Curr Gastroenterol Rep (2014) 16:369 DOI 10.1007/s11894-013-0369-6
ESOPHAGUS (L GERSON, SECTION EDITOR)
Per-Oral Endoscopic Myotomy (POEM) for Esophageal Achalasia Radu Pescarus & Eran Shlomovitz & Lee L. Swanstrom
Published online: 22 December 2013 # Springer Science+Business Media New York 2013
Abstract Per-oral endoscopic myotomy (POEM) is a new minimally invasive endoscopic treatment for achalasia. Since the first modern human cases were published in 2008, around 2,000 cases have been performed worldwide. This technique requires advanced endoscopic skills and a learning curve of at least 20 cases. POEM is highly successful with over 90 % improvement in dysphagia while offering patients the advantage of a low impact endoscopic access. The main long-term complication is gastroesophageal reflux (GER) with an estimated incidence of 35 %, similar to the incidence of GER post-laparoscopic Heller with fundoplication. Although POEM represents a paradigm shift in the treatment of achalasia, more long-term data are clearly needed to further define its role in the treatment algorithm of this rare disease. Keywords Therapeutical endoscopy . Endoscopic . Achalasia . POEM . Myotomy . Dysphagia
Introduction Achalasia was first described by Sir Thomas Willis in 1674 as a failure of esophageal relaxation (from the Greek chalasis or relaxation) [1]. It is now understood that a loss of inhibitory innervation of the lower esophageal sphincter (LES) results in inadequate relaxation and higher baseline pressures of the LES. Additionally, achalasia also features an absence of esophageal peristalsis. This chronic disease represents the
This article is part of the Topical Collection on Esophagus R. Pescarus : E. Shlomovitz : L. L. Swanstrom (*) Providence Cancer Center, Division of Gastrointestinal and Minimally Invasive Surgery, The Oregon Clinic, Portland, OR, USA e-mail: [email protected]
most common primary motility disorder of the esophagus with various clinical features including regurgitation, dysphagia, retrosternal pain, and weight loss. Despite being a well-known pathology to the foregut surgeon, achalasia remains a rare disease with an annual incidence of approximately 1/100,000 per year [2]. Although the exact etiology of achalasia remains unknown, the most widely accepted theory is that it is caused by an autoimmune attack on the myenteric plexus of the esophagus in individuals with a genetic predisposition [2]. Although no cure has been identified, numerous palliative treatments including medical, endoscopic, and surgical have been proposed, all directed at lowering LES pressure. Medical treatment with nitrate and calcium antagonists is limited due to their poor efficacy and significant side effects [3•, 4, 5•]. However, these smooth muscle relaxants may be helpful in relieving some of the chest pain in patients with vigorous achalasia. Endoscopic treatments have traditionally included Botox injections and pneumatic dilatation (PD). Botox injections at the gastresophageal junction (GEJ) are initially successful in over 90 % of patients; however, the effects last only 6–9 months in the average patient. Botox injections are therefore generally reserved for elderly patients or poor surgical candidates [6]. Pneumatic dilatation is arguably the nonsurgical technique with the highest success rate [7]. A recent multicenter randomized study seemed to demonstrate equivalent clinical success of PD and laparoscopic Heller myotomy (LHM) with Dor fundoplication at 2-year follow-up [8]. In the long-term, however, the failure rate of PD has been shown to be in the region of 50–60 % making LHM the treatment of choice in young or otherwise healthy patients [7]. A new endoscopic technique—the per-oral endoscopic myotomy (POEM) that combines the surgical element of a controlled myotomy with the low impact of endoscopic access—has been establishing itself as a valid alternative in the treatment algorithm of achalasia [9].
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Historical Background of POEM The first reported endoscopic myotomy performed in 17 achalasia patients was published by Ortega in 1980 [10•]. This was a division of both the mucosa and muscle of the LES, which obviously has an element of risk as it exposes the wound directly to gastric contents and, if too deep, would become a direct hole into the peritoneum or mediastinum. The clinical, manometric ,and radiological post-operative results of all 17 patients were, however, satisfactory with only 3 minor bleeding episodes, which were controlled endoscopically. The medical community, however, did not initially adopt this new technique as it was thought to have too high a potential for complications. It was not until 2007 that Parischa and his team re-invented the procedure and demonstrated its feasibility in four pigs [11]. They improved the safety aspect by creating a mucosal flap to access the muscle. A unique aspect of the procedure they described is the division of only the circular muscle of the esophagus and LES, making this a potentially more “targeted” treatment. The first modern series of patients that underwent POEM for achalasia was described shortly thereafter in 2008 by Dr Inoue and his team [12•]. Currently, around 2,000 cases have been performed worldwide with growing enthusiasm surrounding this endoscopic procedure.
Patient Selection and Operative Indication It is generally recommended that teams beginning a POEM program should do it with institutional review board approval. Our initial exclusion criteria were age under 18 years, inability to undergo general anesthesia, previous esophageal or mediastinal surgery (excluding botox injections and pneumatic dilatations), and a BMI over 40 [13•]. A previous Heller myotomy is no longer considered a contraindication [3•, 14]. Additionally, patients as young as 3 years old have been reported as well as very elderly. Currently, the inability to undergo general anesthesia seems to be the only valid contraindication once the obligatory learning curve has been completed. Although it is thought that patients with achalasia benefit most from POEM, other esophageal pathologies such as diffuse esophageal spasm (DES), non-relaxing hypertensive LES, and Nutcracker esophagus may be palliated by an endoscopic myotomy [9, 15•].
