Peroral endoscopic myotomy in children with achalasia: A review of the literature

Abstract

Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter (LES) to relax, accompanied by the loss of peristalsis in the esophageal body. Although more prevalent in adults, pediatric achalasia poses unique diagnostic challenges due to its atypical presentation. Peroral Endoscopic Myotomy (POEM) has emerged as a minimally invasive alternative to laparoscopic Heller myotomy for managing achalasia, particularly in children, but its efficacy and safety remain under-investigated. A comprehensive literature review was conducted to assess the role of POEM in pediatric achalasia, focusing on procedure efficacy, clinical outcomes, and safety. Key parameters included pre- and post-procedure Eckardt scores and adverse events. Comparison of outcomes with alternative interventions, such as laparoscopic myotomy and pneumatic dilation were also investigated. Currently, POEM achieves high clinical success in pediatric patients, with significant reduction in post-procedure Eckardt scores and LES pressures. Clinical success rates of up to 90% with durable symptom relief have been observed over follow-up exceeding one year. Common adverse events include mucosal injury, capnoperitoneum, and postoperative reflux. This comprehensive review reveals that POEM is as effective as laparoscopic myotomy but offers shorter hospital stay and reduced recovery time at the cost of a higher complication rate. POEM is an effective treatment for pediatric achalasia, providing durable symptom relief, comparable to traditional interventions. Future research should focus on the identification of pediatric patients that would benefit the most from POEM.

Key Words: Achalasia; Myotomy; Peroral endoscopic myotomy; Endoscopy; Pediatric achalasia

Core Tip: In pediatric patients with achalasia, peroral endoscopic myotomy (POEM) has shown high clinical success rates, achieving significant reduction in post-procedure symptoms and esophageal pressures. The current literature shows clinical success of up to 90% with durable symptom relief lasting over a year. Compared to traditional treatments, POEM offers shorter hospital stays and reduced recovery times at the cost of a higher complication rate. As the field continues to evolve, future research should focus on minimizing potential side effects and identifying children that will benefit the most from this procedure.

INTRODUCTION

Achalasia is a rare primary motility disorder of the esophagus[1], characterized by the loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). Achalasia impairs the passage of solid food and liquids into the stomach, causing symptoms such as dysphagia, regurgitation, chest pain and weight loss[2,3]. Achalasia in children is rare, with an estimated annual incidence of 2 to 31 cases per 10⁷ children, approximately 10 times less frequent than in adults[2].

Children with achalasia most commonly present with dysphagia, regurgitation, chest pain, emesis, odynophagia, weight loss/poor weight gain or impaired growth[4]. The symptoms are less specific in younger children[5] and include refusal of oral intake, failure to thrive, oropharyngeal dysphagia, aspiration, vomiting, abdominal pain, and nocturnal cough[6]. Non-specific symptoms may lead to misdiagnosis[7] and diagnostic delay (up to 6-10 years)[5].

Achalasia is related to an imbalance between the inhibitory and excitatory activity of esophageal nerve cells, as a result of the degeneration of the inhibitory myenteric plexus, that innervates the LES and the esophageal body[8]. Loss of inhibitory nitric oxide-producing and cholinergic neurons results in the loss of esophageal peristaltic waves and impaired LES relaxation. The pathogenetic mechanisms of neuronal degeneration in achalasia have not been completely characterized. Previous studies have suggested an association between achalasia and viral or parasitic infections[9-13]. The risk of achalasia is greater in people with allergic disorders, adrenal insufficiency, Allgrove syndrome (achalasia, adrenal deficiency, alacrimation)[14,15], and neurological disorders, such as familial dysautonomia[16,17]. A genetic predisposition has also been suggested, based on cases associated with Down syndrome or familial achalasia. Autoimmune mechanisms have also been suspected to cause degeneration of esophageal nerve cells[16,17].

Achalasia may be diagnosed with a barium swallow study that demonstrates a dilated esophagus with tapering of the distal end (‘bird’s beak’)[6,18]. However, the diagnostic gold standard is esophageal manometry[19] (Table 1). Achalasia is classified in 3 main subtypes according to the Chicago classification: (I) Achalasia characterized by absent distal esophageal pressurization; (II) Achalasia characterized by panesophageal pressurization; and (III) Achalasia characterized by 2 or more spastic contractions with or without periods of pressurization[20,21]. Achalasia subtype I is associated with elevated integrated relaxation pressure (IRP) (> 15 mmHg) and complete absence (100%) of peristalsis, while subtype II is also associated with increased IRP and patients commonly present with weight loss. Patients with achalasia subtype III more commonly present with chest pain. Of note, this subtype is not widely accepted, particularly in pediatric patients where it is exceedingly rare[22]. The subtype classification of achalasia has significant clinical implications, because patients in subtype II are more likely to respond to operative intervention[23]. However, it is important to note that occasionally pediatric patients may not be able to tolerate high-resolution manometry[24].

