- Email: [email protected]
A Stepwise Approach and Early Clinical Experience in Peroral Endoscopic Myotomy for the Treatment of Achalasia and Esophageal Motility Disorders
A Stepwise Approach and Early Clinical Experience in Peroral Endoscopic Myotomy for the Treatment of Achalasia and Esophageal Motility Disorders Lee L Swanström, MD, FACS, Erwin Rieder, MD, Christy M Dunst, MD, FACS Peroral endoscopic myotomy (POEM) has recently been described in humans as a treatment for achalasia. This concept has evolved from developments in natural orifice translumenal endoscopic surgery (NOTES) and has the potential to become an important therapeutic option. We describe our approach as well as our initial clinical experience as part of an ongoing study treating achalasia patients with POEM. STUDY DESIGN: Five patients (mean age 64 ⫾ 11 years) with esophageal motility disorders were enrolled in an IRB-approved study and underwent POEM. This completely endoscopic procedure involved a midesophageal mucosal incision, a submucosal tunnel onto the gastric cardia, and selective division of the circular and sling fibers at the lower esophageal sphincter. The mucosal entry was closed by conventional hemostatic clips. All patients had postoperative esophagograms before discharge and initial clinical follow-up 2 weeks postoperatively. RESULTS: All (5 of 5) patients successfully underwent POEM treatment, and the myotomy had a median length of 7 cm (range 6 to 12 cm). After the procedure, smooth passage of the endoscope through the gastroesophageal junction was observed in all patients. Operative time ranged from 120 to 240 minutes. No leaks were detected in the swallow studies and mean length of stay was 1.2 ⫾ 0.4 days. No clinical complications were observed, and at the initial follow-up, all patients reported dysphagia relief without reflux symptoms. CONCLUSIONS: Our initial experience with the POEM procedure demonstrates its operative safety, and early clinical results have shown good results. Although further evaluation and long-term data are mandatory, POEM could become the treatment of choice for symptomatic achalasia. (J Am Coll Surg 2011;213:751–756. © 2011 by the American College of Surgeons) BACKGROUND:
esophageal junction (GEJ). Although this surgical intervention is now performed primarily by minimally invasive techniques,2,3 dissection of the LES still requires several abdominal incisions and some sort of surgical antireflux procedure, which is accompanied by a certain morbidity rate. A potentially less invasive endoscopic method for division of the LES, using a needle-knife to cut the esophageal muscle from the lumenal side, was described by Ortega and colleagues4 in 1980. Due to concerns about mediastinal contamination or the lack of physical separation of the muscle edges, this method has not been further pursued. More than 25 years later, intellectual efforts to push the boundaries of flexible endoscopy and natural orifice translumenal endoscopic surgery (NOTES) led to the development of a novel treatment modality for achalasia. Pasricha and colleagues5 initially described the feasibility of an endoscopic submucosal esophageal myotomy in a survival animal model. Others have demonstrated this technique together with endolumenal antireflux procedures in survival animals.6 The first report in humans was from Inoue
Esophageal achalasia is a motility disorder involving failure of the lower esophageal sphincter (LES) to relax in response to swallowing and aperistalsis of the esophageal body. There is no known underlying cause,1 although autoimmune reactions against the myenteric nerve plexi have been postulated. Therapy focuses on the forced relaxation of the LES by endoscopic or surgical means. Noninvasive procedures are primarily botulinum toxin injection or esophageal dilatation. Because only few randomized controlled trials have tried to define the optimal strategy, treatment still varies widely. Surgical esophagomyotomy very effectively disrupts the esophageal muscular layers at the gastroDisclosure information: Nothing to disclose. Received July 12, 2011; Revised September 8, 2011; Accepted September 8, 2011. From The Oregon Clinic, Division of GI and Minimally Invasive Surgery (Swanström, Dunst) and Legacy Health System (Rieder), Portland, OR. Correspondence address: Lee L Swanström, MD, FACS, Division of GI and Minimally Invasive Surgery, The Oregon Clinic, 1040 NW 22nd Ave, Suite 560, Portland, OR 97210. email: [email protected]
© 2011 by the American College of Surgeons Published by Elsevier Inc.
751
ISSN 1072-7515/11/$36.00 doi:10.1016/j.jamcollsurg.2011.09.001
752
Swanström et al
Peroral Endoscopic Myotomy
J Am Coll Surg
Step 1 Abbreviations and Acronyms
EGD GEJ LES NOTES POEM
⫽ ⫽ ⫽ ⫽ ⫽
esophagogastroduodenoscopy gastroesophageal junction lower esophageal sphincter natural orifice translumenal endoscopic surgery peroral endoscopic myotomy
and colleagues,7 who coined the term POEM (peroral endoscopic myotomy) and reported on favorable results in 17 achalasia patients. Based on the procedure described by Inoue and our own animal studies,8 we initiated a clinical study in October 2010 and describe the technical steps of and early outcomes of POEM as a less invasive treatment option for treatment of refractory achalasia and other esophageal motility disorders.