Pre-Operative and Post-Operative Investigations All patients should undergo extensive pre-operative investigations including high-resolution manometry, esophagogastroscopy, and barium swallow study. For outcomes reasons, we repeat these tests 6-months postoperatively. In addition, a 24-h pH study should be obtained
Curr Gastroenterol Rep (2014) 16:369
as iatrogenic gastroesophageal reflux is a possibility and is asymptomatic 50 % of the time. A standardized validated symptom assessment form is completed by all patients. Preoperatively, all patients are put on clear liquid diet for 1 day before the procedure. Patients are treated with oral Nystatin for 5 days pre-operatively to preemptively treat any potential esophageal Candida overgrowth. They receive one prophylactic dose of antibiotics as well as a dose of Dexamethasone at the start of the procedure to minimize mucosal edema, which can make closure of the mucosa more difficult. A contrast upper GI study is performed on post-operative day 1 to rule out any immediate complications. Bloodwork is not routinely necessary after the intervention. The average length of stay is 24 h.
Technical Aspects of POEM Procedure Set-Up and Positioning The procedure is done in the operating room under general anesthesia with endotracheal intubation. CO2 insufflation is used to reduce the risk of air embolism, pneumothorax and subcutaneous emphysema. A high-resolution endoscope, an overtube for stabilization of the endoscope, dissecting cap, injection needle, triangle or hook tip knife, coagulation forceps, and endoscopic clips are essential. Access to an endoscopic suturing device is also extremely helpful in cases of iatrogenic perforations, and can also be used to close the mucosotomy. A thorough cleaning of the esophageal lumen is done before the beginning of the intervention. Sterile saline should be used during the creation of the submucosal channel given the potential mediastinal or peritoneal entry. Communication with the anesthesia team is essential as the patient may develop a tension pneumoperitoneum during the procedure in up to 10 % of the cases. If ventilation pressures increase and tidal volumes decrease significantly, the patient may require a Veres needle decompression of the pneumoperitoneum. Mucosal Entry Initially, the distal end of the dissection 2 cm distal from the GEJ on the lesser curvature is marked with methylene blue upon retroflexion in the stomach (Fig. 1a). A mucosal lift is then performed with saline injection containing a small amount of methylene blue on the right anterior side of the esophageal wall (Fig. 1b). This is followed by a longitudinal 1-to 2-cm mucosotomy. Its orientation is important as transverse incisions are nearly impossible to close with clips. Once the submucosal space is entered, a 12-mm biliary stone extraction balloon is inflated so as to ensure adequate opening of the mucosa and facilitate the introduction of the scope into the
Curr Gastroenterol Rep (2014) 16:369
Page 3 of 7, 369
Fig. 1 Key steps of the POEM procedure. a) Marking the distal end of the dissection 2 cm distal from the GEJ on the short curvature. b) Creation of the submucosal lift. c) Opening of the submucosal channel using sharp dissection. d) Injection of lifting solution through the balloon allows correct delineation of the submucosal plane. e) Sharp dissection of the circular muscle fibers. f) Intraoperative retroflexed view confirming 2 cm extension of myotomy onto stomach wall. g) Multiple clip closure of the mucosal defect
submucosal plane. The next steps are facilitated by the presence of a dissection cap placed on the tip of the scope. A fenestrated cap is preferred as it prevents tissue from being sucked into the cap, which impedes visualization during the procedure. Creation of a Submucosal Tunnel Each step of the procedure requires endoscopic expertise and familiarity with the extra-lumenal anatomy of the
esophagus and proximal stomach, particularly the tunnel creation. It is vital that the submucosal tunnel extends beyond the GEJ for about 2 cm onto the proximal stomach. This submucosal tunnel is created using a combination of spray coagulation, C02 insufflation, and blunt dissection (Fig. 1c). Repeated injections of lifting solution (saline, diluted methylene blue, and epinephrine) through the balloon enables better delineation of the submucosal plane, separates the mucosa and muscle, and acts as a protective heat sink to protect the mucosa (Fig. 1d).
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Curr Gastroenterol Rep (2014) 16:369
Identification of GEJ Correct identification of the GEJ is crucial if one wants to obtain an adequate myotomy on the gastric side of at least 2 cm. Various endoscopic findings such as the length of insertion of the endoscope, the presence of palisading mucosal vessels, and the transitory increase and later decrease in the resistance of dissection when passing the LES. One can also identify the relatively increased thickness of the circular muscle bundles of the lower esophageal sphincter, followed by the yellowish characteristic appearance of the submucosal cardial space that also harbors an increased number of vessels. Finally, the discoloration of the cardial mucosa overlying the submucosal tunnel as seen upon retroflexion of the scope in the lumen of the stomach allows for an estimate of the distance from the GEJ (Fig. 1f). Circular Muscle Myotomy The selective myotomy of the circular bundles starts 2 cm distal to the mucosal entry site. Careful use of the triangle tip knife or other spray coagulation devices is paramount as both the mucosa on one side and the longitudinal muscle layer on the other side should be preserved (Fig. 1e). Inoue et al. originally described a 10-cm myotomy on the esophageal side and 2-cm below the GEJ [12•]. The extent of the myotomy can be modified by the interpretation of the endoscopic images and by the pre-operative manometry results (Fig. 2a, b). Given the high incidence of GER post-POEM, our team and others have attempted to decrease the length of the myotomy, except for cases of vigorous achalasia where a longer myotomy is warranted. This tailored approach is facilitated by a new endoluminal functional lumen-imaging probe (EndoFLIP; Crospon, Galway, Ireland) that measures the GEJ distensibility before and after the selective myotomy [16•] (Fig. 2c). Closure of the Mucosotomy The mucosal entry site is closed with endoscopic clips at the end of the procedure (Fig. 1g). Usually 1.5–2 cm in length, the opening is closed with several clips starting at the distal end ensuring complete closure of the defect. A few alternative closure methods have been described in situations where the usual endoscopic clips fail. Both over-the-scope clips (OTSC) [17] as well as fibrin sealants in the case of perforation of the gastric cardia [18] have been described. Another option for mucosotomies that cannot be closed is a covered stent [19]. Finally, an endoluminal suturing device (OverStitch; Apollo Endosurgery, Austin, TX, USA) was first employed for a twolayered closure of an inadvertent full-thickness esophagotomy during a POEM procedure [20]. It is advisable that this endoscopic suturing device is available for POEM cases as it represents a good alternative to clips in difficult situations.