Table 1 Achalasia diagnosis, classification and clinical implications.

Aspect	Details
Diagnostic methods	1 Barium swallow study: Demonstrates dilated esophagus with tapering distal esophagus ("bird's beak sign")
	2 Esophageal manometry: Gold standard for diagnosis
Achalasia subtypes	Subtype I: Absent distal esophageal pressurization
	Subtype II: Panesophageal pressurization
	Subtype III (A, B, C, D): Spastic contractions (≥ 2) with or without periods of pressurization
	A: Spastic achalasia: Premature/spastic contractions with impaired LES relaxation
	B: Hypercontractile achalasia: High amplitude and long-duration contractions with incomplete LES relaxation
	C: Segmental achalasia: Abnormal contractions limited to specific segments (commonly distal third)
	D: Peristaltic achalasia: Proximal esophageal peristalsis retained with distal esophagus spastic activity
Clinical presentation	Subtype I: 100% failure of peristalsis
	Subtype II: Increased IRP, commonly associated with weight loss
	Subtype III: Chest pain common symptom
Clinical implications	Patients with subtype II are more likely to respond to operative interventions

LES: Lower esophageal sphincter; IRP: Integrated relaxation pressure.

A new endoscopic classification, that has not been widely accepted, was proposed by Li and Linghu[25] in 2013 (Ling classification). This classification is mainly used for the selection of patients eligible for endoscopic myotomy, and includes 3 types: (I) No multi-ring, crescent-like structure or diverticulum structure; (II) Presence of multi-ring or crescent-like structure but without diverticulum structure; and (III) Presence of diverticulum structure[26,27]. Type III achalasia is the most rare (approximately 10% of patients with achalasia) and the most difficult to treat[27].

Severe complications of achalasia in children include aspiration pneumonia, malnutrition due to inadequate oral intake, esophagitis, esophageal perforation, and increased risk of esophageal squamous cell carcinoma. The management of achalasia in children may include medical treatments (botulinum toxin injection, oral nitrates and calcium channel blockers), laparoscopic Heller Myotomy (LHM)[28], pneumatic dilation (PD)[29], and peroral endoscopic myotomy (POEM). Currently, there is inadequate evidence regarding the optimal treatment of pediatric achalasia and there is high heterogeneity in its management worldwide. This review provides an up-to-date overview of the utilization of POEM in children with achalasia, based on a thorough analysis of existing literature.

METHODOLOGY

A systematic literature search was conducted (last search date: November 11, 2024) in PubMed with combinations and variations of the following keywords: "POEM", "per-oral endoscopic myotomy", “peroral endoscopic myotomy”, "pediatric achalasia", “child* achalasia”. Original research studies that involved pediatric populations (< 18 years) or mixed populations with pediatric data were included. Studies that only included adults (> 18 years) were excluded. Data extraction was performed independently by two reviewers to assess study design, patient characteristics, and outcomes. The narrative synthesis was structured around key variables of interest, such as efficacy, procedure-specific details, adverse events, and long-term outcomes.

THE POEM PROCEDURE: DESCRIPTIVE ANALYSIS OF THE PROCEDURE

In 2007, Pasricha et al[30] described the efficacy of submucosal endoscopic esophageal myotomy in animal models of achalasia, and subsequently the POEM procedure was introduced as a less invasive alternative to LHM in Japan in 2008 by Inoue et al[31]. Following the establishment of its efficacy and safety in adult patients, the POEM procedure has become an important alternative treatment for achalasia in children[32].

