Results of Laparoscopic Heller's Myotomy for Achalasia in Children: A Systematic Review of the Literature

Abstract

Introduction:

Achalasia is a rare disorder in children who are commonly treated by laparoscopic Heller's myotomy (LHM). However, there are no large studies evaluating the results of LHM in the pediatric population, and the need of a concomitant fundoplication remains unclear. The aim of the study is to appraise the results of LHM based on a systematic literature review.

Materials and Methods:

MEDLINE search of the English literature was performed for “achalasia,” “children,” “laparoscopy,” “Heller,” “myotomy,” and “cardiomyotomy.” Frequency of postoperative symptoms was grouped to calculate the percentage of patients with symptoms improvement. Incidence of postoperative gastro-esophageal reflux (GER) and dysphagia between patients with and without fundoplication at the time of LHM was compared by Fisher's Exact Test. P < .05 was regarded as significant.

Results:

Twenty-one studies were analyzed (331 children, 1–19 years). All studies were retrospective case-series reviews. Intraoperative complications occurred in 33 patients (10%), with esophageal perforations in 31 (9%), and conversion to open procedure in 9 (2.7%). Fundoplication was performed in 271 (82%): Dor (n = 205, 76%), Toupet (n = 49, 18%), Thal (n = 13, 4.5%), and Nissen (n = 4, 1.5%). Incidence of postoperative GER and dysphagia was similar between children with and without fundoplication (P = 1). Forty-nine (15%) required re-intervention: pneumatic dilatations (n = 30, 9%), redo-surgery (n = 23, 7%), botox injection (n = 1, 0.3%), and medical therapy (n = 5, 1.5%).

Discussion:

LHM for achalasia is effective in 85% of children. Revision surgery is required in 7%. There is no difference in incidence of GER and dysphagia between patients with and without fundoplication. Routine use of an additional fundoplication might not be justified.

Introduction

Achalasia is a primary functional motor disorder of the lower esophageal sphincter (LES) with an incidence of 0.1–0.18/10⁵ per year in children under 16 years of age in the United Kingdom.^1,2 It is more common in adults with an incidence up to 1.63/10⁵, with only 5% of cases involving patients younger than 15 years of age.^3,4 It affects boys more than girls (1.25:1) and is rare during infancy.^1,5 The disease is characterized by increased LES resting pressures, absent esophageal body contractions, and impaired LES relaxation during swallowing but the exact etiology is unknown. It can be associated with trisomy 21, congenital hypoventilation syndrome, glucocorticoid insufficiency, eosinophilic esophagitis, familial dysautonomia, Chagas' disease, and Allgrove's syndrome (triple A syndrome) that consists of achalasia, alacrima, and adrenocorticotropic hormone insensitivity.⁶

Common symptoms in children include dysphagia, odynophagia, regurgitations after meals, and weight loss. The diagnosis is usually confirmed by a combination of investigations, including barium meal, esophageal manometry, and upper gastrointestinal endoscopy.

The treatment aims at reducing the resting LES pressure by either medical or surgical means. A variety of treatments have been described in both adults and children. The use of calcium channel blockers (nifedipine) has been investigated more extensively in adults. Nifedipine shows a significant decrease in frequency of dysphagia and resting LES pressure.^7,8 However, symptoms of dysphagia, regurgitation, and nocturnal cough persist despite the reduction in LES pressure and nifedipine has not been recommended as a valid treatment option.⁹

Furthermore, Nifedipine use in children is not licensed in the United Kingdom for the possible numerous serious side effects, including hypotension, tachycardia, dyspnea, and syncope, making it not a valid long-term option.¹⁰

In adults, an endoscopic injection of botulinum toxin might have an initial favorable response; nonetheless, it often requires multiple injections for durable relief of symptoms, with the majority of patients remaining symptomatic and, ultimately, requiring surgery.¹¹

Other treatment options include esophageal dilatations with bougies or pneumatic balloon dilators, and results are generally more durable than botulinum toxin injections. There are scanty studies in children, with 60%–83% having a favorable response although 20% of patients require repeat treatment and most of them will eventually necessitate esophageal myotomy.^12–14 Peroral endoscopic myotomy (POEM) is a promising technique in adults,^15,16 but the experience in children is limited.^17–19