Fig. 2 a) Comparison between pre and post-POEM high-resolution manometry findings in Chicago Type I achalasia. b) Comparison between pre and post-POEM high-resolution manometry findings in Chicago Type II achalasia. c) Example of intra-operative EndoFlip use before and after a POEM procedure
Post-Operative Care The morning of post-operative day 1, all patients undergo an upper GI contrast study to rule out a mucosal defect and to
Curr Gastroenterol Rep (2014) 16:369
ensure adequate opening of the GEJ post myotomy. If clinically well and free of radiological evidence of complications, the patients are discharged on post-operative day 1 with instructions to follow a liquid and pureed diet for 1 week. At 6-months post-intervention, the patient is re-scheduled for follow-up manometry, pH study, and esophagogastroscopy. In the long term, we recommend an upper endoscopy to be done every 5 years in all achalasia patients, given the slightly increased risk for esophageal carcinoma [21].
Complications Short-Term Complications Obviously, the most feared complication would be a postoperative mediastinal leak. Fortunately, the 2 layers of protection (preserved longitudinal muscle and intact mucosa) make this complication rare in all published series. Perforation of the longitudinal muscular layer with complete communication with the mediastinum or abdominal cavity happens relatively frequently due to the tenuous nature of the longitudinal muscle layer. It is also not repairable endoscopically, and therefore is ignored when it happens. On the other hand, if there are mucosal perforations they should be carefully closed. A clinically significant pneumoperitoneum or pneumothorax manifested by difficult ventilation may require decompression with a Veres needle or chest drain. Rarely, excessive hypercarbia resulting from the extended CO2 administration may delay the post-operative extubation especially in medically marginal patients. An incomplete closure of the mucosotomy is usually diagnosed on the upper GI study done postoperatively. This is an indication for endoscopic evaluation and repair by the addition of clips. Any mucosal perforation elsewhere along the myotomy has to be followed by careful closure. Long-Term Complications One of the most common long-term complications seen with this procedure is gastroesophageal reflux (GER). In our initial experience, 46 % of patients demonstrated an abnormal pH study post-operatively and overall 50 % of the cohort had either pH or endoscopic evidence of reflux [13•]. Similarly, a rate of up to 60 % endoscopic evidence of reflux (pH study was not performed) was published by a European team [22]. Our more recent experience has shown an objective incidence of around 35 %, possible due to tailoring our myotomy length based on Endoflip measurements. This is comparable to laparoscopic Heller with fundoplication [13•].
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Results More than 2,000 cases of POEM have been performed worldwide. There are at least 16 centers performing POEM with more than 25 different operators [15•]. Children as young as 3 years and elderly patients up to 97 years of age have undergone the POEM procedure. The mean duration of the case is between 90 and 120 min and varies with the experience of the operator [15•]. POEM after prior endoscopic treatment (Botox or balloon dilation) is safe as demonstrated by the absence of statistical difference between the length of the procedure or the incidence of complications [23•]. POEM after previous Heller myotomy has been performed in a few centers and seems to be associated with increased difficulty and increased complication rate, but no difference in clinical results [15•]. Intermediate-term clinical success at an average of 9.3 months after POEM is high, with dysphagia relief ranging from 90 to 100 % and an average of 98 % [15•]. GER symptoms are present in 0–44 % of patients, with a reported anti-acid use of 0–50 % post-POEM. Endoscopic evidence of erosive esophagitis is present in 0–43 % and positive pH studies were present in 0–38 % of patients. Although these numbers reflect a high incidence of post-operative GER, they are in fact similar to the 21–42 % of abnormal pH studies postlaparoscopic Heller and partial fundoplication [24]. When no complications arise, the patients leave the hospital in the morning of the first post-operative day. Usually no pain medications are necessary. Patients return to work an average of 3 days after the intervention.
Learning Curve in Performing POEM The POEM procedure requires a unique set of skills. While having advanced endoscopic skills is a sine qua non, the team performing the procedure must be familiar with the gastroesophageal junction and the physiopathology of achalasia, as well as having a well-defined algorithm when dealing with the most frequent complications. A learning curve of approximately 20 cases has been proposed for an experienced endoscopist [25]. Indeed, the length of the procedure and the incidence of inadvertent mucosotomies seem to plateau after 20 cases [25]. This is similar to the learning curve postlaparoscopic Heller myotomy as described by Bloomston in 2002 [26]. Training in the laboratory may facilitate the acquisition of the skills necessary to perform the POEM procedure. The pig explant model containing the esophagus and stomach represents a good inanimate model. Once the training on the explant model is completed, one should further perfect the technique using a live porcine model. Cadaver models are also
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a possibility with the advantage of a more realistic anatomy. Finally, a large part of the skill set necessary to perform endoscopic submucosal dissections (ESD) is also necessary for POEM. Mastering ESD may be an obligatory step before becoming a POEM expert [9].
Future Directions
Curr Gastroenterol Rep (2014) 16:369
References Papers of particular interest, published recently, have been highlighted as: • Of importance
1. 2.
