomy is a feasible yet challenging procedure, chiefly for obtaining adequate extension into the gastric cardia. Although full-thickness and partial-thickness myotomy were associated with pneumothorax requiring prophylactic thoracostomy tube drainage, this has not been seen in the current human experience, likely because of the anatomic differences in the thoracic compartment between the porcine model and human. Advanced endoscopic expertise is needed to achieve the necessary extended cardia myotomy.
The take home message for the surgeon is that the intraluminal approach to myotomy simplifies the entire procedure. Creating the submucosal tunnel is efficient and promptly allows access to the EGJ, where the most critical phase of the myotomy—extension into the gastric cardia—can be focused upon with careful dissection. Finally, with care to avoid trauma to the overlying mucosal flap, a predictably safe and simple completion to the procedure is possible.
The present study demonstrates that esophageal myotomy using SEMF is a feasible yet challenging procedure in the swine model. Full-thickness myotomy does not seem to be superior to partial-thickness myotomy as demonstrated by pull-through manometry. Endoscopic esophageal myotomy results are greatly influenced by obtaining adequate myotomy extension into the gastric cardia. Proper dissection and extension of myotomy beyond the LES seems to increase with experience.
This study was supported by a NOSCAR grant.
Dr. Gostout and the Developmental Endoscopy Unit receive research grants from Olympus America and Olympus Tokyo. Dr. Gostout is an advisor to Apollo Endosurgery; both he and the Mayo Foundation maintain an equity position in Apollo Endosurgery, Inc. Dr. Gostout and the Mayo Foundation hold intellectual property (patent) on the SEMF procedure and devices. Drs. Bonin, Moran, and Bingener as well as Mary Knipschield have no conflicts of interest or financial ties to disclose.