METHODS The IRB of the Legacy Health System, Portland, OR, approved an initial 5 patients to be included in a prospective clinical study evaluating the described POEM procedure for esophageal motility disorders requiring myotomy (trial number: NCT01302288, http://www.clinicaltrials.gov). Inclusion criteria for this trial were eligibility for elective Heller myotomy and age greater than 18 years. Exclusion criteria were previous esophageal or mediastinal surgery or a body mass index greater than 40 kg/m2. Previous interventions such as dilatation or botulinum toxin injection were not considered contraindications because they were no longer contraindicated for laparoscopic approaches. However, patients with massively dilated or sigmoid esophagus were not included in this initial series. All patients had physiology testing performed before surgery, including manometry, esophagogastroduodenoscopy (EGD), and timed barium swallow. A standardized validated symptom assessment form was administered to the patient before surgery at each subsequent visit;9 this tool includes a dysphagia score graded on a Lickert scale with grade 0 (absent), grade 1 or 2 (moderate), and grade 3 or 4 (severe). Endoscopic technique
Patients were placed on a clear liquid diet for 24 hours and given a single preoperative dose of a first generation cephalosporin. With the patient under general anesthesia and in the supine position, EGD was performed using a highresolution upper endoscope (GIF-H180J, Olympus) and carbon dioxide (CO2) insufflation (3 L/min). After preliminary surveillance, an overtube was placed and an angled dissection cap was mounted onto the endoscope to facilitate the submucosal view. Our stepwise approach to perform POEM is outlined below.
A site for mucosotomy that is approximately 7 to 10 cm proximal to the GEJ is identified. A submucosal “lift” is performed by injecting the right anterior lumenal side of the esophagus with 3 mL of saline mixed with epinephrine and methylene blue. The elevated mucosa is then incised longitudinally for 1.5 to 2 cm using a needle-knife cautery to enable submucosal insertion of the flexible endoscope (Fig. 1A). Step 2
The endoscope is then inserted into the submucosal space and an endoscopic tunnel is created. A combination of blunt dissection with the cap and careful electrocautery with a triangle-shaped tip needle-knife (TT-knife, Olympus) as shown in Figure 1B is used. CO2 insufflation and saline infusion facilitates the dissection. Hot biopsy forceps were used to coagulate larger submucosal vessels before dissection. The submucosal tunnel is created along the lesser curvature and extended below the LES onto the gastric cardia. A retroflexed view is used to ensure an adequate extension onto the stomach. Step 3
Dissection of only the inner circular muscle layer and sling fibers of the LES is carried out starting approximately 4 cm above the LES and extending 2 to 3 cm onto the gastric cardia. A special triangle-tip knife, designed for endoscopic submucosal dissection, was used with monopolar coagulation. A spray current of maximum 40 watts is used for the myotomy by lifting and dividing the muscle fibers, as demonstrated in Figure 1C. Radial tension from both the dissecting cap and the CO2 insufflation further facilitates division of the circular muscle fibers. When an appropriate myotomy is achieved, the flexible endoscope is withdrawn and smooth passage through the GEJ is evaluated. Step 4
After withdrawing the endoscope from the submucosal tunnel, the mucosal incision is closed by standard endoscopic hemoclips (Fig. 1D). Each patient had a postoperative gastrografin esophagogram on the first postoperative day and was started on a pureed diet, which was continued for 1 week after discharge. The initial clinical follow-up was arranged at 2 weeks.
RESULTS Patients
The 5 patients (2 women/3 men) had a median age of 67 years (range 49 to 78 years) and a median body mass index of 25.0 kg/m2 (range 23.7 to 27.1 kg/m2). Four of the 5 patients were previously diagnosed with achalasia, 3 of whom had hypertensive LES pressures (resting pressure of 55.1 mmHg (range 37.2 to 58.8 mmHg) and a median residual LES pressure of
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Figure 1. (A) Endoscopic view of the elevated mucosa, which is incised by needle-knife cautery to enable submucosal insertion of the flexible upper endoscope (dissection cap attached). (B) In the submucosal space an endoscopic tunnel is created mainly by careful electrocautery with a triangle-shaped tip needle-knife. Note the muscular layer visible on the left and the esophageal mucosa on the right of the endoscopic image (dissection cap attached). (C) Only the inner esophageal muscle fibers (*) are divided, using the triangle-shaped tip needle-knife (***). The intact outer longitudinal muscle layer (**) can be visualized (dissection cap attached to the endoscope). (D) The mucosal incision is closed by standard endoscopic clips. Note the remaining opening of the mucosa before complete closure.