One of the most important long-term complications of the POEM procedure, the iatrogenic GER, needs to be better studied. Objective endoscopic and pH measurements are necessary along with longer post-operative follow-up. Technical modifications such as tailoring the length of the myotomy based on intra-operative electrophysiological measurements will hopefully reduce the incidence of this problem. Longerterm follow-up will further define whether their post-operative symptoms will be adequately controlled medically. In the future, multi-center prospective randomized studies comparing laparoscopic Heller myotomy and POEM, as well as POEM versus balloon dilation, would further define the unique role of POEM in the treatment algorithm of this rare disease. Equally important will be to define the therapeutic success of POEM in the other non-achalasia esophageal motility disorders.
3.•
4. 5.•
6. 7.
8.
9. 10.•
Conclusion 11.
The POEM procedure represents a clear paradigm shift in the treatment of achalasia and is arguably among the most successful natural orifice translumenal endoscopic surgery (NOTES) procedures. Through its minimally invasive character, it offers excellent palliation in achalasia patients with good clinical results and low adverse events. This endoscopic myotomy procedure requires excellent endoscopic skills and a definite learning curve of at least 20 cases. This will undoubtedly limit its adoption to high-volume esophageal centers. Further studies are needed with greater numbers of patients and longer follow up. Equally important will be to perfect the inanimate and animal models to create adequate training environments for the future POEM providers. Compliance with Ethics Guidelines Conflict of Interest Dr. Shlomovitz declares no conflicts of interest. Dr. Swanstrom has served as a consultant for Olympus and received a grant from Boston Scientific. Dr. Pescarus has no conflicts of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by the author.
12.•
13.•
14.
15.•
16.•
17.
18.
Cash BD, Wong RK. Historical perspective of achalasia. Gastrointest Endosc Clin N Am. 2001;11(2):221–34. v. Gockel HR et al. Achalasia: will genetic studies provide insights? Hum Genet. 2010;128(4):353–64. Eleftheriadis N et al. Training in peroral endoscopic myotomy (POEM) for esophageal achalasia. Ther Clin Risk Manag. 2012;8: 329–42. Good comprehensive review about POEM from a practical perspective. Beck WC, Sharp KW. Achalasia. Surg Clin North Am. 2011;91(5): 1031–7. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol. 2013. Most recent American College of Gastrenterology guidelines for the treatment of achalasia. Chuah SK et al. 2011 update on esophageal achalasia. World J Gastroenterol. 2012;18(14):1573–8. Allaix ME, Patti MG. What is the best primary therapy for achalasia: medical or surgical treatment? Who owns achalasia?. J Gastrointest Surg. 2013. Boeckxstaens GE et al. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med. 2011;364(19):1807–16. Swanstrom LL. Peroral endoscopic myotomy for treatment of achalasia. Gastroenterol Hepatol (N Y). 2012;8(9):613–5. Ortega JA, Madureri V, Perez L. Endoscopic myotomy in the treatment of achalasia. Gastrointest Endosc. 1980. 26(1):8–10. Initial report describing the first human endoscopic myotomy series. Pasricha PJ et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy. 2007;39(9):761–4. Inoue H et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010;42(4):265–71. First 'modern' description of POEM in humans as re-discovered by Dr Inoue. Swanstrom LL et al. Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure. Ann Surg. 2012;256(4):659–67. Describes the long term results of POEM and highlights the importance of post-operative gastroesophageal reflux. Ren Z et al. Perioperative management and treatment for complications during and after peroral endoscopic myotomy (POEM) for esophageal achalasia (EA) (data from 119 cases). Surg Endosc. 2012;26(11):3267–72. Stavropoulos SN, et al. The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM experience. Surg Endosc. 2013. International POEM survey of leading 16 expert centers comparing their methodology and results. Rieder E et al. Intraoperative assessment of esophagogastric junction distensibility during per oral endoscopic myotomy (POEM) for esophageal motility disorders. Surg Endosc. 2013;27(2):400–5. Use of EndoFlip during POEM. Saxena P et al. An alternative method for mucosal flap closure during peroral endoscopic myotomy using an over-the-scope clipping device. Endoscopy. 2013;45(7):579–81. Li H, Linghu E, Wang X. Fibrin sealant for closure of mucosal penetration at the cardia during peroral endoscopic myotomy (POEM). Endoscopy. 2012;44(Suppl 2 UCTN):E215–6.
Curr Gastroenterol Rep (2014) 16:369 19.
Ling T et al. Successful use of a covered, retrievable stent to seal a ruptured mucosal flap safety valve during peroral endoscopic myotomy in a child with achalasia. Endoscopy. 2013;45(Suppl 2 UCTN):E63–4. 20. Kurian AA. et al. Endoscopic suture repair of full-thickness esophagotomy during per-oral esophageal myotomy for achalasia. Surg Endosc. 2013. 21. Rohof WO, Boeckxstaens GE. Treatment of the patient with achalasia. Curr Opin Gastroenterol. 2012;28(4):389–94. 22. Verlaan T et al. Effect of peroral endoscopic myotomy on esophagogastric junction physiology in patients with achalasia. Gastrointest Endosc. 2013;78(1):39–44.
Page 7 of 7, 369 23.• Sharata A et al. Peroral endoscopic myotomy (POEM) is safe and effective in the setting of prior endoscopic intervention. J Gastrointest Surg. 2013;17(7):1188–92. No increase in adverse results during POEM after prevous endoscopic treatment of achalasia. 24. Rawlings A et al. Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial. Surg Endosc. 2012;26(1): 18–26. 25. Kurian AA et al. Peroral endoscopic esophageal myotomy: defining the learning curve. Gastrointest Endosc. 2013;77(5):719–2\. 26. Bloomston M et al. The “learning curve” in videoscopic Heller myotomy. JSLS. 2002;6(1):41–7.