The esophageal myotomy described by Ernest Heller in 1913²⁰ and modified by De Brune Groenveldt in 1918²¹ is currently performed in many centers for definitive symptoms control in both adults²² and children.¹⁰ For many years, this procedure has been performed by an open approach, either via a thoracotomy or laparotomy. In 1991, Shimi and colleagues²³ reported the first successful laparoscopic Heller's myotomy (LHM) in adults; in 1996, Holcomb and colleagues²⁴ first reported on two children with achalasia who were successfully treated by LHM. Since then, more authors have reported favorable results, with a minimally invasive approach to this disease in children led by the recognition that laparoscopic surgery is generally associated with reduced postoperative morbidity, pain, and hospital length of stay.²⁵ The role of a concomitant antireflux procedure at the time of the esophageal myotomy remains controversial. A recent systematic review and meta-analysis²² has summarized the results of the endoscopic and surgical treatments for achalasia in adults; the study concluded that the LHM with added partial fundoplication provides superior and longest-lasting symptom relief with low morbidity compared with other types of treatments. The experience of LHM in children is limited and to date, there are no large studies that have investigated the results of this technique and clarified whether an additional antireflux procedure is needed at the same time. The aim of this article is to summarize the results of the LHM for esophageal achalasia in children based on the results of a systematic literature review of articles published in the past 20 years.

Materials and Methods

An electronic MEDLINE literature search on LHM for esophageal achalasia in children published between 1996 and 2016 was performed in August 2016. Keywords searched for included: “achalasia,” “children,” “laparoscopy,” “Heller,” “myotomy,” and “cardiomyotomy.” Only articles in the English language were considered. Publications of case reports, abstracts only, letters, and comments were excluded. Studies containing children and adults for whom no clear distinction was possible were excluded. A full text copy of each article was obtained for review. References within the selected articles were checked to complement the electronic search for additional relevant articles. Selected studies could be of any design. When different articles reporting on overlapping populations were identified, the most recent article with the largest study population was selected for review.

Each article was searched to extract data related to the research design used, population studied, treatment described, and outcome measures. The data collected were recorded in a database (Microsoft Excel 2013; Microsoft Corporation^®). Outcome measures searched for in the articles included patients' demographics (age and weight at surgery, gender), preoperative investigations and therapy, intra- and postoperative complications, addition of antireflux surgery and type, conversion to open procedure, length of hospital stay, length of follow-up, frequency of improvement or complete relief of symptoms, need for repeated or additional therapy/surgery, and prevalence of reported post-treatment gastro-esophageal reflux (GER). Reported frequency of pre- and post-operative symptoms was grouped together to calculate the percentage of patients with symptom improvement. A comparison of incidence of postoperative GER and dysphagia between patients with and without fundoplication at the time of LHM was performed by Fisher's Exact Test by using the program GraphPad Prism 6 (©1992–2014 GraphPad Sowftware, Inc.).

Results

Overall, 75 studies were identified and screened. There were 26 studies suitable for consideration for further analysis. All studies were retrospective reviews of case series (level 4 evidence for therapeutic studies²⁶) with no prospective study. Five studies were later excluded: Two studies^3,27 contained patients reported in subsequent studies; one study²⁸ was excluded, as no distinction was possible between patients who had open Heller's myotomy and LHM (14 patients); and two studies^29,30 were excluded, as children and adults were grouped together, and no distinction between the two groups was possible. The remaining 21 studies^{10,24,31–49} were reviewed and are the subject of this article.

Main findings

Main findings are summarized in Table 1. There were a total of 331 patients between the 21 studies considered who underwent LHM; male-to-female ratio was 1.2:1. The largest studies by Esposito and colleagues³⁶ and Petrosyan and colleagues⁴⁵ included 31 patients; one study²⁴ reported on two patients only. Age at surgery was available for all studies; weight at surgery was available only for 4 (19%) studies; and duration of symptoms was available only for 10 (47%) studies.

Table 1.