POEM requires careful pre-procedure preparation to ensure optimal outcomes in pediatric patients. The day before POEM pediatric patients receive a liquid diet and prophylactic antibiotics are given prior to scope insertion. POEM in pediatric patients is most commonly performed under general anesthesia via endotracheal intubation and a standard single-channel endoscope[33,34]. The preferred insufflating agent is carbon dioxide[35]. POEM is a procedure that is associated with unique challenges for anesthesiologists and requires specialized anesthesia management considering the risk of pneumomediastinum/pneumoperitoneum[36]. The average duration of POEM is 63 minutes[3]. The basic steps of POEM include: (1) Insertion of the endoscope into the submucosal space through a mucosotomy; (2) Creation of a submucosal tunnel distally; (3) Myotomy performed with electrocautery; (4) Inspection of the tunnel after the myotomy; and (5) Repair of the mucosal incision with endoscopic clips[37] (Figure 1). The circular muscle layer is incised proximally 2-3 cm beyond the mucosal incision in the esophagus and distally to 2-3 cm into the gastric cardia[35], and the myotomy length in the pediatric literature ranges between 3-21 cm[16,34,38]. The preservation of the external longitudinal muscle fibers during the myotomy and the closure of the mucosal incision are two steps of utmost importance to minimize potential complications during POEM[31]. Postoperatively, the routine use of antibiotics has not been shown to prevent infection[39].

Figure 1 Schematic representation of peroral endoscopic myotomy steps. A: Insertion of the endoscope into the submucosal space through a mucosotomy; B: Creation of a submucosal tunnel distally; C: Myotomy performed with electrocautery; D: Inspection of the tunnel after the myotomy; E: Repair of the mucosal incision with endoscopic clips.

Recent studies have sought to optimize the efficacy, duration, and safety of POEM by defining the endpoint of POEM or through the use of different scopes. One such study by Rafeeqi et al[40] used endoFLIP, a device that uses a sensory balloon to obtain measurements of the area and pressure inside the esophagus, and demonstrated that endoFLIP is a valuable tool in diagnosing and managing achalasia. Another innovative approach to POEM has been proposed by Bapaye et al[41], who successfully performed the procedure in an 18-month old child using a transnasal ultra-slim gastroscope, instead of a standard gastroscope due to technical and/or anatomical space constraint. Lastly, in 2018, Nabi et al[42] conducted a retrospective study in 10 pediatric patients with achalasia (4 with type I, 5 with type II and 1 patient with type III) using a triangular knife with water jet and reported decreased procedure duration and clinical success in 9 patients with significant reduction in Eckardt scores at 1 month after POEM.

INDICATIONS AND CONTRAINDICATIONS OF POEM IN CHILDREN

POEM is indicated in children with achalasia, including type III achalasia because it allows for a more extensive myotomy compared to LHM[43,44], and it is the next treatment in patients who have undergone previous treatments for achalasia, such as botulinum toxin injection, pneumatic dilation, and LHM[45]. The contraindications to perform POEM include prior irradiation to the mediastinum, severe pulmonary disease, coagulopathy, thrombocytopenia (< 30000-50000/μL), prior endoscopic mucosal resection, ablative therapy or mucosal resection that has compromised the integrity of the esophageal mucosa, and portal hypertension[6,45].

PRIMARY OUTCOMES: EFFICACY OF POEM IN CHILDREN

Current experience with POEM indicates that the technique can be applied successfully in pediatric populations[35]. The Eckardt score system that ranges between 0-12 and is a composite of points assigned to 4 symptoms (dysphagia, regurgitation, chest pain, and weight loss), remains the key indicator of clinical efficacy in the treatment of achalasia. Clinical success is defined as an Eckardt score less than 3[37,46].

Large studies with mixed pediatric and adult data have shown promising results for POEM. A retrospective study by Ramchandani et al[47] analyzed data from a mixed population of 220 adult and pediatric patients (mean age: 39 years, range 9-74) between 2013-2014 undergoing POEM in a single center and had a clinical success rate of 96%. In another study, Shiwaku et al[48] conducted a retrospective analysis of 100 patients (mean age 48.2 years, range 9-91 years) with a 3-month follow up and reported a mean pre-procedure and post-procedure IRP of 33.5 ± 15.2 mmHg and 15.3 ± 6.5 mmHg, respectively, significantly decreased Eckardt score from 5.9 ± 2.5 to 0.8 ± 0.9, respectively, and a clinical success rate of 99%. A subsequent multicenter study by the same research group included 1300 patients (mean age 47.2 years, range 3-95 years) who underwent POEM for achalasia and showed consistent results, with a clinical success rate of 95.1% at 3 months and 94.7% at one year post-procedure[49] (Table 2).

Table 2 Characteristics of studies investigating peroral endoscopic myotomy.