36.5 mmHg (range 9.9 to 39.8 mmHg). Recent manometry data were not available for 1 patient, who had a more than 10-year history of achalasia and old motility reports confirming no motility and who had been treated several times with botulinum toxin injections and dilatations since his original diagnosis. Three other patients had previous botulinum toxin injections as well. One of the 5 patients was initially diagnosed as having achalasia, but on further studies in our laboratory was actually found to
have 30% peristalsis with distal esophageal spasm (distal esophageal contraction mean amplitude of 233 mmHg). A normal LES resting pressure with incomplete relaxation (16.8 mmHg) therefore led to the more accurate diagnosis of nutcracker esophagus with an incompletely relaxing LES. Endoscopic procedure
The initial mucosal incision was carried out at 9.2 cm (range 8 to 11 cm) above the GEJ and the subsequently
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Figure 2. The extension of the myotomy onto the stomach (3 cm) can be visualized and measured in retroflex endoscopic view.
created submucosal tunnel onto the lesser curvature had a median length of 10 cm (range 10 to 13 cm). The submucosal tunnel was dissected primarily by electrocautery using the triangle tip-shaped needle knife. Myotomy of the inner circular esophageal muscle fibers was achieved in all (5 of 5) cases, with a median length of 7.5 cm (range 6 to 12 cm). The longest myotomy was for the diffuse esophageal spasm/nutcracker patient. It was extended into the gastric cardia for 2 cm (range 1 to 3 cm). In 2 cases there was a small mucosal perforation in the gastric cardia. It did not interfere with the procedure and closure was made with standard endoscopic clips after the myotomy. There was no obvious breach of the longitudinal muscle layer, but this layer was observed to be very thin. Three patients (3 of 5) developed CO2 pneumoperitoneum diagnosed by clinical palpation of the abdominal wall. No patient was noted to have capnomediastinum. A Veress needle placed in the left upper quadrant under sterile conditions normalized the abdominal pressure in all 3 patients. After the myotomy but before mucosal closure, the endoscope was withdrawn from the submucosal tunnel and advanced through the GEJ. Smooth passage of the endoscope into the stomach was observed immediately after myotomy in all patients. The mucosal incision was successfully closed in all patients using an average of 7 clips. Retroflexion showed adequate extension of the dissection onto the gastric cardia in all cases (Fig. 2). Procedure time ranged from 120 to 240 minutes. Intraoperatively, the blood pressure, heart rate, and ventilation parameters remained in the normal range for the duration of the procedure. Early postoperative results
Water-soluble upper gastrointestinal x-rays were obtained on postoperative day 1 in all cases. There was no esophageal
Figure 3. Transnasal endoscopy at the initial 2-week postoperative follow-up shows a perfectly healed mucosa with the clips still in place.
leakage and there was free flow into the stomach in all cases. Patients were discharged on postoperative day 1 (mean length of stay was 1.2 ⫾ 0.4 days) by protocol and no clinical complications in the perioperative period were observed. At the 2-week clinical follow-up, all patients reported immediate symptom relief (dysphagia score of 0 or 1) and no need for postoperative pain medication. One patient agreed to have unsedated transnasal endoscopy at the first follow-up to assess the status of the esophageal closure. A perfectly healed esophageal mucosa was observed with the hemoclips still in place (Fig. 3).
DISCUSSION Shortly after the experimental animal studies of Pasricha and colleagues5 describing endoscopic methods of esophageal myotomy were reported, the surgeon H Inoue and associates demonstrated that this noninvasive technique was also applicable to humans with achalasia7 and other spastic esophageal motility disorders.10 Since October 2010 we have been performing peroral endoscopic myotomies in patients diagnosed with profound esophageal motility disorders under an IRB-approved trial. Our initial experience has shown that this is a safe and extremely effective therapy and that it deserves consideration as a primary treatment for the disease. All current treatments for esophageal achalasia have different advantages and draw-
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backs, so the ideal approach is still debated. Endoscopic balloon dilatation is still widely performed because of its relative noninvasiveness, but it has a lower success rate and often requires multiple treatments.11 It can also result in a substantial perforation rate. Laparoscopic myotomy is long established and is probably more definitive, but it is an invasive surgical procedure, which involves complete mobilization of the GEJ with subsequent requirement of an antireflux operation.12 The appeal of the POEM procedure is that it specifically targets, and allows surgical division of, only the muscle layers of the LES affected by achalasia, thereby preserving the anatomic integrity of the LES anatomy and possibly minimizing postoperative reflux. More than nearly 50% of laparoscopic Heller myotomy patients without a fundoplication will have pathologic reflux, and even as many as 10% of patients with a Heller and partial fundoplication will have problems,12 but early reports of the POEM procedure potentially indicate a lower incidence. Current data, including ours, clearly indicate the safety of the procedure. The only clinical relevant adverse event observed in our series was development of a pneumoperitoneum in 3 patients, resolved with placement of a Veress needle to decompress it. There were no postoperative consequences of this intervention. Inoue described this occurrence as well in 10% of his most recent series of more than 100 patients (personal communication) and theorized that it might occur due to gas permeation through the remarkably thin longitudinal muscle fibers of the esophagus. No pneumomediastinum was noted in our series. This, however, would usually not be considered a complication because during laparoscopic dissection at the hiatus, as it has a reported incidence as high as 85% but resolves within few days.13 A concern of this new approach is whether previous interventions (balloon dilatations or botulinum toxin injections) would be contraindicated due to a possibly higher incidence of complications.14-18 However, other authors have noticed no such problems.19 One patient in our clinical series had several balloon dilatations before surgery, and 3 patients had previous botulinum toxin therapy. We did not note any particular difficulty with these previously treated patients but our numbers are of course low. We tried to make all myotomies on the right anterior esophageal side along the lesser curvature. This approach was previously observed to be easier compared with a posterior myotomy.7 Others theorized the potential benefit of a posterior approach because a later anterior surgical myotomy could still be performed if recurrent symptoms occurred.20 All patients in our early series reported immediate symptom relief without the need for postoperative pain medication. Additionally, a postoperative transnasal EGD