ESOPHAGUS (L GERSON, SECTION EDITOR)
Per-Oral Endoscopic Myotomy (POEM) for Esophageal Achalasia Radu Pescarus & Eran Shlomovitz & Lee L. Swanstrom
Published online: 22 December 2013 # Springer Science+Business Media New York 2013
Abstract Per-oral endoscopic myotomy (POEM) is a new minimally invasive endoscopic treatment for achalasia. Since the first modern human cases were published in 2008, around 2,000 cases have been performed worldwide. This technique requires advanced endoscopic skills and a learning curve of at least 20 cases. POEM is highly successful with over 90 % improvement in dysphagia while offering patients the advantage of a low impact endoscopic access. The main long-term complication is gastroesophageal reflux (GER) with an estimated incidence of 35 %, similar to the incidence of GER post-laparoscopic Heller with fundoplication. Although POEM represents a paradigm shift in the treatment of achalasia, more long-term data are clearly needed to further define its role in the treatment algorithm of this rare disease. Keywords Therapeutical endoscopy . Endoscopic . Achalasia . POEM . Myotomy . Dysphagia
Introduction Achalasia was first described by Sir Thomas Willis in 1674 as a failure of esophageal relaxation (from the Greek chalasis or relaxation) [1]. It is now understood that a loss of inhibitory innervation of the lower esophageal sphincter (LES) results in inadequate relaxation and higher baseline pressures of the LES. Additionally, achalasia also features an absence of esophageal peristalsis. This chronic disease represents the
This article is part of the Topical Collection on Esophagus R. Pescarus : E. Shlomovitz : L. L. Swanstrom (*) Providence Cancer Center, Division of Gastrointestinal and Minimally Invasive Surgery, The Oregon Clinic, Portland, OR, USA e-mail: [email protected]
most common primary motility disorder of the esophagus with various clinical features including regurgitation, dysphagia, retrosternal pain, and weight loss. Despite being a well-known pathology to the foregut surgeon, achalasia remains a rare disease with an annual incidence of approximately 1/100,000 per year [2]. Although the exact etiology of achalasia remains unknown, the most widely accepted theory is that it is caused by an autoimmune attack on the myenteric plexus of the esophagus in individuals with a genetic predisposition [2]. Although no cure has been identified, numerous palliative treatments including medical, endoscopic, and surgical have been proposed, all directed at lowering LES pressure. Medical treatment with nitrate and calcium antagonists is limited due to their poor efficacy and significant side effects [3•, 4, 5•]. However, these smooth muscle relaxants may be helpful in relieving some of the chest pain in patients with vigorous achalasia. Endoscopic treatments have traditionally included Botox injections and pneumatic dilatation (PD). Botox injections at the gastresophageal junction (GEJ) are initially successful in over 90 % of patients; however, the effects last only 6–9 months in the average patient. Botox injections are therefore generally reserved for elderly patients or poor surgical candidates [6]. Pneumatic dilatation is arguably the nonsurgical technique with the highest success rate [7]. A recent multicenter randomized study seemed to demonstrate equivalent clinical success of PD and laparoscopic Heller myotomy (LHM) with Dor fundoplication at 2-year follow-up [8]. In the long-term, however, the failure rate of PD has been shown to be in the region of 50–60 % making LHM the treatment of choice in young or otherwise healthy patients [7]. A new endoscopic technique—the per-oral endoscopic myotomy (POEM) that combines the surgical element of a controlled myotomy with the low impact of endoscopic access—has been establishing itself as a valid alternative in the treatment algorithm of achalasia [9].
369, Page 2 of 7
Historical Background of POEM The first reported endoscopic myotomy performed in 17 achalasia patients was published by Ortega in 1980 [10•]. This was a division of both the mucosa and muscle of the LES, which obviously has an element of risk as it exposes the wound directly to gastric contents and, if too deep, would become a direct hole into the peritoneum or mediastinum. The clinical, manometric ,and radiological post-operative results of all 17 patients were, however, satisfactory with only 3 minor bleeding episodes, which were controlled endoscopically. The medical community, however, did not initially adopt this new technique as it was thought to have too high a potential for complications. It was not until 2007 that Parischa and his team re-invented the procedure and demonstrated its feasibility in four pigs [11]. They improved the safety aspect by creating a mucosal flap to access the muscle. A unique aspect of the procedure they described is the division of only the circular muscle of the esophagus and LES, making this a potentially more “targeted” treatment. The first modern series of patients that underwent POEM for achalasia was described shortly thereafter in 2008 by Dr Inoue and his team [12•]. Currently, around 2,000 cases have been performed worldwide with growing enthusiasm surrounding this endoscopic procedure.
Patient Selection and Operative Indication It is generally recommended that teams beginning a POEM program should do it with institutional review board approval. Our initial exclusion criteria were age under 18 years, inability to undergo general anesthesia, previous esophageal or mediastinal surgery (excluding botox injections and pneumatic dilatations), and a BMI over 40 [13•]. A previous Heller myotomy is no longer considered a contraindication [3•, 14]. Additionally, patients as young as 3 years old have been reported as well as very elderly. Currently, the inability to undergo general anesthesia seems to be the only valid contraindication once the obligatory learning curve has been completed. Although it is thought that patients with achalasia benefit most from POEM, other esophageal pathologies such as diffuse esophageal spasm (DES), non-relaxing hypertensive LES, and Nutcracker esophagus may be palliated by an endoscopic myotomy [9, 15•].