Ref.	Year	Country	n	Population	Mean pre-POEM Eckardt score	Mean post-POEM Eckardt score
Bapaye et al[41]	2023	India	1	Children	NR	NR
Bi et al[28]	2023	China	48	Children	8	1.1
Caldaro et al[7]	2015	Italy	9	Children	7	0
Chen et al[50]	2014	China	27	Children	8.3	0.7
Choné et al[38]	2019	France	117	Children	7.5	0.9
Familiari et al[29]	2013	Italy	3	Children	5.3	0
Filser et al[85]	2015	Germany	1	Children	8	1
Hsu et al[5]	2023	Taiwan	10	Children	5.7	1.1
Kethman et al[23]	2017	United States	10	Children	7	2.4
Korrapati et al[99]	2018	India	15	Children	7	1
Li et al[87]	2014	China	9	Children	7	0.8
Liu et al[34]	2019	China	130	Children	7.4	0.7
Luvsandagva et al[53]	2024	Mongolia	12	Children	7	1
Mangiola et al[88]	2018	Italy	26	Children	7.2	0.3
Miao et al[33]	2017	China	21	Children	7.18	0.75
Nabi et al[75]	2017	India	502	Children & adults	7.1	1.1
Nabi et al[42]	2018	India	10	Children	6.7	0.3
Nabi et al[68]	2019	India	44	Children	6.86	1.03
Nabi et al[16]	2022	India	69	Children	7	1
Nabi et al[76]	2019	India	17	Children	6.88	NR
Nishimoto et al[86]	2018	Japan	13	Children	7.0	1.1
Petrosyan et al[4]	2016	United States	33	Children	9.7	0.9
Petrosyan et al[32]	2022	United States	37	Children	6.73	0.6
Peng et al[43]	2022	China	24	Children	7.67	0.67
Pop et al[24]	2022	Romania	7	Children	6.5	NR
Ramchandani et al[47]	2016	India	220	Children & adults	7.2	1.18
Ren et al[69]	2012	China	119	Children & adults	NR	NR
Rizzo et al[14]	2020	Europe	1	Children	12	0
Saez et al[89]	2020	Chile	5	Children	10	0.5
Samarakkody et al[90]	2022	New Zealand	4	Children	5.5	0
Samejima et al[54]	2023	Japan	10	Children	6.4	0.5
Shiwaku et al[48]	2016	Japan	100	Children & adults	5.9	0.8
Shiwaku et al[49]	2019	Japan	1300	Children & adults	6.1	1.1
Smirnov et al[91]	2018	Russia	1	Children	7	1
Stavropoulos et al[92]	2017	United States	10	Children	7.9	0.4
Tan et al[93]	2016	China	12	Children	6.9	0.7
Tang et al[51]	2015	China	5	Children	7.5	0.7
van Lennep et al[18]	2019	Netherlands	68	Children	NR	NR
Wood et al[52]	2020	United States	21	Children	7	1
Yamashita et al[94]	2016	Japan	1	Children	7	0
Yamashita et al[95]	2018	Japan	218	Children & adults	NR	NR
Yeung et al[96]	2017	China	1	Children	9	0
Zhang et al[67]	2016	China	1679	Children & adults	NR	NR

NR: Not reported.