Demographics and Main Findings

Study	Year	No. of patients	Gender M:F	Age at surgery (years)	Weight (kg)	Symptoms duration (years)	Associated anomalies (%)	Operating time (minutes)	Intraoperative complications	Conversion to open procedure	Length of stay (days)	Follow-up (months)	Postoperative dysphagia
Petrosyan et al.⁴⁵	2016	33^a [31 LHM]	13:20^a	12.9 (5–18)^a	N/A	2.8 (1–11)^a	N/A	113 (45–352)	2 perforations	—	1.9 (1–6)^a	30.9 (7–84)^a	5 (16)
Zagory et al.⁴⁹	2016	23^b [19^c LHM]	14:9^b	11.6 (0–17)^b	N/A	18 (1–89)^b	9 (39)^b	N/A	6 perforations (5^d)	2 (10.5)	6.5 (1–40)	24 (1–124)^b	5 (26)
Caldaro et al.³³	2015	9	6:3	10.8 (2–17)	N/A	N/A	1 (11)	149 ± 33.8	1 perforation	—	6 (3–18)	31 (13–63)	2 (22)
Pachl et al.⁴²	2014	28	13:15	13 (3.2–17.4)	N/A	N/A	2 (7)	N/A	1 perforation	—	3 (1–8)	10 (0–60)	8 (28)
Franklin et al.¹⁰	2014	24	11:13	12.9 (5–18)	N/A	2.8 (1–11)	5 (21)	124 (45–213)	2 perforations	—	2.7 (1–6)	4 (4–24)	3 (12.5)
Alkhatrawi et al.³¹	2013	8	4:4	4.3 (1–13)	N/A	N/A	N/A	44 (no range)	—	—	2 (2–3)	40.3 (6–62)	—
Esposito et al.³⁶	2013	31	18:13	8.4 (5–14.9)	N/A	N/A	N/A	120 (90–250)	3 perforations^d	—	4 (3–8)	(9–156)^e	5 (16)
Lee et al.³⁹	2010	34 [7 LHM]	21:13^f	13 ± 6^f	N/A	7.2 (1–72)	Gastrointestinal (32)^f	N/A	—	—	N/A	7.3 (0.5–186)^g	N/A
							Neurologic (24)^f
							Pulmonary (24)^f
							Cardiac (6)^f
Corda et al.³⁴	2010	20	13:7	12 (5–15)	38 (15–53)	2.4 (1.5–5)	N/A	90 (60–160)	2 perforations	4 (20)	3 (1–5)	60 (8–114)	5 (25)
									1 bleeding
									1 technical
Tannuri et al.⁴⁷	2010	15	7:8	12 (9–17)	N/A	2.5 (0.3–7)	3 (20)	190 (150–260)	—	1 (7)	2.5 (1–4)	32.3 (2–8)	2 (14)
Askegard-Giesmann et al.³²	2009	26	15:11	15 (4–18)	N/A	N/A	N/A	N/A	2 perforations^h	—	3.5 (1–17)	20.4 (0–74.5)	7 (27)
									1 aspiration
Jafri et al.³⁸	2008	19 [11 LHM]	1.4:1 (ratio)^f	11 (6.5–19)^f	N/A	N/A	N/A	212.3 ± 48	2 perforations	—	N/A	3.5 ± 0.6	4 (36)
								225 ± 25.4
Paidas et al.⁴³	2007	14	8:6	17 (11–19)	N/A	5 ± 3.3	3 (21)	N/A	1 perforation	—	3 ± 2.9	35 ± 27.9	N/A
Garzi et al.³⁷	2007	12	8:4	10.5 (3–14)	N/A	N/A	6 (50)	120 (90–180)	1 perforation	—	(5–8)^e	(18–60)^e	3 (25)
Mattioli et al.⁴⁰	2003	20	14:6	10 (5–14)	45 (25–72)	N/A	N/A	125 (90–180)	1 perforation	—	3 (3–4)	45 (6–102)	5 (25)
									1 bleeding
Patti et al.⁴⁴	2001	13	6:7	15 (6–17)	N/A	24 (no range)	N/A	144 ± 35	—	—	1.4 ± 1.1	18 (no range)	—
Rothenberg et al.⁴⁶	2001	9 [5 LHM]	N/A	12 (5–17)ⁱ	45 (23–78)ⁱ	(0.5–2)^e,i	N/A	62 (45–120)	1 perforation	—	1	N/A	N/A
Mehra et al.⁴¹	2001	22 [18 LHM]	12:10ⁱ	11.3 (5.3–18.5)ⁱ	N/A	N/A	N/A	N/A	2 perforations	2 (11)	2.7 + 0.3	17 (1–54)ⁱ	N/A
Esposito et al.³⁵	2000	10	5:5	(2–13)^e	(13–39)^e	N/A	N/A	120 (90–150)	2 perforations	—	4 (3–41)	(6–72)^e	1 (10)
Waldhausen et al.⁴⁸	1999	8	3:5	14.5 (11–17)	N/A	N/A	N/A	186 (110–385)	—	—	2 (2–3)	13 (1–24)	1 (12.5)
Holcomb et al.²⁴	1996	2	1:1	12 and 13	N/A	0.3 and 0.5	—	110 and 130	—	—	1	17 and 18	—

Data are reported as number of case (%), median (range), mean ± SD, or mean ± SEM.

Including 2 patients who had peroral endoscopic myotomy.

Including patients who underwent previous esophageal dilatations.

Ten patients had previous esophageal dilatations.

Patients with previous treatment before LHM.

Range only reported.

Including patients who did not undergo LHM.

Including patients who had open and thoracoscopic surgery.

