Background
Esophago-gastric junction outflow obstruction (EGJOO) is a relatively new clinical entity revealed by high-resolution manometry (HRM). According to the Chicago Classification, the disorder is due to a poorly relaxing lower esophageal sphincter (LES), with integrated relaxation pressure (IRP) >15 mmHg, and a preserved esophageal peristalsis.
1
This manometric diagnosis can have two different etiologies, i.e., idiopathic or secondary EGJOO. The latter may be caused by any mechanical obstruction of the esophagus, such as esophageal strictures, eosinophilic esophagitis, giant hiatal hernia, prior fundoplication or bariatric surgery, or malignancy.
2 Patients with no such anatomical obstructions are diagnosed with idiopathic EGJOO. The main clinical manifestations of idiopathic EGJOO are dysphagia, chest pain, and regurgitation.
3 For the time being, there are no published guidelines on the management and treatment of this recently identified motility disorder. Many authors have suggested using the same treatment for EGJOO as for achalasia, but this recommendation is based on only a few studies with small case series. Oral calcium-channel blockers are the initial treatment of choice, but achieve low rates of symptom relief of around 35%.
4
The aim of this prospective, controlled study was to examine the outcome of laparoscopic Heller-Dor (LHD) in patients with idiopathic EGJOO, as compared with that of patients with radiological grade I esophageal achalasia.
Results
During the study period, we examined 109 patients referred for dysphagia and/or food-regurgitation who had EGJOO diagnosed on HRM. Secondary EGJOO (i.e., associated with prior fundoplication, hiatal hernia, esophageal stenosis, or other causes) was identified in 63 patients, who were therefore excluded from the study.
Idiopathic EGJOO was diagnosed in 46 patients. Of the 36 previously untreated, 15 patients experienced no symptom improvement or reduction in IRP after 6 months of therapy with Ca2+ blockers. These patients were offered LHD and entered the study together with the 10 patients who had previously been treated endoscopically. The study population thus included 25 patients (M:F=15:10). Figure
1 shows the flowchart for the selection of our study population.
Our control population included 125 patients with radiological stage I achalasia. According to the Chicago Classification v3.0, 25 patients were classified as having pattern I, 74 had pattern II, and 26 had pattern III.
Table
2 shows the demographic and clinical parameters of the study population and control group. A history of endoscopic treatments (pneumatic dilations, botox injections, or both) was more common in the EGJOO group (40%) than in any of the 3 achalasia subgroups (16% of patients with pattern I, 12.2% of those with pattern II, and 7.7% of those with pattern III) (
p=0.01).
Table 2
Pre-operative demographic and clinical findings in the four groups of patients
Patients (n) | 25 | 25 | 74 | 26 | |
Age (years)* | 65 (50–74) | 44 (30–60) | 48 (33–61) | 56 (39–66) | <0.01 |
Sex (M: F) | 15:10 | 12:13 | 30:44 | 19:7 | 0.007 |
Symptom duration (months)* | 34 (21–60) | 24 (12–84) | 24 (23–36) | 30 (23–60) | 0.44 |
Symptom score (Eckardt score)* | 5 (3–6) | 8 (6–9) | 7 (6–8) | 7 (4–9) | <0.01 |
Previous endoscopic treatment^ | 10 (40%) | 4 (16%) | 9 (12.2%) | 2 (7.7%) | 0.01 |
Esophageal diameter (mm)* | 21 (20–29) | 30 (24–30) | 27 (23–30) | 25 (20–26) | 0.11 |
LES resting pressure (mmHg)* | 42 (27–50) | 43 (30–53) | 50 (41–60) | 49 (35–65) | 0.051 |
IRP (mmHg)* | 20 (19–23) | 27 (22–29) | 35 (26–46) | 26 (20–39) | <0.001 |
The EGJOO group had a lower preoperative IRP (20 mmHg, IQR: 19–23) than patients with achalasia (pattern I: 27 mmHg, IQR: 22–29; pattern II: 35mmHg, IQR: 26–46; pattern III: 26 mmHg, IQR: 20–39) (p<0.001).