A growing body of evidence from studies focusing exclusively on pediatric populations, has shown that POEM in children is as effective as it is in adults, considering a significant reduction between the pre- and post-POEM Eckardt scores[38,50]. A small retrospective study by Tang et al[51] in 2015, analyzed 5 pediatric patients that underwent POEM and reported a median operative time of 50 minutes (range: 40-90 minutes), a median submucosal tunnel length of 13 cm (range 7-15 cm), a median myotomy length of 8 cm (range: 6-11 cm), and successful treatment with Eckardt scores of less than 3 at a median follow-up of 18 months in all patients. These findings were consistent with a previous study by Familiari et al[29] in 2013 that showed decreased Eckardt scores (equal to zero) at 1 year follow up after POEM compared to a score of 5.3 at baseline. These results were further supported by a long-term single center study in 2018 by Miao et al[33] who investigated POEM in a cohort of 21 children and reported an average duration of 40 min, a significant decrease of 7 points between pre-POEM and post-POEM scores, and a success rate of 100%. More recent data from a multicenter international retrospective study showed clinical success (> 90%) of POEM in 117 patients who had an average baseline Eckardt score of 7.5 ± 2.0 compared to 0.9 ± 1.2 at a mean follow up of 545 days[38]. In 2020, Wood et al[52] conducted a single institution prospective cohort study in 21 pediatric patients who underwent POEM between 2014-2019 and reported a median Eckardt score of 1.0 ± 2.0 at 1-month follow-up, a score of 2.0 (range: 0-5) at 2.7 months follow-up (n = 18) and a score of 2.0 ± 1.4 at 1-year follow-up (n = 10), significantly improved from a pre-procedure score of 7.0 ± 2.0. In line with these findings, a study by Liu et al[34] that included 130 consecutive pediatric patients post-POEM, showed a mean preoperative Eckardt score and median LES pressure of 7.4 and 27.1 mmHg that significantly improved to 0.7 and 7.0 mmHg, respectively. In 2023, Bi et al[28] conducted a long-term follow-up (5.7 years) retrospective study in 34 pediatric patients after POEM and reported a clinical success rate of 97.2% and average post-POEM Eckardt score of 1.1 (range: 0-4) compared to baseline score of 8.0 (range: 4-11). The effectiveness of POEM in pediatric patients with achalasia was further demonstrated in the retrospective cohort study conducted by Luvsandagva et al[53] in 2024, that showed a notable post-procedure improvement of the IRP from a mean of 26.8 ± 5.4 mmHg pre-procedure to 10.8 ± 1.1 mmHg at 12 months (P < .001). Similarly, the Eckardt score decreased significantly to 1.0 ± 1.7 at 3 days post-procedure and remained stable at 1.0 ± 1.7 at one year post-procedure from a pre-procedure mean of 7.0 ± 1.0, reflecting enhanced patient quality of life and symptom alleviation. The outcomes of POEM in pediatric patients under 12 years of age (4 patients) were compared with those of patients aged between 13-18 years (6 patients) in the recent study by Samejima et al[54]. At three months after surgery, POEM demonstrated a 100% clinical success rate (Eckardt score < 3) in both groups and 50% of the patients in both groups experienced gastroesophageal reflux disease (GERD), which was treated with antacids in 2 patients of each group. The postoperative outcomes at 12 months were comparable and the clinical success rate remained at 100%.

Data from previous studies in purely pediatric populations were summarized by Lee et al[55] in a systematic review and meta-analysis of 12 studies involving 146 pediatric patients that showed a decrease in Eckardt score by 6.88 points (95%CI: 6.28-7.48, P < 0.001) and LES pressure by 20.73 mmHg (95%CI: 15.76-25.70, P < 0.001) post-POEM. The majority of the population experienced improvement or resolution of short-term (< 12 months - 96%) and long-term symptoms (> 12 months - 93%). An updated systematic review and meta-analysis by Nabi et al[3] published in 2022 identified 14 studies including 419 patients and showed similar results with a cumulative technical success rate of 97.1%, clinical success rate of 94.4%, and an average reduction in Eckardt scores of 6.71 points. Lastly, the most recent systematic review and meta-analysis published in 2024, reported mean pre- and post-procedure reductions of Eckardt scores and LES pressures of 4.39 and 3.63 mmHg, respectively, with a mean procedure time of 83.6 minutes[56].

Based on these findings, the outcomes of POEM between pediatric and adult populations are comparable. In terms of technical success rates pediatric studies demonstrate high efficacy (90%-100%) that are comparable to those reported in adults (85%-100%). However, the anatomical considerations present unique challenges in pediatric patients, and technical difficulties in the creation of the submucosal tunnel due to underlying fibrosis may necessitate the abortion of the procedure[57]. The smaller caliber and variable anatomy of pediatric esophagi may require greater endoscopic expertise. Centers with higher procedural volumes and more experienced endoscopists tend to have lower complication rates, with early data showing that efficiency is achieved at 40 cases while mastery is achieved at 60 cases[58]. Later data from an important and methodologically rigorous study by Liu et al[59] in 2018 placed that threshold higher and showed that the learning curve for POEM is approximately 100 cases in mixed adult/pediatric populations. Above that threshold, the risk of technical failure, adverse events, and clinical failure significantly decrease. In that study, POEM was performed by endoscopists with extensive experience in endoscopic mucosal dissection and in a high-volume center. Suspected risk factors for failure include pre-procedural (pre-treatment Eckardt score, prolonged disease duration, prior achalasia treatment, dilated esophagus and sigmoid-shaped esophagus, achalasia other than type II and cardiac muscle thickness), intra-procedural (location/Length of myotomy, experience of the operator, mucosal injury), and post-procedural factors (GERD)[60]. Younger age and higher pre-procedural Eckardt score, which includes weight loss as one of its components, have been identified as predictors of poor response to POEM in mixed populations[61,62]. Furthermore, delayed diagnosis and treatment, can lead to significant weight loss and worse nutritional status, which are good surrogates for disease severity[63]. However, data regarding the duration of symptoms are conflicting, with earlier data of mixed adult/pediatric population from 2018 by Li et al[64] supporting that long disease duration greater than 10 years is a risk factor for recurrence, and later data from 2023-2024 studies showing no association with symptom duration[65,66].