Pre-Operative and Post-Operative Investigations All patients should undergo extensive pre-operative investigations including high-resolution manometry, esophagogastroscopy, and barium swallow study. For outcomes reasons, we repeat these tests 6-months postoperatively. In addition, a 24-h pH study should be obtained
Curr Gastroenterol Rep (2014) 16:369
as iatrogenic gastroesophageal reflux is a possibility and is asymptomatic 50 % of the time. A standardized validated symptom assessment form is completed by all patients. Preoperatively, all patients are put on clear liquid diet for 1 day before the procedure. Patients are treated with oral Nystatin for 5 days pre-operatively to preemptively treat any potential esophageal Candida overgrowth. They receive one prophylactic dose of antibiotics as well as a dose of Dexamethasone at the start of the procedure to minimize mucosal edema, which can make closure of the mucosa more difficult. A contrast upper GI study is performed on post-operative day 1 to rule out any immediate complications. Bloodwork is not routinely necessary after the intervention. The average length of stay is 24 h.
Technical Aspects of POEM Procedure Set-Up and Positioning The procedure is done in the operating room under general anesthesia with endotracheal intubation. CO2 insufflation is used to reduce the risk of air embolism, pneumothorax and subcutaneous emphysema. A high-resolution endoscope, an overtube for stabilization of the endoscope, dissecting cap, injection needle, triangle or hook tip knife, coagulation forceps, and endoscopic clips are essential. Access to an endoscopic suturing device is also extremely helpful in cases of iatrogenic perforations, and can also be used to close the mucosotomy. A thorough cleaning of the esophageal lumen is done before the beginning of the intervention. Sterile saline should be used during the creation of the submucosal channel given the potential mediastinal or peritoneal entry. Communication with the anesthesia team is essential as the patient may develop a tension pneumoperitoneum during the procedure in up to 10 % of the cases. If ventilation pressures increase and tidal volumes decrease significantly, the patient may require a Veres needle decompression of the pneumoperitoneum. Mucosal Entry Initially, the distal end of the dissection 2 cm distal from the GEJ on the lesser curvature is marked with methylene blue upon retroflexion in the stomach (Fig. 1a). A mucosal lift is then performed with saline injection containing a small amount of methylene blue on the right anterior side of the esophageal wall (Fig. 1b). This is followed by a longitudinal 1-to 2-cm mucosotomy. Its orientation is important as transverse incisions are nearly impossible to close with clips. Once the submucosal space is entered, a 12-mm biliary stone extraction balloon is inflated so as to ensure adequate opening of the mucosa and facilitate the introduction of the scope into the
Curr Gastroenterol Rep (2014) 16:369
Page 3 of 7, 369
Fig. 1 Key steps of the POEM procedure. a) Marking the distal end of the dissection 2 cm distal from the GEJ on the short curvature. b) Creation of the submucosal lift. c) Opening of the submucosal channel using sharp dissection. d) Injection of lifting solution through the balloon allows correct delineation of the submucosal plane. e) Sharp dissection of the circular muscle fibers. f) Intraoperative retroflexed view confirming 2 cm extension of myotomy onto stomach wall. g) Multiple clip closure of the mucosal defect
submucosal plane. The next steps are facilitated by the presence of a dissection cap placed on the tip of the scope. A fenestrated cap is preferred as it prevents tissue from being sucked into the cap, which impedes visualization during the procedure. Creation of a Submucosal Tunnel Each step of the procedure requires endoscopic expertise and familiarity with the extra-lumenal anatomy of the
esophagus and proximal stomach, particularly the tunnel creation. It is vital that the submucosal tunnel extends beyond the GEJ for about 2 cm onto the proximal stomach. This submucosal tunnel is created using a combination of spray coagulation, C02 insufflation, and blunt dissection (Fig. 1c). Repeated injections of lifting solution (saline, diluted methylene blue, and epinephrine) through the balloon enables better delineation of the submucosal plane, separates the mucosa and muscle, and acts as a protective heat sink to protect the mucosa (Fig. 1d).
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Identification of GEJ Correct identification of the GEJ is crucial if one wants to obtain an adequate myotomy on the gastric side of at least 2 cm. Various endoscopic findings such as the length of insertion of the endoscope, the presence of palisading mucosal vessels, and the transitory increase and later decrease in the resistance of dissection when passing the LES. One can also identify the relatively increased thickness of the circular muscle bundles of the lower esophageal sphincter, followed by the yellowish characteristic appearance of the submucosal cardial space that also harbors an increased number of vessels. Finally, the discoloration of the cardial mucosa overlying the submucosal tunnel as seen upon retroflexion of the scope in the lumen of the stomach allows for an estimate of the distance from the GEJ (Fig. 1f). Circular Muscle Myotomy The selective myotomy of the circular bundles starts 2 cm distal to the mucosal entry site. Careful use of the triangle tip knife or other spray coagulation devices is paramount as both the mucosa on one side and the longitudinal muscle layer on the other side should be preserved (Fig. 1e). Inoue et al. originally described a 10-cm myotomy on the esophageal side and 2-cm below the GEJ [12•]. The extent of the myotomy can be modified by the interpretation of the endoscopic images and by the pre-operative manometry results (Fig. 2a, b). Given the high incidence of GER post-POEM, our team and others have attempted to decrease the length of the myotomy, except for cases of vigorous achalasia where a longer myotomy is warranted. This tailored approach is facilitated by a new endoluminal functional lumen-imaging probe (EndoFLIP; Crospon, Galway, Ireland) that measures the GEJ distensibility before and after the selective myotomy [16•] (Fig. 2c). Closure of the Mucosotomy The mucosal entry site is closed with endoscopic clips at the end of the procedure (Fig. 1g). Usually 1.5–2 cm in length, the opening is closed with several clips starting at the distal end ensuring complete closure of the defect. A few alternative closure methods have been described in situations where the usual endoscopic clips fail. Both over-the-scope clips (OTSC) [17] as well as fibrin sealants in the case of perforation of the gastric cardia [18] have been described. Another option for mucosotomies that cannot be closed is a covered stent [19]. Finally, an endoluminal suturing device (OverStitch; Apollo Endosurgery, Austin, TX, USA) was first employed for a twolayered closure of an inadvertent full-thickness esophagotomy during a POEM procedure [20]. It is advisable that this endoscopic suturing device is available for POEM cases as it represents a good alternative to clips in difficult situations.
