Peroral endoscopic myotomy as salvation technique post‐ ...

Digestive Endoscopy 2018; 30: 52–56

doi: 10.1111/den.12918

Original Article

Peroral endoscopic myotomy as salvation technique post-Heller: International experience Amy Tyberg,1 Reem Z. Sharaiha,1 Pietro Familiari,6 Guido Costamagna,6 Fernando Casas,8 Nikhil A. Kumta,1 Maximilien Barret,9 Amit P. Desai,1 Felice Schnoll-Sussman,1 Payal Saxena,2 Guadalupe Martınez,10 Felipe Zamarripa,10 Monica Gaidhane,1 Helga Bertani,7 Peter V. Draganov,3 Valerio Balassone,11 Ahmed Sharata,4 Kevin Reavis,5 Lee Swanstrom,4 Martina Invernizzi,13 Stefan Seewald,13 Hitomi Minami,12 Haruhiro Inoue11 and Michel Kahaleh1 1

Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, 2Gastroenterology, Johns Hopkins, Baltimore, 3Gastroenterology, Gainesvillle Medical Center, Gainesville, 4Gastroenterology, Oregon Clinic, 5 Gastroenterology, Portland Clinic, Portland, USA, 6Digestive Endoscopy Unit, Catholic University, Rome, 7 Gastroenterology, Locale Modena, Modena, Italy, 8Gastroenterology, Bogota General Hospital, Bogota, Colombia, 9Gastroenterology, Pompidou Clinic, Paris, France, 10Gastroenterology, Juarez Hospital, Mexico City, Mexico, 11Gastroenterology, Showa University Northern Yokohama Hospital, Tokyo, 12Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan and 13Gastroenterology, Klinik Hirslanden, Zurich, Switzerland Background: Treatment for achalasia has traditionally been Heller myotomy (HM). Despite its excellent efficacy rate, a number of patients remain symptomatic post-procedure. Limited data exist as to the best management for recurrence of symptoms post-HM. We present an international, multicenter experience evaluating the efficacy and safety of post-HM peroral endoscopic myotomy (POEM).

Results: Fifty-one patients were included in the study (mean

Methods: Patients who underwent POEM post-HM from 13

Conclusion: For patients with persistent symptoms after HM,

centers from January 2012 to January 2017 were included as part of a prospective registry. Technical success was defined as successful completion of the myotomy. Clinical success was defined as an Eckardt score of ≤3 on 12-month follow up. Adverse events (AE) including anesthesia-related, operative, and postoperative complications were recorded.

POEM is a safe salvation technique with good short-term efficacy. As a result of the challenge associated with repeat HM, POEM might become the preferred technique in this patient population. Further studies with longer follow up are needed.

INTRODUCTION

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CHALASIA IS A rare esophageal motility disorder that is caused by the loss of myenteric neurons resulting in aperistalsis and impaired relaxation of the lower esophageal sphincter (LES).1 This results in uncoordinated flow of digested food into the stomach and subsequent stasis of food and secretions into the esophagus. The mainstay of treatment for achalasia has traditionally been surgical Heller

Corresponding: Michel Kahaleh, Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, NY 10021, USA. Email: [email protected] Received 23 September 2016; accepted 4 July 2017.

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age 54.2, 47% male). Technical success was achieved in 100% of patients. Clinical success on long-term follow up was achieved in 48 patients (94%), with a mean change in Eckardt score of 6.25. Seven patients (13%) had AE: six experienced periprocedural mucosal defect treated endoscopically and two patients developed mediastinitis treated conservatively.

Key words: achalasia, endoscopy, esophagus, Heller myotomy, peroral endoscopic myotomy (POEM)

myotomy (HM), which involves laparoscopically cutting the cardia muscle fibers on the anterior side and carrying out fundoplication to reduce the risk of gastroesophageal reflux.2 More recently, peroral endoscopic myotomy (POEM) has emerged as an alternative therapeutic option in which an esophageal submucosal tunnel is formed to allow for endoscopic myotomy on either the anterior or posterior side.3 Despite the excellent efficacy rate of surgical myotomy, approximately 10% of patients develop recurrent symptoms post-procedure.4 The best management for such patients remains controversial. Pneumatic balloon dilation (PD) is often used as a salvage technique, but long-term results show variable and limited efficacy and the fibrosis caused by

© 2017 Japan Gastroenterological Endoscopy Society


repeated dilations may compromise a subsequent re-myotomy.4 Repeat HM has also been carried out, but it is technically challenging and can be associated with lower efficacy rates and higher complication rates even in experienced hands.5 Carrying out POEM post-HM avoids the complexities of reoperating in the same plane by allowing for a second myotomy to be carried out on the opposite orientation of the initial surgical myotomy. This also potentially increases efficacy by creating a longer and more complete myotomy. However, scarring from prior surgery could potentially increase procedural difficulty during POEM similar to repeat HM. Preliminary data suggest that POEM post-HM is efficacious and safe.6–10 We present the first multicenter, international experience on the short-term efficacy and safety of POEM post-HM.