SAFETY: COMMON MINOR AND MAJOR ADVERSE EVENTS

The most common adverse events during POEM in pediatric patients include mucosal injury, capnoperitoneum, and retroperitoneal CO₂[60] (Table 3). Major adverse events in pediatric patients include conversion to surgery, hemodynamic instability, bleeding requiring transfusion, aspiration pneumonia, prolonged hospital stay, post-procedure intensive care unit stay, and hospital readmission[3,34,35]. Mild perioperative adverse events include insufflation-related adverse events, mucosal injuries, minor bleeding, and pain requiring analgesic medications[43]. The adverse events may occur several months after the procedure[67].

Table 3 Peroral endoscopic myotomy associated adverse events.

Ref.	Year	n	Mucosal perforation	Recurrent dysphagia	Wound infection	Pneumothorax	Pneumoperitoneum	Pneumomediastinum	Pneumonia	Subcutaneous emphysema	Fever	GERD	Reflux esophagitis	Leak within the tunnel/Dehiscence at entry site	Mucosotomy
Bapaye et al[41]	2023	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Bi et al[28]	2023	48	3	-	-	-	2	-	-	2	-	-	-	-	-
Caldaro et al[7]	2015	9	1	-	-	-	1	-	-	-	-	1	-	-	-
Chen et al[50]	2014	27	5	-	-	4	-	10	-	7	1	4	3	-	-
Choné et al[38]	2019	27	-	-	-	-	-	-	-	-	-	17	25	-	-
Familiari et al[29]	2013	3	-	-	-	-	-	-	-	-	-	-	-	-	-
Filser et al[85]	2015	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Hsu et al[5]	2023	10	-	-	-	-	6	2	-	2	2	-	-	-	-
Hu et al[97]	2023	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Inoue et al[31]	2010	10	-	-	-	-	-	-	-	-	-	-	1	-	-
Kethman et al[23]	2017	10	-	-	-	1	1	-	-	-	-	-	-	2	-
Li et al[87]	2014	9	-	-	-	-	-	-	-	1	-	-	1	-	-
Liu et al[34]	2019	130	-	-	-	1	-	-	-		-	30	17	-	-
Luvsandagva et al[53]	2024	12	-	2	-	-	-	-	-	2	-	3	3	-	-
Mangiola et al[88]	2018	26	-	-	-	-	4	-	1	4	-	-	-	-	-
Miao et al[33]	2017	21	-	-	-	-	1	1	-	1	1	6	2	-	-
Nabi et al[42]	2018	10	-	1	-	-	2	-	-	1	-	-	-	-	-
Nabi et al[76]	2019	17	-	-	-	-	1	-	-	-	-	-	9	-	-
Nabi et al[68]	2019	44	1	-	-	-	10	-	-	-	-	12	11	-	-
Nabi et al[16]	2022	69	-	-	-	-	-	-	-	-	-	29	14	-	-
Nabi et al[75]	2017	502	-	-	-	5	62	1	-	106	1	-	53	-	-
Nabi et al[98]	2017	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Nishimoto et al[86]	2018	13	-	-	-	1	-	-	-	-	-	1	-	1	-
Petrosyan et al[4]	2016	33	2	5	1	1	-	-	-	-	-	-	-	-	-
Petrosyan et al[32]	2022	37	-	-	-	9	10	2	-	-	-	3	-	-	5
Pop et al[24]	2022	4	-	-	-	-	2	1	-	-	-	-	-	-	-
Ramchandani et al[47]	2016	220	14	-	-	3	40	-	-	32	-	-	14	-	-
Ren et al[69]	2012	119	-	1	-	30	47	35	-	66	-	-	-	-	-
Rizzo et al[14]	2020	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Saez et al[89]	2020	5	-	-	-	-	-	-	-	-	-	-	-	-	-
Samarakkody et al[90]	2022	4	-	1	-	-	1	-	-	1	-	1	-	-	-
Samejima et al[54]	2023	10	-	-	-	-	-	-	-	-	-	-	1	-	-
Shiwaku et al[48]	2016	100	-	-	-	1	11	1	-	-	-	-	-	1	-
Shiwaku et al[49]	2019	1300	5	-	-	-	-	-	-	-	-	173	1176	-	-
Smirnov et al[91]	2018	1	-	-	-	-	-	-	-	-	-	-	-	1	-
Stavropoulos et al[92]	2017	10	3	-	-	-	-	-	-	-	-	-	2	-	-
Tan et al[93]	2016	12	-	-	-	-	-	-	-	1	-	-	2	-	-
Tang et al[51]	2015	5	-	-	-	-	-	-	-	-	-	-	-	-	-
van Lennep et al[18]	2019	68	-	-	-	-	-	-	-	-	-	-	-	-	-
Wood et al[52]	2020	21	-	-	-	-	1	-	-	-	1	-	-	-	-
Yamashita et al[94]	2016	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Yeung et al[96]	2017	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Zhang et al[67]	2016	1679	-	-	-	25	-	-	-	-	-	-	-	-	-