Fig. 2 a) Comparison between pre and post-POEM high-resolution manometry findings in Chicago Type I achalasia. b) Comparison between pre and post-POEM high-resolution manometry findings in Chicago Type II achalasia. c) Example of intra-operative EndoFlip use before and after a POEM procedure
Post-Operative Care The morning of post-operative day 1, all patients undergo an upper GI contrast study to rule out a mucosal defect and to
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ensure adequate opening of the GEJ post myotomy. If clinically well and free of radiological evidence of complications, the patients are discharged on post-operative day 1 with instructions to follow a liquid and pureed diet for 1 week. At 6-months post-intervention, the patient is re-scheduled for follow-up manometry, pH study, and esophagogastroscopy. In the long term, we recommend an upper endoscopy to be done every 5 years in all achalasia patients, given the slightly increased risk for esophageal carcinoma [21].
Complications Short-Term Complications Obviously, the most feared complication would be a postoperative mediastinal leak. Fortunately, the 2 layers of protection (preserved longitudinal muscle and intact mucosa) make this complication rare in all published series. Perforation of the longitudinal muscular layer with complete communication with the mediastinum or abdominal cavity happens relatively frequently due to the tenuous nature of the longitudinal muscle layer. It is also not repairable endoscopically, and therefore is ignored when it happens. On the other hand, if there are mucosal perforations they should be carefully closed. A clinically significant pneumoperitoneum or pneumothorax manifested by difficult ventilation may require decompression with a Veres needle or chest drain. Rarely, excessive hypercarbia resulting from the extended CO2 administration may delay the post-operative extubation especially in medically marginal patients. An incomplete closure of the mucosotomy is usually diagnosed on the upper GI study done postoperatively. This is an indication for endoscopic evaluation and repair by the addition of clips. Any mucosal perforation elsewhere along the myotomy has to be followed by careful closure. Long-Term Complications One of the most common long-term complications seen with this procedure is gastroesophageal reflux (GER). In our initial experience, 46 % of patients demonstrated an abnormal pH study post-operatively and overall 50 % of the cohort had either pH or endoscopic evidence of reflux [13•]. Similarly, a rate of up to 60 % endoscopic evidence of reflux (pH study was not performed) was published by a European team [22]. Our more recent experience has shown an objective incidence of around 35 %, possible due to tailoring our myotomy length based on Endoflip measurements. This is comparable to laparoscopic Heller with fundoplication [13•].
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Results More than 2,000 cases of POEM have been performed worldwide. There are at least 16 centers performing POEM with more than 25 different operators [15•]. Children as young as 3 years and elderly patients up to 97 years of age have undergone the POEM procedure. The mean duration of the case is between 90 and 120 min and varies with the experience of the operator [15•]. POEM after prior endoscopic treatment (Botox or balloon dilation) is safe as demonstrated by the absence of statistical difference between the length of the procedure or the incidence of complications [23•]. POEM after previous Heller myotomy has been performed in a few centers and seems to be associated with increased difficulty and increased complication rate, but no difference in clinical results [15•]. Intermediate-term clinical success at an average of 9.3 months after POEM is high, with dysphagia relief ranging from 90 to 100 % and an average of 98 % [15•]. GER symptoms are present in 0–44 % of patients, with a reported anti-acid use of 0–50 % post-POEM. Endoscopic evidence of erosive esophagitis is present in 0–43 % and positive pH studies were present in 0–38 % of patients. Although these numbers reflect a high incidence of post-operative GER, they are in fact similar to the 21–42 % of abnormal pH studies postlaparoscopic Heller and partial fundoplication [24]. When no complications arise, the patients leave the hospital in the morning of the first post-operative day. Usually no pain medications are necessary. Patients return to work an average of 3 days after the intervention.
Learning Curve in Performing POEM The POEM procedure requires a unique set of skills. While having advanced endoscopic skills is a sine qua non, the team performing the procedure must be familiar with the gastroesophageal junction and the physiopathology of achalasia, as well as having a well-defined algorithm when dealing with the most frequent complications. A learning curve of approximately 20 cases has been proposed for an experienced endoscopist [25]. Indeed, the length of the procedure and the incidence of inadvertent mucosotomies seem to plateau after 20 cases [25]. This is similar to the learning curve postlaparoscopic Heller myotomy as described by Bloomston in 2002 [26]. Training in the laboratory may facilitate the acquisition of the skills necessary to perform the POEM procedure. The pig explant model containing the esophagus and stomach represents a good inanimate model. Once the training on the explant model is completed, one should further perfect the technique using a live porcine model. Cadaver models are also
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a possibility with the advantage of a more realistic anatomy. Finally, a large part of the skill set necessary to perform endoscopic submucosal dissections (ESD) is also necessary for POEM. Mastering ESD may be an obligatory step before becoming a POEM expert [9].
Future Directions
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References Papers of particular interest, published recently, have been highlighted as: • Of importance
1. 2.