One perforation during redo-surgery.

Including patients who had thoracoscopic Heller's myotomy.

LHM, laparoscopic Heller's myotomy; N/A, data not available.

Incidence of associated anomalies and operating time was reported in 8 (38%) and 16 (76%) studies, respectively. Intraoperative complications were reported in 33 (10%) patients; perforations of the esophageal mucosa occurred in 31 (9%) patients. Conversion to open procedure was required in 9 (2.7%) patients. Data regarding length of hospital stay and postoperative follow-up were available for 19 (90%) studies. Overall incidence of postoperative dysphagia, available in 17 studies, was 19% (56 out of 287 patients), with no difference in the incidence between patients with and without fundoplication (45/229 versus 11/58, P = 1).

Preoperative symptoms

Information regarding preoperative symptoms was available in 13 (62%) studies; eight studies did not provide any details regarding the incidence and type of preoperative symptoms (Table 2). Dysphagia was the most common symptom reported in 88% of cases; emesis and weight loss were present in 52% and 45%, respectively. Other symptoms included chest pain (23%), regurgitations (23%), respiratory problems (10%), and odynophagia (3%).

Table 2.

Preoperative Symptoms and Treatments

	Petrosyan et al. ⁴⁵	Zagory et al. ⁴⁹	Caldaro et al. ³³	Pachl et al. ⁴²	Franklin et al. ¹⁰	Alkhatrawi et al. ³¹	Esposito et al. ³⁶	Lee et al. ³⁹	Corda et al. ³⁴	Tannuri et al. ⁴⁷	Askegard-Giesmann et al. ³²	Jafri et al. ³⁸	Paidas et al. ⁴³	Garzi et al. ³⁷	Mattioli et al. ⁴⁰	Patti et al. ⁴⁴	Rothenberg et al. ⁴⁶	Mehra et al. ⁴¹	Esposito et al. ³⁵	Waldhausen et al. ⁴⁸	Holcomb et al. ²⁴
No. of patients	33 [31 LHM]	23 [19 LHM]	9	28	24	8	31	34 [7 LHM]	20	15	26	19 [11 LHM]	14	12	20	13	5	22 [18 LHM]	10	8	2
Preoperative symptoms
Dysphagia	28^a (85)	16^b (69)	N/A	N/A	20 (83)	8 (100)	N/A	29 (85)^c	N/A	10 (66)	26 (100)	19 (100)^c	14 (100)	12 (100)	20 (100)	N/A	N/A	N/A	N/A	8 (100)	1 (50)
Emesis	17^a (52)	16^b (69)	N/A	N/A	14 (58)	5 (62)	N/A	20 (59)^c	N/A	—	>50%	19 (100)^c	53.3%	12 (100)	—	N/A	N/A	N/A	N/A	—	1 (50)
Weight loss	13^a (39)	20^b (87)	N/A	N/A	11 (46)	8 (100)	N/A	15 (44)^c	N/A	11 (73)	—	12 (63)^c	—	12 (100)	—	N/A	N/A	N/A	N/A	4 (50)	2 (100)
Chest pain	19^a (58)	—	N/A	N/A	10 (42)	—	N/A	13 (38)^c	N/A	1 (6)	—	5 (26)^c	60%	—	—	N/A	N/A	N/A	N/A	—	—
Regurgitation	8^a (24)	—	N/A	N/A	4 (17)	8 (100)	N/A	12 (34)^c	N/A	8 (53)	—	1 (5)^c	46.2%	—	—	N/A	N/A	N/A	N/A	8 (100)	—
Respiratory	—	—	N/A	N/A	—	2 (25)	N/A	8 (24)^c	N/A	2 (13)	—	—	—	7 (58)	5 (100)	N/A	N/A	N/A	N/A	—	—
Odynophagia	6^a (18)	—	N/A	N/A	2 (8)	—	N/A	—	N/A	—	—	—	—	—	—	N/A	N/A	N/A	N/A	—	—
Premyotomy treatment
Pneumatic dilatation	—	10 (52)	3 (33)	9 (32)	4 (17)^d	—	1 (3)	11 (32)^c	6 (20)	5 (66)	14 (54)	14 (73.7)^c,d	2 (14)	N/A	—	2 (16)	5 (100)	12 (54)^e	—	5 (62.5)	—
Nifedipine	—	—	1 (11)	1 (3.5)	2 (8)	—	6 (19)	4 (11)^c	—	—	—	—	—	N/A	—	—	—	2 (9)^e	6 (60)	—	—
Botulin injection	—	—	—	1 (3.5)	—	—	1 (3)	1 (3)^c	—	—	6 (23)	2 (10.5)^c	1 (7)	N/A	—	1 (8)	—	7 (58)^e	—	2 (25)	—

Data are reported as number of case (%).