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performed in one patient observed a perfectly healed mucosa at the 2-week follow-up. However, whether POEM is as effective as the current surgical “gold standard” has to be evaluated by further objective testing. Inoue and coworkers7 reported a 70% drop in the LES pressure in patients with nonsigmoid esophagi, and 50% drop in patients with sigmoid esophagi. A recent experimental study evaluating the postoperative decrease of the LES pressure found the endoscopic submucosal approach less effective than open myotomy.21 On the other hand, measurement of the GEJ distensibility found similar results in both groups. However, because this was a physiologic, nonachalasic model, comparisons to the clinical setting may not be valid. Weaknesses of our study include the small numbers and current lack of long-term follow-up. We will continue to accrue data prospectively and are in the process of obtaining comprehensive physiology studies at 6 months, including upper endoscopy, timed barium swallow, impedence/pH testing, and motility, as well as long-term (3-year) follow-up. We believe that the surgical community needs to be aware of this new and potentially better approach to achalasia as soon as possible so it can prepare training opportunities and prospective outcomes studies.
CONCLUSIONS We describe our initial clinical experience with 5 patients treated with POEM for esophageal dismotility disorders and report excellent outcomes and feasibility. These early results add more data on the safety and feasibility of this approach to the current literature. All our patients had immediate subjective symptom relief and no infectious complications. Notably, there was no pain related to the procedure, which also took no longer than a typical laparoscopic treatment. This seems to validate the initial promise of NOTES and, if long-term results are favorable, this may be the first NOTES procedure to achieve a “gold standard” status. Author Contributions
Study conception and design: Swanström, Rieder, Dunst Acquisition of data: Swanström, Rieder, Dunst Analysis and interpretation of data: Swanström, Rieder, Dunst Drafting of manuscript: Swanström, Rieder Critical revision: Swanström, Rieder, Dunst Acknowledgement: The authors thank Olympus, USA, for providing the high-resolution upper endoscope and endoscopic instrumentation.
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1. Gockel HR, Schumacher J, Gockel I, et al. Achalasia: will genetic studies provide insights? Hum Genet 2010;128:353–364. 2. Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology 2010;139:369–374. 3. Patti MG, Fisichella PM, Perretta S, et al. Impact of minimally invasive surgery on the treatment of esophageal achalasia: a decade of change. J Am Coll Surg 2003;196:698–703. 4. Ortega JA, Madureri V, Perez L. Endoscopic myotomy in the treatment of achalasia. Gastrointest Endosc 1980;26:8–10. 5. Pasricha PJ, Hawari R, Ahmed I, et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy 2007;39:761–764. 6. Perretta S, Dallemagne B, Allemann P, Marescaux J. Multimedia manuscript. Heller myotomy and intraluminal fundoplication: a NOTES technique. Surg Endosc 2010;24:2903. 7. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42:265–271. 8. Spaun GO, Dunst CM, Arnold BN, et al. Transcervical Heller myotomy using flexible endoscopy. J Gastrointest Surg 2010;14: 1902–1909. 9. Khajanchee YS, Kanneganti S, Leatherwood AE, et al. Laparoscopic Heller myotomy with Toupet fundoplication: outcomes predictors in 121 consecutive patients. Arch Surg 2005;140: 827–833. 10. Chiu PWY, Inoue H, Teoh AYB, et al. Per-oral endoscopic myotomy for treatment of hypertensive lower esophageal sphincter. Gastrointest Endosc 2011;73:AB 107. 11. Campos GM, Vittinghoff E, Rabl C, et al. Endoscopic and surgical treatments for achalasia: a systematic review and metaanalysis. Ann Surg 2009;249:45–57. 12. Richards WO, Torquati A, Holzman MD, et al. Heller myot-
omy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg 2004;240:405–412. Harris JA, Gallo CD, Brummett DM, et al. Extra-abdominal pneumodissection after laparoscopic antireflux surgery. Am Surg 2001;67:885–889. Morino M, Rebecchi F, Festa V, Garrone C. Preoperative pneumatic dilatation represents a risk factor for laparoscopic Heller myotomy. Surg Endosc 1997;11:359–361. Beckingham IJ, Callanan M, Louw JA, Bornman PC. Laparoscopic cardiomyotomy for achalasia after failed balloon dilatation. Surg Endosc 1999;13:493–496. Horgan S, Hudda K, Eubanks T, et al. Does botulinum toxin injection make esophagomyotomy a more difficult operation? Surg Endosc 1999;13:576–579. Patti MG, Feo CV, Arcerito M, et al. Effects of previous treatment on results of laparoscopic Heller myotomy for achalasia. Dig Dis Sci 1999;44:2270–2276. Snyder CW, Burton RC, Brown LE, et al. Multiple preoperative endoscopic interventions are associated with worse outcomes after laparoscopic Heller myotomy for achalasia. J Gastrointest Surg 2009;13:2095–2103. Cowgill SM, Villadolid DV, Al-Saadi S, Rosemurgy AS. Difficult myotomy is not determined by preoperative therapy and does not impact outcome. JSLS 2007;11:336–343. Stavropoulos SN, Harris MD, Hida S, et al. Endoscopic submucosal myotomy for the treatment of achalasia (with video). Gastrointest Endosc 2010;72:1309–1311. Perretta S, Dallemagne B, Donatelli G, et al. Transoral endoscopic esophageal myotomy based on esophageal function testing in a survival porcine model. Gastrointest Endosc 2011;73: 111–116.