GERD: Gastroesophageal reflux disease.

Rates of adverse events after POEM in pediatric patients vary widely across different studies. In 2016, Zhang et al[67] included 77 pediatric patients in their 5-year analysis, and reported 1 case of pneumothorax, no tunnel orifice dehiscence, no hydrothorax, and a total of 3 major adverse events (3.9%). In 2019 Nabi et al[68] conducted a retrospective study in 44 children post- POEM and found a 27.9% incidence of intra-operative adverse events, including retroperitoneal CO₂, intraoperative capnoperitoneum requiring drainage, and intra-operative mucosal injury. Subsequently, in 2022, Petrosyan et al[32] reported a series of 37 children treated with POEM for achalasia that were followed at a mean of 22.6 months. Intraoperative complications occurred in 16 patients (43.2%), including mucosotomies outside of the site of POEM (13.5%), pneumomediastinum (5.4%), pneumothorax (24.3%), pneumoperitoneum (27%), failed POEM (2.7%). Postoperative complications included GERD (8.1%) and recurrent dysphagia (13.5%). In the 2023 retrospective study of Bi et al[28], that included 48 pediatric patients, the reported overall complications rate was lower (14.6%) compared to the other studies, and included mucosal injury (6.2%), pneumoperitoneum (4.2%), and subcutaneous emphysema (4.2%).

Higher rates of complications have been observed with the use of air as the insufflating agent in mixed pediatric/adult populations[69]. Another possible explanation for the variable incidence and higher rates of adverse events in some studies is that endoscopes used in POEM are designed for adults, and are relatively large for pediatric patients, thereby increasing the risk of mucosal injury. In addition, due to the smaller body size of pediatric patients, performing the procedure under adult conditions may be associated with excessive insufflation and severe emphysema. Therefore, further development of thinner endoscopes for therapeutic use and improvements in the CO₂ insufflation system (such as transitioning from the current volume control method to a pressure control system similar to that used in laparoscopy) should be considered. Due to the anatomic difference between the child and adult esophagus, POEM in pediatric achalasia is performed with shorter length of myotomy. In addition, the thin esophageal wall of children requires caution during the establishment of the submucosal tunnel[2]. Most pediatric POEM procedures have traditionally employed myotomy lengths between 7.0-11.0 cm and submucosal tunnel length between 10.0-12.6 cm[2]. Recent studies have explored the feasibility of shorter myotomies in mixed populations and have shown comparable efficacy and safety between short (2.76-5 cm) and standard myotomy (6.9-10 cm)[70]. A shorter myotomy length may reduce the rate of reflux esophagitis and the risk of blown out myotomy, which is a pseudodiverticulum that gradually enlarges and affects esophageal emptying[71].