POEM as salvation technique post-Heller

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intermittent injection and dissection to create a tunnel (Figs 1, 2). A 12–15-cm myotomy was then carried out extending through the LES (Fig. 3). The myotomy typically included the circular layer in the proximal and midportions of the esophagus, and was full thickness (circular and longitudinal) in the lower third of the esophagus. All

METHODS Study overview

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LL CONSECUTIVE PATIENTS who underwent POEM post-HM from 13 centers in nine countries and four continents from January 2012 to January 2017 were included. All patients were enrolled in a prospective registry (NCT02162589) under IRB approval. All patients signed informed consent prior to the procedure. Demographic information, disease-related information, procedural details, and clinical follow up were documented for all patients. Technical success was defined as successful completion of the myotomy. Clinical success was defined as an Eckardt score of ≤3 on at least 12-month postprocedure follow up. Barium esophagogram and/or manometry findings were recorded. Adverse events including anesthesia-related, operative, and postoperative complications were recorded.

Figure 1 Endoscopic view of tunnel with exposure of the posterior muscularis.

Procedure technique All procedures were carried out under general anesthesia with carbon dioxide (CO2) insufflation by endoscopists with expertise in carrying out POEM. A complete upper endoscopy was carried out. In some cases, an overtube was advanced into the esophagus and location of the gastroesophageal junction (GEJ) was noted. A transparent cap was attached to the endoscope. Approximately 12 cm proximal to the GEJ, a submucosal injection was made posteriorly with a mixture of crystalloid and indigocarmine or methylene blue. A mucosal incision over the bleb was done to enter the submucosa. The submucosal space was then dissected with an electrocautery knife, either Hybrid Knife (ERBE, T€ ubingen, Germany) or Triangular Knife (Olympus Center Valley, PA, USA) using

Figure 2 Endoscopic view of the fundoplication infiltrated with normal saline and indigocarmine from the injection into the tunnel created through the gastroesophageal junction.


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pressure (IRP) of 30.7. Mean Eckardt score pre-procedure was 7.98 2.11. A total of 15 (29%) patients had a sigmoid esophagus.

Technical success Technical success was achieved in 100% of patients (Table 1). Clips were used for closure of the submucosal tunnel in (48) 94% of patients. Endoscopic suturing was placed in one patient, and an over-the-scope clip was placed in two patients.

Clinical success

Figure 3 Endoscopic view of full-thickness myotomy exposing the serosa.

peroral endoscopic myotomies were carried out posteriorly at the 5–6 o’clock position. Needle decompression of the abdomen was carried out during the procedure if CO2 retention was suspected. After successful myotomy, the mucosal entry site was closed with either through-thescope hemostatic clips, endoscopic suturing (OverStitch; Apollo Endosurgery), or over-the-scope clips (OTSC; Ovesco, T€ubingen, Germany) at the discretion of the endoscopist.

RESULTS

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TOTAL OF 51 patients were included in the study (mean age 54.2, 47% male). Thirteen patients (25%) had type 1 achalasia, 29 (57%) had type 2 achalasia, six (12%) had type 3 achalasia, and three (6%) had other esophageal dysmotility disorders (two nutcracker and one diffuse esophageal spam). Forty-three (84%) patients had a laparoscopic Heller myotomy, whereas eight (16%) patients had a Heller via laparotomy. Forty-five (88%) patients received a Dor fundoplication, whereas six (12%) patients underwent Nissen as antireflux procedures. Mean duration of disease was 11.2 years. Mean time between HM and POEM was 113.5 months (9.5 years; range 2 months to 56 years). All patients had a barium swallow suggestive of recurrent achalasia prior to POEM. All patients except one patient (98%) had manometry with an average integrated relaxation


Clinical success of an Eckardt score ≤3 was achieved in 49/51 patients (96%). Mean Eckardt score post-procedure was 1.72 1.5 with a mean difference of 6.25 (t-value = 17.41013, P < 0.00001). Follow-up duration was an average of 24.4 months (range 12–52). All patients had follow-up duration of at least 1 year, whereas 29 patients (57%) had follow-up duration of at least 24 or more months. In the three patients who did not achieve clinical success, two had a decrease in Eckardt score by 50% (10 to 5; 9 to 4), one achieved clinical success with an Eckardt score of 2 on 6-month follow up, and one had a massively dilated esophagus and required serial dilations afterwards.