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REFERENCES
13. 14. 15. 16. 17. 18.
19. 20. 21.
esophageal junction (GEJ). Although this surgical intervention is now performed primarily by minimally invasive techniques,2,3 dissection of the LES still requires several abdominal incisions and some sort of surgical antireflux procedure, which is accompanied by a certain morbidity rate. A potentially less invasive endoscopic method for division of the LES, using a needle-knife to cut the esophageal muscle from the lumenal side, was described by Ortega and colleagues4 in 1980. Due to concerns about mediastinal contamination or the lack of physical separation of the muscle edges, this method has not been further pursued. More than 25 years later, intellectual efforts to push the boundaries of flexible endoscopy and natural orifice translumenal endoscopic surgery (NOTES) led to the development of a novel treatment modality for achalasia. Pasricha and colleagues5 initially described the feasibility of an endoscopic submucosal esophageal myotomy in a survival animal model. Others have demonstrated this technique together with endolumenal antireflux procedures in survival animals.6 The first report in humans was from Inoue
Esophageal achalasia is a motility disorder involving failure of the lower esophageal sphincter (LES) to relax in response to swallowing and aperistalsis of the esophageal body. There is no known underlying cause,1 although autoimmune reactions against the myenteric nerve plexi have been postulated. Therapy focuses on the forced relaxation of the LES by endoscopic or surgical means. Noninvasive procedures are primarily botulinum toxin injection or esophageal dilatation. Because only few randomized controlled trials have tried to define the optimal strategy, treatment still varies widely. Surgical esophagomyotomy very effectively disrupts the esophageal muscular layers at the gastroDisclosure information: Nothing to disclose. Received July 12, 2011; Revised September 8, 2011; Accepted September 8, 2011. From The Oregon Clinic, Division of GI and Minimally Invasive Surgery (Swanström, Dunst) and Legacy Health System (Rieder), Portland, OR. Correspondence address: Lee L Swanström, MD, FACS, Division of GI and Minimally Invasive Surgery, The Oregon Clinic, 1040 NW 22nd Ave, Suite 560, Portland, OR 97210. email: [email protected]
© 2011 by the American College of Surgeons Published by Elsevier Inc.
751
ISSN 1072-7515/11/$36.00 doi:10.1016/j.jamcollsurg.2011.09.001
752
Swanström et al
Peroral Endoscopic Myotomy
J Am Coll Surg
Step 1 Abbreviations and Acronyms
EGD GEJ LES NOTES POEM
⫽ ⫽ ⫽ ⫽ ⫽
esophagogastroduodenoscopy gastroesophageal junction lower esophageal sphincter natural orifice translumenal endoscopic surgery peroral endoscopic myotomy
and colleagues,7 who coined the term POEM (peroral endoscopic myotomy) and reported on favorable results in 17 achalasia patients. Based on the procedure described by Inoue and our own animal studies,8 we initiated a clinical study in October 2010 and describe the technical steps of and early outcomes of POEM as a less invasive treatment option for treatment of refractory achalasia and other esophageal motility disorders.
METHODS The IRB of the Legacy Health System, Portland, OR, approved an initial 5 patients to be included in a prospective clinical study evaluating the described POEM procedure for esophageal motility disorders requiring myotomy (trial number: NCT01302288, http://www.clinicaltrials.gov). Inclusion criteria for this trial were eligibility for elective Heller myotomy and age greater than 18 years. Exclusion criteria were previous esophageal or mediastinal surgery or a body mass index greater than 40 kg/m2. Previous interventions such as dilatation or botulinum toxin injection were not considered contraindications because they were no longer contraindicated for laparoscopic approaches. However, patients with massively dilated or sigmoid esophagus were not included in this initial series. All patients had physiology testing performed before surgery, including manometry, esophagogastroduodenoscopy (EGD), and timed barium swallow. A standardized validated symptom assessment form was administered to the patient before surgery at each subsequent visit;9 this tool includes a dysphagia score graded on a Lickert scale with grade 0 (absent), grade 1 or 2 (moderate), and grade 3 or 4 (severe). Endoscopic technique
Patients were placed on a clear liquid diet for 24 hours and given a single preoperative dose of a first generation cephalosporin. With the patient under general anesthesia and in the supine position, EGD was performed using a highresolution upper endoscope (GIF-H180J, Olympus) and carbon dioxide (CO2) insufflation (3 L/min). After preliminary surveillance, an overtube was placed and an angled dissection cap was mounted onto the endoscope to facilitate the submucosal view. Our stepwise approach to perform POEM is outlined below.