Including 2 patients who had peroral endoscopic myotomy.

Including patients who underwent esophageal dilatations.

Including patients who did not undergo surgery.

One esophageal perforation.

Including patients who underwent thoracoscopic Heller's myotomy.

LHM, laparoscopic Heller's myotomy; N/A, data not available.

Preoperative investigations and treatment

Preoperative investigations are summarized in Table 3. Patients were investigated with a combination of techniques. A barium meal was the most commonly performed investigation in 97% of patients; esophageal manometry was performed in 76% of patients; endoscopy, in 61% of patients; and pH-study, in 9% of patients. One center only performed the pH-study in all patients.⁴⁰ Information regarding the use of alternative type of treatments before LHM was reported in 20 studies (Table 2). Overall, 44% of patients underwent a combination of preoperative treatments before LHM: pneumatic dilatation, 32%; oral nifedipine and botulinum toxin injection, 7% respectively. Two (2%) patients out of the 103 who received pneumatic dilatations had an esophageal perforation that was managed by video-assisted thoracoscopic surgery (VATS) in one case¹⁰ and treated with antibiotics and bowel rest and resolved without surgical intervention in another one.³⁸

Table 3.

Preoperative Investigations

Study	Barium meal	Esophageal manometry	Endoscopy	pH-study
Petrosyan et al.⁴⁵	31 (100)	(33)	(33)	—
Zagory et al.⁴⁹	19 (100)	19 (100)	19 (100)	—
Caldaro et al.³³	9 (100)	9 (100)	9 (100)	—
Pachl et al.⁴²	28 (100)	25 (89)	—	—
Franklin et al.¹⁰	N/A	9 (38)	N/A	—
Alkhatrawi et al.³¹	8 (100)	—	8 (100)	—
Esposito et al.³⁶	31 (100)	31 (100)	31 (100)	—
Lee et al.³⁹	N/A	N/A	N/A	N/A
Corda et al.³⁴	N/A	20 (100)	20 (100)	—
Tannuri et al.⁴⁷	15 (100)	N/A	N/A	N/A
Askegard-Giesmann et al.³²	26 (100)	26 (100)	N/A	—
Jafri et al.³⁸	11 (100)	11 (100)	11 (100)	—
Paidas et al.⁴³	11 (78)	8 (57)	4 (30)	—
Garzi et al.³⁷	9 (75)	10 (83)	9 (75)	1 (8)
Mattioli et al.⁴⁰	20 (100)	20 (100)	20 (100)	20 (100)
Patti et al.⁴⁴	13 (100)	13 (100)	13 (100)	2 (16)
Rothenberg et al.⁴⁶	5 (100)	3 (33)	—	—
Mehra et al.⁴¹	21 (95)^a	16 (72)^a	—	—
Esposito et al.³⁵	10 (100)	10 (100)	10 (100)	6 (60)
Waldhausen et al.⁴⁸	8 (100)	8 (100)	—	—
Holcomb et al.²⁴	2 (100)	1 (50	—	—

Data are reported as number of case (%).

Including patients who undergo thoracoscopic Heller's myotomy.

N/A, no data available.

GER and fundoplication

Information about the presence of preoperative GER was available in 8 (38%) studies and reported in 9 (3%) patients; one study³² reported an incidence of GER >50%. No information is available as to whether the GER was diagnosed clinically, on pH-study or barium meal.

A concomitant fundoplication was performed in 18 (85%) studies for a total of 271 (82%) patients (Table 4). The Dor fundoplication was performed in 205 (76%) patients, Toupet fundoplication in 49 (18%), Thal fundoplication in 13 (4.5%), and Nissen fundoplication in 4 (1.5%). Postoperative reflux was reported in 8 (2.5%) patients; 7 (2.5%) patients had received a fundoplication at the time of the LHM. One (3%) patient out of the 60 who did not receive a concomitant fundoplication at the time of LHM presented with postoperative GER (P = 1.0), RR 1.5 (95% CI 0.19–12.3).

Table 4.