Table 1 Characteristics of patients who underwent POEM post-HM No. patients

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Sex (M) Mean age (years) Type of achalasia Type I Type II Type III Other Technical success Clinical success Eckardt ≤ 3 Change in Eckardt score Significant adverse events

24 (47%) 54.2

Mean time between myotomies (months) Average follow up (months)

13 29 6 3 51 (100%) 48 (94%) 6.25 6 mucosal defects 2 mediastinitis treated conservatively 113.5 months 24.4 months

HM, Heller myotomy; POEM, peroral endoscopic myotomy.


Adverse events Seven patients (14%) had AE: six experienced periprocedural mucosal defect treated with endoscopic clips and two patients developed mediastinitis treated conservatively with i.v. antibiotherapy and nasogastric feeding. There were no deaths. No POEM were aborted or required laparoscopic conversion or assistance in either group.

DISCUSSION

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PTIMAL MANAGEMENT FOR patients who develop recurrent or persistent symptoms of achalasia after surgical myotomy remains controversial. Pneumatic dilation is traditionally carried out as the first salvage technique, but is associated with inconsistent results and overall limited efficacy. Recently, Amani et al. reported a 70% response rate for patients with recurrent symptoms post-HM.11 However, previous studies have found more variable and dismal efficacy rates ranging from 9% (1 of 11 patients)6 to 23% (5 of 22 patients).12,13 After PD, repeat surgical intervention has been the preferred approach. However, as is well known, reoperating in a previous surgical plane increases surgical complexity and consequently increases complications and limits efficacy.5 Endoscopic myotomy, or POEM, offers a potentially safer and more efficacious option. Because POEM can be carried out in either an anterior or posterior orientation, it allows the endoscopist the ability to avoid the previously intervened on anterior surgical plane by opting for a posterior myotomy. In doing so, an efficacy benefit could also be achieved from the creation of a fully circumferential myotomy. Several small comparative studies of patients with recurrent symptoms post-HM who underwent repeat endoscopic or surgical myotomy have shown that POEM postHM is safe and efficacious. Fumagalli et al. found that six of six patients had resolution of symptoms after repeat POEM compared to seven of nine with repeat HM. Additionally, they documented three esophageal perforations in the repeat HM group compared to none in the repeat POEM group.8 Similarly, Vigneswaran et al. found equal efficacy in three patients with a redo HM and five patients with a redo POEM, but one major adverse event in the HM group.10 In two single-center studies looking at 11 and 12 patients who underwent POEM after HM by Onimaru et al. and Zhou et al. respectively, clinical success was achieved in 100% and 91.7% of patients with no major adverse events recorded.6,7 Our study represents the largest and the first multicenter experience of patients who underwent POEM after HM.

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Although the follow-up time post-procedure is short, we found an overall clinical success rate of 94% with a significant decrease in Eckardt score of 6.25. Additionally, in the patients who did not achieve clinical success, all three had a >50% decrease in Eckardt score and one achieved clinical success at 6 months follow up. Only three patients required dilation post repeat POEM and were included as failures. Interestingly, no patients in our study had significant adverse events despite having undergone a previous surgical myotomy. Only two mediastinitis were encountered and managed conservatively with antibiotics and nasogastric feeding. This is similar to rates described in patients undergoing de novo POEM, and far superior to what is reported for redo HM. Although 94% of patients achieved clinical success, true long-term efficacy remains unknown. However, prior studies assessing the efficacy of POEM as the initial therapy have shown persistent efficacy over time; similar results would be expected from a POEM done after a HM as the myotomy is being carried out on previously untouched muscle fibers similar to a de novo POEM. In conclusion, for patients with persistent symptoms after HM, POEM is a safe salvation technique with excellent short-term efficacy. As a result of the challenges associated with repeat HM, POEM might become the preferred technique in this patient population. Additional studies with longer follow-up time are needed.

CONFLICTS OF INTEREST

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ICHEL KAHALEH MD: has received grant support from Boston Scientific, Fujinon, EMcison, Xlumena Inc., W.L. Gore, MaunaKea, Apollo Endosurgery, Cook Endoscopy, ASPIRE Bariatrics, GI Dynamics, NinePoint Medical, Merit Medical, Olympus and MI Tech. He is a consultant for Boston Scientific, Xlumena Inc., Concordia Laboratories inc, ABBvie, and MaunaKea Tech. Reem Z. Sharaiha MS is a consultant for Apollo Endosurgery. All other authors have no conflicts of interest to report.

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