A site for mucosotomy that is approximately 7 to 10 cm proximal to the GEJ is identified. A submucosal “lift” is performed by injecting the right anterior lumenal side of the esophagus with 3 mL of saline mixed with epinephrine and methylene blue. The elevated mucosa is then incised longitudinally for 1.5 to 2 cm using a needle-knife cautery to enable submucosal insertion of the flexible endoscope (Fig. 1A). Step 2
The endoscope is then inserted into the submucosal space and an endoscopic tunnel is created. A combination of blunt dissection with the cap and careful electrocautery with a triangle-shaped tip needle-knife (TT-knife, Olympus) as shown in Figure 1B is used. CO2 insufflation and saline infusion facilitates the dissection. Hot biopsy forceps were used to coagulate larger submucosal vessels before dissection. The submucosal tunnel is created along the lesser curvature and extended below the LES onto the gastric cardia. A retroflexed view is used to ensure an adequate extension onto the stomach. Step 3
Dissection of only the inner circular muscle layer and sling fibers of the LES is carried out starting approximately 4 cm above the LES and extending 2 to 3 cm onto the gastric cardia. A special triangle-tip knife, designed for endoscopic submucosal dissection, was used with monopolar coagulation. A spray current of maximum 40 watts is used for the myotomy by lifting and dividing the muscle fibers, as demonstrated in Figure 1C. Radial tension from both the dissecting cap and the CO2 insufflation further facilitates division of the circular muscle fibers. When an appropriate myotomy is achieved, the flexible endoscope is withdrawn and smooth passage through the GEJ is evaluated. Step 4
After withdrawing the endoscope from the submucosal tunnel, the mucosal incision is closed by standard endoscopic hemoclips (Fig. 1D). Each patient had a postoperative gastrografin esophagogram on the first postoperative day and was started on a pureed diet, which was continued for 1 week after discharge. The initial clinical follow-up was arranged at 2 weeks.
RESULTS Patients
The 5 patients (2 women/3 men) had a median age of 67 years (range 49 to 78 years) and a median body mass index of 25.0 kg/m2 (range 23.7 to 27.1 kg/m2). Four of the 5 patients were previously diagnosed with achalasia, 3 of whom had hypertensive LES pressures (resting pressure of 55.1 mmHg (range 37.2 to 58.8 mmHg) and a median residual LES pressure of
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Figure 1. (A) Endoscopic view of the elevated mucosa, which is incised by needle-knife cautery to enable submucosal insertion of the flexible upper endoscope (dissection cap attached). (B) In the submucosal space an endoscopic tunnel is created mainly by careful electrocautery with a triangle-shaped tip needle-knife. Note the muscular layer visible on the left and the esophageal mucosa on the right of the endoscopic image (dissection cap attached). (C) Only the inner esophageal muscle fibers (*) are divided, using the triangle-shaped tip needle-knife (***). The intact outer longitudinal muscle layer (**) can be visualized (dissection cap attached to the endoscope). (D) The mucosal incision is closed by standard endoscopic clips. Note the remaining opening of the mucosa before complete closure.
36.5 mmHg (range 9.9 to 39.8 mmHg). Recent manometry data were not available for 1 patient, who had a more than 10-year history of achalasia and old motility reports confirming no motility and who had been treated several times with botulinum toxin injections and dilatations since his original diagnosis. Three other patients had previous botulinum toxin injections as well. One of the 5 patients was initially diagnosed as having achalasia, but on further studies in our laboratory was actually found to
have 30% peristalsis with distal esophageal spasm (distal esophageal contraction mean amplitude of 233 mmHg). A normal LES resting pressure with incomplete relaxation (16.8 mmHg) therefore led to the more accurate diagnosis of nutcracker esophagus with an incompletely relaxing LES. Endoscopic procedure
The initial mucosal incision was carried out at 9.2 cm (range 8 to 11 cm) above the GEJ and the subsequently
754
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Peroral Endoscopic Myotomy
J Am Coll Surg
Figure 2. The extension of the myotomy onto the stomach (3 cm) can be visualized and measured in retroflex endoscopic view.