Incidence of Preoperative and Postoperative Gastro-Esophageal Reflux and Type of Fundoplication

Study	Preoperative GER	Any fundoplication	Type of fundoplication	Postoperative GER
Petrosyan et al.⁴⁵	N/A	27 (87)	Dor 25 (92)	N/A
			Thal 2 (8)
Zagory et al.⁴⁹	N/A	18 (95)	Dor 10 (52)	N/A
			Toupet 5 (26)
			Thal 3 (16)
Caldaro et al.³³	N/A	9 (100)	Dor 9 (100)	1 (11)^a
Pachl et al.⁴²	N/A	10 (35)	Dor 9 (32)	3^a + 1 (14)
			Nissen 1 (3.5)
Franklin et al.¹⁰	N/A	21 (87.5)	Dor: 19 (79.2)	—
			Thal: 2 (8.3)
Alkhatrawi et al.³¹	—	—	—	—
Esposito et al.³⁶	N/A	31 (100)	Dor 31 (100)	—
Lee et al.³⁹	4 (12)^b	5 (71)	Dor 4 (57)	N/A
			Nissen 1 (14)
Corda et al.³⁴	N/A	—	—	—
Tannuri et al.⁴⁷	N/A	15 (100)	Dor 15 (100)	—
Askegard-Giesmann et al.³²	>50%	25 (96)	Dor 2 (8)	1 (4)^a
			Toupet 23 (88)
Jafri et al.³⁸	1 (5)^b	11 (100)	Dor 2 (17)	1 (9)^a
			Toupet 9 (75)
Paidas et al.⁴³	N/A	14 (100)	Dor 14 (100)	N/A
Garzi et al.³⁷	3 (25)	12 (100)	Dor: 6 (50)	—
			Thal: 6 (50)
Mattioli et al.⁴⁰	—	20 (100)	Dor 20 (100)	—
Patti et al.⁴⁴	—	12 (92)	Dor 12 (92)	—
Rothenberg et al.⁴⁶	N/A	5 (100)	Dor 4 (80)	—
			Toupet 1 (20)
Mehra et al.⁴¹	N/A	18 (100)	Dor 8 (44)	—
			Toupet 8 (44)
			2 Nissen (12)
Esposito et al.³⁵	N/A	10 (100)	Dor 7 (70)	—
			Toupet 3 (30)
Waldhausen et al.⁴⁸	N/A	8 (100)	Dor 8 (100)	1 (12.5)^a
Holcomb et al.²⁴	1 (50)	—	—	—

Data are reported as number of case (%).

Patients had laparoscopic myotomy plus fundoplication.

Including patients who did not undergo surgery.

GER, gastro-esophageal reflux; N/A, data not available.

Failure and re-intervention

Overall, 49 (15%) patients required re-intervention after LHM, either as a single procedure alone or in combination with other procedures (Table 5). Pneumatic dilatations were performed in 30 (9%) patients, botulinum toxin injection in 1 (0.3%), and other management was required in 5 (1.5%). Redo-surgery was required in 23 (7%) patients: One patient underwent two redo-LHM³⁴; in 2 patients, redo-surgery was required for postoperative perforation that was not recognized at the time of surgery.^24,46

Table 5.

Re-Intervention After Laparoscopic Heller's Myotomy

Study	Pneumatic dilatations	Botulin injection	Other management	Redo-surgery	Any procedure
Petrosyan et al.⁴⁵	3/31 (10)	—	—	2/31 (6)	5/31 (16)
Zagory et al.⁴⁹	4/19 (21)	—	—	2/19 (10)	6/19 (31)
Caldaro et al.³³	2/9 (22)	—	—	—	2/9 (22)
Pachl et al.⁴²	7/28 (25)	—	—	5/28 (18)	8/28 (28)
Franklin et al.¹⁰	2/24 (8)	—	—	1/24 (4)	3/24 (12.5)
Alkhatrawi et al.³¹	—	—	—	—	—
Esposito et al.³⁶	2/31 (6)	—	—	1/31 (3)	3/31 (9.6)
Lee et al.³⁹	N/A	—	N/A	N/A	N/A
Corda et al.³⁴	2/20 (10)	—	3/20 (15); prokinetics	3/20 (15) (1 patient had 2 redos)	5/20 (30)
Tannuri et al.⁴⁷	—	1 (7)	—	—	1 (7)
Askegard-Giesmann et al.³²	3/26 (11)	—	2/26 (8); 1 antireflux, 1 unknown	3/26 (11)	8/26 (30)
Jafri et al.³⁸	3/11 (27)	—	—	1/11 (9)	4/11 (36)
Paidas et al.⁴³	—	—	—	2/14 (15)	—
Garzi et al.³⁷	—	—	—	1/12 (8)	1/12 (8)
Mattioli et al.⁴⁰	1/20 (5)	—	—	—	1/20 (5)
Patti et al.⁴⁴	—	—	—	—	—
Rothenberg et al.⁴⁶	—	—	—	1 (20) (postoperative perforation)	—
Mehra et al.⁴¹	1 (5)	—	—	—	—
Esposito et al.³⁵	—	—	—	2/10 (20) (1 postoperative perforation)	2/10 (20)
Waldhausen et al.⁴⁸	—	—	—	—	—
Holcomb et al.²⁴	—	—	—	—	—

Data are reported as number of case (%).