One of the most important long-term complications of the POEM procedure, the iatrogenic GER, needs to be better studied. Objective endoscopic and pH measurements are necessary along with longer post-operative follow-up. Technical modifications such as tailoring the length of the myotomy based on intra-operative electrophysiological measurements will hopefully reduce the incidence of this problem. Longerterm follow-up will further define whether their post-operative symptoms will be adequately controlled medically. In the future, multi-center prospective randomized studies comparing laparoscopic Heller myotomy and POEM, as well as POEM versus balloon dilation, would further define the unique role of POEM in the treatment algorithm of this rare disease. Equally important will be to define the therapeutic success of POEM in the other non-achalasia esophageal motility disorders.
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9. 10.•
Conclusion 11.
The POEM procedure represents a clear paradigm shift in the treatment of achalasia and is arguably among the most successful natural orifice translumenal endoscopic surgery (NOTES) procedures. Through its minimally invasive character, it offers excellent palliation in achalasia patients with good clinical results and low adverse events. This endoscopic myotomy procedure requires excellent endoscopic skills and a definite learning curve of at least 20 cases. This will undoubtedly limit its adoption to high-volume esophageal centers. Further studies are needed with greater numbers of patients and longer follow up. Equally important will be to perfect the inanimate and animal models to create adequate training environments for the future POEM providers. Compliance with Ethics Guidelines Conflict of Interest Dr. Shlomovitz declares no conflicts of interest. Dr. Swanstrom has served as a consultant for Olympus and received a grant from Boston Scientific. Dr. Pescarus has no conflicts of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by the author.
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Cash BD, Wong RK. Historical perspective of achalasia. Gastrointest Endosc Clin N Am. 2001;11(2):221–34. v. Gockel HR et al. Achalasia: will genetic studies provide insights? Hum Genet. 2010;128(4):353–64. Eleftheriadis N et al. Training in peroral endoscopic myotomy (POEM) for esophageal achalasia. Ther Clin Risk Manag. 2012;8: 329–42. Good comprehensive review about POEM from a practical perspective. Beck WC, Sharp KW. Achalasia. Surg Clin North Am. 2011;91(5): 1031–7. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol. 2013. Most recent American College of Gastrenterology guidelines for the treatment of achalasia. Chuah SK et al. 2011 update on esophageal achalasia. World J Gastroenterol. 2012;18(14):1573–8. Allaix ME, Patti MG. What is the best primary therapy for achalasia: medical or surgical treatment? Who owns achalasia?. J Gastrointest Surg. 2013. Boeckxstaens GE et al. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med. 2011;364(19):1807–16. Swanstrom LL. Peroral endoscopic myotomy for treatment of achalasia. Gastroenterol Hepatol (N Y). 2012;8(9):613–5. Ortega JA, Madureri V, Perez L. Endoscopic myotomy in the treatment of achalasia. Gastrointest Endosc. 1980. 26(1):8–10. Initial report describing the first human endoscopic myotomy series. Pasricha PJ et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy. 2007;39(9):761–4. Inoue H et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010;42(4):265–71. First 'modern' description of POEM in humans as re-discovered by Dr Inoue. Swanstrom LL et al. Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure. Ann Surg. 2012;256(4):659–67. Describes the long term results of POEM and highlights the importance of post-operative gastroesophageal reflux. Ren Z et al. Perioperative management and treatment for complications during and after peroral endoscopic myotomy (POEM) for esophageal achalasia (EA) (data from 119 cases). Surg Endosc. 2012;26(11):3267–72. Stavropoulos SN, et al. The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM experience. Surg Endosc. 2013. International POEM survey of leading 16 expert centers comparing their methodology and results. Rieder E et al. Intraoperative assessment of esophagogastric junction distensibility during per oral endoscopic myotomy (POEM) for esophageal motility disorders. Surg Endosc. 2013;27(2):400–5. Use of EndoFlip during POEM. Saxena P et al. An alternative method for mucosal flap closure during peroral endoscopic myotomy using an over-the-scope clipping device. Endoscopy. 2013;45(7):579–81. Li H, Linghu E, Wang X. Fibrin sealant for closure of mucosal penetration at the cardia during peroral endoscopic myotomy (POEM). Endoscopy. 2012;44(Suppl 2 UCTN):E215–6.
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Ling T et al. Successful use of a covered, retrievable stent to seal a ruptured mucosal flap safety valve during peroral endoscopic myotomy in a child with achalasia. Endoscopy. 2013;45(Suppl 2 UCTN):E63–4. 20. Kurian AA. et al. Endoscopic suture repair of full-thickness esophagotomy during per-oral esophageal myotomy for achalasia. Surg Endosc. 2013. 21. Rohof WO, Boeckxstaens GE. Treatment of the patient with achalasia. Curr Opin Gastroenterol. 2012;28(4):389–94. 22. Verlaan T et al. Effect of peroral endoscopic myotomy on esophagogastric junction physiology in patients with achalasia. Gastrointest Endosc. 2013;78(1):39–44.
Page 7 of 7, 369 23.• Sharata A et al. Peroral endoscopic myotomy (POEM) is safe and effective in the setting of prior endoscopic intervention. J Gastrointest Surg. 2013;17(7):1188–92. No increase in adverse results during POEM after prevous endoscopic treatment of achalasia. 24. Rawlings A et al. Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial. Surg Endosc. 2012;26(1): 18–26. 25. Kurian AA et al. Peroral endoscopic esophageal myotomy: defining the learning curve. Gastrointest Endosc. 2013;77(5):719–2\. 26. Bloomston M et al. The “learning curve” in videoscopic Heller myotomy. JSLS. 2002;6(1):41–7.