created submucosal tunnel onto the lesser curvature had a median length of 10 cm (range 10 to 13 cm). The submucosal tunnel was dissected primarily by electrocautery using the triangle tip-shaped needle knife. Myotomy of the inner circular esophageal muscle fibers was achieved in all (5 of 5) cases, with a median length of 7.5 cm (range 6 to 12 cm). The longest myotomy was for the diffuse esophageal spasm/nutcracker patient. It was extended into the gastric cardia for 2 cm (range 1 to 3 cm). In 2 cases there was a small mucosal perforation in the gastric cardia. It did not interfere with the procedure and closure was made with standard endoscopic clips after the myotomy. There was no obvious breach of the longitudinal muscle layer, but this layer was observed to be very thin. Three patients (3 of 5) developed CO2 pneumoperitoneum diagnosed by clinical palpation of the abdominal wall. No patient was noted to have capnomediastinum. A Veress needle placed in the left upper quadrant under sterile conditions normalized the abdominal pressure in all 3 patients. After the myotomy but before mucosal closure, the endoscope was withdrawn from the submucosal tunnel and advanced through the GEJ. Smooth passage of the endoscope into the stomach was observed immediately after myotomy in all patients. The mucosal incision was successfully closed in all patients using an average of 7 clips. Retroflexion showed adequate extension of the dissection onto the gastric cardia in all cases (Fig. 2). Procedure time ranged from 120 to 240 minutes. Intraoperatively, the blood pressure, heart rate, and ventilation parameters remained in the normal range for the duration of the procedure. Early postoperative results
Water-soluble upper gastrointestinal x-rays were obtained on postoperative day 1 in all cases. There was no esophageal
Figure 3. Transnasal endoscopy at the initial 2-week postoperative follow-up shows a perfectly healed mucosa with the clips still in place.
leakage and there was free flow into the stomach in all cases. Patients were discharged on postoperative day 1 (mean length of stay was 1.2 ⫾ 0.4 days) by protocol and no clinical complications in the perioperative period were observed. At the 2-week clinical follow-up, all patients reported immediate symptom relief (dysphagia score of 0 or 1) and no need for postoperative pain medication. One patient agreed to have unsedated transnasal endoscopy at the first follow-up to assess the status of the esophageal closure. A perfectly healed esophageal mucosa was observed with the hemoclips still in place (Fig. 3).
DISCUSSION Shortly after the experimental animal studies of Pasricha and colleagues5 describing endoscopic methods of esophageal myotomy were reported, the surgeon H Inoue and associates demonstrated that this noninvasive technique was also applicable to humans with achalasia7 and other spastic esophageal motility disorders.10 Since October 2010 we have been performing peroral endoscopic myotomies in patients diagnosed with profound esophageal motility disorders under an IRB-approved trial. Our initial experience has shown that this is a safe and extremely effective therapy and that it deserves consideration as a primary treatment for the disease. All current treatments for esophageal achalasia have different advantages and draw-
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backs, so the ideal approach is still debated. Endoscopic balloon dilatation is still widely performed because of its relative noninvasiveness, but it has a lower success rate and often requires multiple treatments.11 It can also result in a substantial perforation rate. Laparoscopic myotomy is long established and is probably more definitive, but it is an invasive surgical procedure, which involves complete mobilization of the GEJ with subsequent requirement of an antireflux operation.12 The appeal of the POEM procedure is that it specifically targets, and allows surgical division of, only the muscle layers of the LES affected by achalasia, thereby preserving the anatomic integrity of the LES anatomy and possibly minimizing postoperative reflux. More than nearly 50% of laparoscopic Heller myotomy patients without a fundoplication will have pathologic reflux, and even as many as 10% of patients with a Heller and partial fundoplication will have problems,12 but early reports of the POEM procedure potentially indicate a lower incidence. Current data, including ours, clearly indicate the safety of the procedure. The only clinical relevant adverse event observed in our series was development of a pneumoperitoneum in 3 patients, resolved with placement of a Veress needle to decompress it. There were no postoperative consequences of this intervention. Inoue described this occurrence as well in 10% of his most recent series of more than 100 patients (personal communication) and theorized that it might occur due to gas permeation through the remarkably thin longitudinal muscle fibers of the esophagus. No pneumomediastinum was noted in our series. This, however, would usually not be considered a complication because during laparoscopic dissection at the hiatus, as it has a reported incidence as high as 85% but resolves within few days.13 A concern of this new approach is whether previous interventions (balloon dilatations or botulinum toxin injections) would be contraindicated due to a possibly higher incidence of complications.14-18 However, other authors have noticed no such problems.19 One patient in our clinical series had several balloon dilatations before surgery, and 3 patients had previous botulinum toxin therapy. We did not note any particular difficulty with these previously treated patients but our numbers are of course low. We tried to make all myotomies on the right anterior esophageal side along the lesser curvature. This approach was previously observed to be easier compared with a posterior myotomy.7 Others theorized the potential benefit of a posterior approach because a later anterior surgical myotomy could still be performed if recurrent symptoms occurred.20 All patients in our early series reported immediate symptom relief without the need for postoperative pain medication. Additionally, a postoperative transnasal EGD
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performed in one patient observed a perfectly healed mucosa at the 2-week follow-up. However, whether POEM is as effective as the current surgical “gold standard” has to be evaluated by further objective testing. Inoue and coworkers7 reported a 70% drop in the LES pressure in patients with nonsigmoid esophagi, and 50% drop in patients with sigmoid esophagi. A recent experimental study evaluating the postoperative decrease of the LES pressure found the endoscopic submucosal approach less effective than open myotomy.21 On the other hand, measurement of the GEJ distensibility found similar results in both groups. However, because this was a physiologic, nonachalasic model, comparisons to the clinical setting may not be valid. Weaknesses of our study include the small numbers and current lack of long-term follow-up. We will continue to accrue data prospectively and are in the process of obtaining comprehensive physiology studies at 6 months, including upper endoscopy, timed barium swallow, impedence/pH testing, and motility, as well as long-term (3-year) follow-up. We believe that the surgical community needs to be aware of this new and potentially better approach to achalasia as soon as possible so it can prepare training opportunities and prospective outcomes studies.