N/A, data not available.

Discussion

LHM for achalasia was originally reported in adults by Shimi and colleagues²³ in 1991. In 1996, Holcomb and colleagues²⁴ first reported on 2 children with achalasia who were successfully treated by LHM, and, subsequently, a number of other authors have reported their experience in the pediatric population. Although a variety of treatment options are available, to date the procedure remains the definitive treatment of choice in many pediatric centers. Nonetheless, since achalasia is a rare disorder in children, there are no large studies reporting the results of LHM in this age group. This systematic review identified 21 studies for a total of 331 children treated for achalasia with LHM. This number is somewhat small compared with the adult experience reported in a recent metanalysis including 3086 patients.²² This article concluded that, in adults with achalasia, LHM with added partial fundoplication provides superior and the longest-lasting symptom relief with low morbidity compared with other treatments. In children, there is lack of a uniform approach to achalasia, as there are no large studies evaluating the results of LHM compared with other techniques. Indeed, the largest studies by Esposito and colleagues³⁶ and Petrosyan and colleagues⁴⁵ include only 31 children. Moreover, all studies are retrospective reviews of case series (level 4 evidence²⁶), with a significant heterogeneity in the data available regarding the definition of symptoms and diagnostic criteria, pre- and post-LHM assessment techniques, use of additional treatment before LHM, operative technique, and results.

Fifty percent of the studies did not provide details with regards to the incidence, duration, and type of preoperative symptoms (Tables 1 and 2). The most common presenting symptom was dysphagia in 88% of cases. Emesis and regurgitations, though not clearly defined, were frequently reported. Information about clinical relevant GER was only available in five studies (Table 4); however, no evidence is presented as to by what means the diagnosis was established. Regarding the modality of diagnosis, barium meal and esophageal manometry remain commonly performed investigations (Table 3); 61% of children underwent endoscopy that, although useful to rule out an esophageal stricture, usually requires a general anesthesia in this age group. The pH-study is infrequently performed in children in the preoperative period, with only one author reporting its routine use in all patients.⁴⁰ It is questionable whether this test is actually necessary, because it can be misleading as the stagnant fluid in the lower esophagus is often acid and GER is virtually impossible as the LES is contracted; undoubtedly, preoperative GER was not commonly reported (Table 4).

Overall, 44% of patients underwent treatment before LHM (Table 2). Pneumatic dilatations were performed in 103 (32%) of patients; two patients (2%) had an esophageal perforation at the time of dilatation managed by VATS or antibiotics and bowel rest.^10,38 In children, there is limited experience with pneumatic dilatations and the overall success rate is variable between 60% and 80%. In their recent metanalysis in adults, Campos and colleagues²² reported a similar perforation rate of 1.6% and found that relief of symptoms seemed to be dependent on the dilator size, duration of dilation, and the number of repeated procedures with relieve or improvement of symptoms in 84.8% of patients at 1 month, 73.8% at 6 months, and 68.2% at 12 months. Other authors¹² have reported less encouraging results in children, with 75% of those older than 9 years ultimately requiring surgery. Nifedipine and botulinum toxin injection were used in 14% of children. Use of nifedipine therapy is a noninvasive treatment for achalasia but provides short-term clinical response with common side effects.⁵⁰ The use of botulinum toxin injections is equally not a valid long-term treatment in children due to lack of durable effects.¹¹ In adults, improvement of symptoms with botulinum toxin injection is reported in 78.7% of patients at 1 month, 70% at 3 months, 53.3% at 6 months, and 40.6% at 12 months, with 50% of cases requiring multiple injections.²² Furthermore, repeat botulinum toxin injections increase the risk of mucosal perforation during surgery and are associated with worse outcomes of a surgical myotomy when compared with patients who had no prior endoscopic treatment.^51–55 Overall, intraoperative complications occurred in 33 (10%) of children and conversion to open surgery was required in 2.7% of patients; a similar complication rate of 6.3% is reported in adults.²² However, in our systematic review, scanty information is available as to whether patients with intraoperative complications during LHM had received previous treatments except for three studies: Esposito and colleagues³⁶ reported that 1 of 3 patients with esophageal perforation had previous pneumatic dilatations. Corda and colleagues³⁴ reported 2 patients with postoperative dysphagia having had previous pneumatic dilatations with signs of fibrosis at surgery. Petrosyan and colleagues⁴⁵ reported that 5 of 6 patients with esophageal perforation had previous treatments (4 pneumatic dilatations and 1 pneumatic dilatations plus botulinum toxin injection).