POEM VS ALTERNATIVE TREATMENTS IN CHILDREN

Pediatric literature comparing POEM with other treatments is limited. In adults, according to the ACG Clinical Guidelines[72] for the management of achalasia, PD, LHM and POEM are effective therapies with comparable outcomes in achalasia type I and II, while POEM would be a better option in achalasia type III. Pharmacological treatment options, such as calcium channel blockers or endoscopic botulinum toxin injections in the LES are rarely used in the pediatric population because of their short-term effectiveness and potential side effects of calcium-channel blockers, such as headache and dizziness[73]. Despite the limited evidence, POEM has shown promising results compared to PD and LHM in children[74] (Table 4). In the study by Nabi et al[75] in a mixed population of adults and children in 2018, outcomes of POEM as a first treatment were compared with outcomes of POEM as treatment for prior failure. They showed a significantly prolonged operative time (74.9 minutes vs 67.0 minutes, P = 0.002) in the group undergoing POEM as a treatment for failure, but success rates (92.4% vs 92.5%, P = 0.95) and adverse events associated with gas insufflation and mucosotomy were comparable between the groups. In 2019, the same group of authors evaluated POEM in a retrospective cohort of 53 pediatric patients, including 6 patients with prior PD, one with prior LHM, and one with both prior LHM and PD, and showed no difference in success rates (77.8% vs 100%, P = 0.471) and adverse events (33.3% vs 25%, P = 1.0) between “naïve” POEM and POEM for prior failure[76]. Based on the current evidence, the SAGES guidelines suggest that POEM and LHM are both appropriate choices in pediatric patients with type I or type II achalasia considering a shared-decision making between patients and providers, while POEM is recommended over LHM in type III pediatric achalasia based on expert experience[77].

Table 4 Comparison of peroral endoscopic myotomy with other treatments.

Treatment	Peroral endoscopic myotomy	Laparoscopic heller myotomy	Pneumatic dilation
Complications (%)	> 20	7-30	0-10
Success rate (%)	96.2-100	35-100	0-100
Need for further surgery (%)	< 0.1	3-42	17-100

POEM and PD in pediatric patients have similar effectiveness as in adult patients, but in pediatric patients POEM may be associated with a higher rate of clinical success compared to PD. The main advantage of PD is its low cost and that it can be repeated if needed before or after myotomy[78]. Pooled data from a systematic review conducted in 2020 by Goneidy et al[74], who summarized 33 studies including 742 children treated for achalasia, showed that patients who underwent POEM instead of PD had more prior treatments (21.3% vs 9.1%), more complications (24.4% vs 5.0%), fewer comorbidities (0.01% vs 22.9%) and lower need for further surgical investigation (0.01% vs 62.3%). The success rate of POEM was 99.3% and the success rate of PD was 44.9%. POEM can be performed without technical difficulties in patients who previously had undergone PD, even in patients who had previously undergone PD twice[79]. Age should be taken into account, considering that age younger than 7 years is a negative predictive factor for PD success[78].

In both adults and pediatric patients, POEM and LHM yield comparable outcomes and complications. In adults, POEM and LHM have shown comparable results[80-82], but a meta-analysis by Marano et al[83], that included 196 patients that underwent POEM and 290 patient after LHM, showed that POEM resulted in a significantly shorter length of hospital stay and reduced symptomatic GERD. In pediatric patients, the retrospective study by Caldaro et al[7], that included 18 pediatric patients who underwent LHM (n = 9) or POEM (n = 9) between 2009 to 2013, found that POEM was associated with shorter procedure time and longer myotomy compared to LHM. According to the systematic review by Goneidy et al[74], POEM had a higher clinical success rate (99.3%) compared to LHM (77.9%), and patients with LHM had undergone more prior treatments (30%) than patients with POEM (21.3%), and more frequently had comorbidities (18.8% vs 0.01%) and needed further surgical intervention (10.9% vs 0.01%). Nevertheless, POEM was associated with an approximately two-fold higher risk of complications (24.4%) compared to LHM (12.8%). The current evidence indicates that POEM is superior to LHM in terms of efficacy at the cost of a higher complication rate.

CONCLUSION

Achalasia in children is a rare condition, and its management is a significant challenge. Based on the current literature, POEM has the potential to become the first-line treatment for achalasia in pediatric patients in the future. POEM appears to have the highest success rate, but it has been associated with higher complication rates compared to LHM and PD. POEM is a relatively new technique that has been applied to pediatric patients only since 2008, and the existing data in the literature are promising but not sufficient to definitively favor one therapeutic option over another. Identifying and individualizing the most appropriate treatment for achalasia in children through shared decision making between providers and patients/parents is crucial, considering a long life-expectancy, and the effect that achalasia exerts on their quality of life. The need for large, prospective trials involving children with achalasia is of utmost importance. Mussies et al[84] have proposed their protocol for a prospective international multicenter randomized controlled clinical trial and the results of this study are highly anticipated.