CONCLUSIONS We describe our initial clinical experience with 5 patients treated with POEM for esophageal dismotility disorders and report excellent outcomes and feasibility. These early results add more data on the safety and feasibility of this approach to the current literature. All our patients had immediate subjective symptom relief and no infectious complications. Notably, there was no pain related to the procedure, which also took no longer than a typical laparoscopic treatment. This seems to validate the initial promise of NOTES and, if long-term results are favorable, this may be the first NOTES procedure to achieve a “gold standard” status. Author Contributions
Study conception and design: Swanström, Rieder, Dunst Acquisition of data: Swanström, Rieder, Dunst Analysis and interpretation of data: Swanström, Rieder, Dunst Drafting of manuscript: Swanström, Rieder Critical revision: Swanström, Rieder, Dunst Acknowledgement: The authors thank Olympus, USA, for providing the high-resolution upper endoscope and endoscopic instrumentation.
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1. Gockel HR, Schumacher J, Gockel I, et al. Achalasia: will genetic studies provide insights? Hum Genet 2010;128:353–364. 2. Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology 2010;139:369–374. 3. Patti MG, Fisichella PM, Perretta S, et al. Impact of minimally invasive surgery on the treatment of esophageal achalasia: a decade of change. J Am Coll Surg 2003;196:698–703. 4. Ortega JA, Madureri V, Perez L. Endoscopic myotomy in the treatment of achalasia. Gastrointest Endosc 1980;26:8–10. 5. Pasricha PJ, Hawari R, Ahmed I, et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy 2007;39:761–764. 6. Perretta S, Dallemagne B, Allemann P, Marescaux J. Multimedia manuscript. Heller myotomy and intraluminal fundoplication: a NOTES technique. Surg Endosc 2010;24:2903. 7. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42:265–271. 8. Spaun GO, Dunst CM, Arnold BN, et al. Transcervical Heller myotomy using flexible endoscopy. J Gastrointest Surg 2010;14: 1902–1909. 9. Khajanchee YS, Kanneganti S, Leatherwood AE, et al. Laparoscopic Heller myotomy with Toupet fundoplication: outcomes predictors in 121 consecutive patients. Arch Surg 2005;140: 827–833. 10. Chiu PWY, Inoue H, Teoh AYB, et al. Per-oral endoscopic myotomy for treatment of hypertensive lower esophageal sphincter. Gastrointest Endosc 2011;73:AB 107. 11. Campos GM, Vittinghoff E, Rabl C, et al. Endoscopic and surgical treatments for achalasia: a systematic review and metaanalysis. Ann Surg 2009;249:45–57. 12. Richards WO, Torquati A, Holzman MD, et al. Heller myot-
omy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg 2004;240:405–412. Harris JA, Gallo CD, Brummett DM, et al. Extra-abdominal pneumodissection after laparoscopic antireflux surgery. Am Surg 2001;67:885–889. Morino M, Rebecchi F, Festa V, Garrone C. Preoperative pneumatic dilatation represents a risk factor for laparoscopic Heller myotomy. Surg Endosc 1997;11:359–361. Beckingham IJ, Callanan M, Louw JA, Bornman PC. Laparoscopic cardiomyotomy for achalasia after failed balloon dilatation. Surg Endosc 1999;13:493–496. Horgan S, Hudda K, Eubanks T, et al. Does botulinum toxin injection make esophagomyotomy a more difficult operation? Surg Endosc 1999;13:576–579. Patti MG, Feo CV, Arcerito M, et al. Effects of previous treatment on results of laparoscopic Heller myotomy for achalasia. Dig Dis Sci 1999;44:2270–2276. Snyder CW, Burton RC, Brown LE, et al. Multiple preoperative endoscopic interventions are associated with worse outcomes after laparoscopic Heller myotomy for achalasia. J Gastrointest Surg 2009;13:2095–2103. Cowgill SM, Villadolid DV, Al-Saadi S, Rosemurgy AS. Difficult myotomy is not determined by preoperative therapy and does not impact outcome. JSLS 2007;11:336–343. Stavropoulos SN, Harris MD, Hida S, et al. Endoscopic submucosal myotomy for the treatment of achalasia (with video). Gastrointest Endosc 2010;72:1309–1311. Perretta S, Dallemagne B, Donatelli G, et al. Transoral endoscopic esophageal myotomy based on esophageal function testing in a survival porcine model. Gastrointest Endosc 2011;73: 111–116.
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