The need for an additional concomitant anti-reflux procedure to prevent postoperative GER in children remains a major controversy. Our analysis identified that most children underwent a partial fundoplication, Dor, Toupet, or Thal, at the time of LHM. However, we could not identify a clear difference in incidence of postoperative GER between patients with and without fundoplication (7/271 versus 1/60, P = 1.0). This is different from the adults' practice, with results from a recent meta-analysis suggesting that adding a fundoplication to an LHM decreases the pathologic acid exposure and GER symptoms.²² Nonetheless, a previous meta-analysis of 21 studies in adults published in 2003 found no difference in the rate of GER symptoms and GER diagnosed with pH-studies in patients with and without a fundoplication.⁵⁶ As postoperative pH-studies are seldom performed in children, the actual incidence of GER after LHM is not known. The addition of a fundoplication during LHM might be justified by the assumption that the myotomy, especially if lengthy and extending on the gastric side, will expose the patient to a high risk of postoperative GER. Indeed, some studies have suggested that a lengthy myotomy on the gastric side for more than 2 cm predisposes patients to a high incidence of GER.^57–59 In a prospective, randomized double-blind trial in adults, Richards and colleagues⁶⁰ reported that the incidence of symptomatic GER was significantly higher in those without a fundoplication when the length of the gastric myotomy was the same in both groups at 1–2 cm. In a large institutional review of 500 LHM, Rosemurgy and colleagues⁶¹ found that postoperative symptoms after myotomy were similar with or without fundoplication with a gastric myotomy of 2–3 cm. One study conducted in 15 children who did not undergo fundoplication and the myotomy that was not carried out more than 0.5 cm distal to the gastro-esophageal junction showed a good to excellent outcome in 93% of cases.⁶² In addition, the study by Corda and colleagues³⁴ considered in this article reported a good outcome with no postoperative GER, even though the myotomy was carried out 1.5–2 cm onto the stomach. Based on the incidence of postoperative GER in our systematic review (e.g., 2.5% versus 3% incidence in LHM plus fundoplication versus LHM alone), a randomized controlled trial will need a total of 16,792 patients to detect differences between the two groups (α = 0.05, 80% power); a trial requiring such a large number of patients is undoubtedly not feasible, especially in children in whom the incidence of achalasia is very low.

The incidence of postoperative dysphagia, available in 17 studies, was 19%, with no difference between patients with and without fundoplication, suggesting that the resolution of dysphagia is independent of whether a fundoplication is performed.

We found an overall success rate of 85%, with 49 patients requiring a second procedure, mostly pneumatic dilatations, with 23 (7%) ultimately requiring a redo-LHM. These results are comparable to the adult population in whom LHM has a success rate of 90%.²² Nonetheless, it is important to highlight that the length of the postoperative follow-up in our systematic review is quite variable, with only eight studies^{31,33,34,40,43,45,47,49} reporting a median follow-up longer than 2 years. It is, therefore, likely that the failure rate might be underestimated due to the short postoperative follow-up available in the remaining 13 studies, especially in those with the largest number of patients.^{10,32,36,41,42,63} A surgical alternative to LHM that might offer better results in the long term is the POEM. POEM is becoming popular, and there is substantial evidence in the adult population that this procedure is associated with a low rate of complications and high effectiveness at midterm follow-up although its longer term efficacy in comparison with LHM needs to be clarified.¹⁶ However, the experience with POEM in children is still very limited. Caldaro and colleagues³³ compared the results of LHM and POEM between two groups of 9 children and concluded that the results are similar at midterm follow-up, with POEM requiring shorter operative time if performed by skilled endoscopic surgeons. Other authors^18,19 have confirmed the efficacy of POEM in small series of children, and, indeed, further large comparative studies might confirm that this technique might become an alternative to LHM in the pediatric population.

In conclusion, the experience of LHM in children is limited compared with adults, with no large studies that have extensively investigated the results of this technique and clarified whether an additional antireflux procedure is needed. We found no difference in the incidence of postoperative GER and dysphagia in patients with or without fundoplication and the time of LHM; therefore, the current evidence does not support the routine addition of a fundoplication during LHM. Further prospective studies are needed to evaluate the real incidence of GER after surgery in children. Despite the upcoming evidence on the efficacy of the POEM, the LHM remains at present the most commonly performed procedure for achalasia in children, with an overall success rate of 85%.

Footnotes

Disclosure Statement

No competing financial interests exist.

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