The surgical procedure was completed laparoscopically in all patients. Mortality was nil. Intraoperative perforations were detected in two patients, one with EGJOO and one with pattern II achalasia. Both of these mucosal tears were repaired during the LHD procedure and were without further consequences. Gastrografin swallow X-ray performed on the first postoperative day after LHD revealed no mucosal tears in any of the patients.
The median follow-up was 24 months (IQR: 34–16). All patients had a lower SS after LHD; the median of preoperative SS was 7 (IQR: 5–8) while the postoperative was 0 (IQR: 0–1) (p<0.001). During the follow-up, the outcome was considered satisfactory in 96% of patients in the EGJOO group, and in 96% in the achalasia pattern I subgroup, 98.7% in the achalasia pattern II subgroup, and 96.2% in the achalasia pattern III subgroup (p=0.50). There were four treatment failures in all, one in each group or subgroup. All patients whose surgery failed subsequently underwent one or more endoscopic pneumatic dilation treatments, obtaining an improvement in their symptom scores.
Postoperative HRM showed a reduction in the LES resting pressure and IRP in all patients in all 4 groups/subgroups (
p<0.001). The median postoperative IRP was similar in all groups as well: 9 mmHg (IQR: 8–12) in the EGJOO group, 11 mmHg (IQR: 10–12) in the pattern I subgroup, 9 mmHg (IQR: 6–12) in the pattern II subgroup, and 12 mmHg (IQR: 7–14) in the pattern III subgroup (
p=0.51). In addition, 24-h pH monitoring showed comparable proportions of postoperative abnormal acid exposure in all groups/subgroups, affecting 14.3% of EGJOO patients, 8.3% of achalasia pattern I patients, 8.9% of achalasia pattern II patients, and 10% of achalasia pattern III patients (
p=0.49) (Table
3).
Table 3
Post-operative parameters
Symptom score (Eckardt score)* | 0 (0–1) | 0 (0–1) | 0 (0–1) | 0 (0–0) | 0.20 |
LES resting pressure (mmHg)* | 19 (15–22) | 17 (16–18) | 18 (13–23) | 17 (16–18) | 0.41 |
IRP (mmHg)* | 9 (8–12) | 11 (10–12) | 9 (6–12) | 12 (7–14) | 0.51 |
Positive outcome | 96% | 96% | 98.7% | 96.2% | 0.50 |
Abnormal 24-h pH-monitoring | 14.3% | 8.3% | 8.9% | 10% | 0.49 |
Discussion
The advent and now widespread diffusion of HRM prompted a new classification of esophageal motility disorders, the Chicago Classification, which is currently in its 3
rd version.
1 This classification is based on a dichotomous hierarchical tree where the main distinction is between a normal and an abnormal LES relaxation (IRP <15 mmHg or >15 mmHg, respectively). Combined with the absence of any peristalsis, an abnormal LES relaxation is the main characteristic of achalasia, in its 3 different manometric patterns. A poor LES relaxation associated with a preserved peristalsis (and therefore lacking one of the defining features of achalasia) can still interfere with bolus transit to the stomach and cause dysphagia. This major motility disorder is characterized by an elevated LES relaxation pressure (IRP >15 mmHg) associated with an intact peristalsis.
EGJOO is a relatively new manometric diagnostic entity, and its etiology may be idiopathic or secondary to mechanical obstructions, such as esophageal strictures, eosinophilic esophagitis, giant hiatal hernia, prior fundoplication or bariatric surgery, or malignancy.
2 Patients without any such anatomical obstruction are diagnosed with idiopathic EGJOO. The pathophysiology of “idiopathic” EGJOO is unclear, but most authors see it as a precursor or variant of achalasia, as clearly suggested by its description in the Chicago Classification as “incompletely expressed achalasia.” This theory is only supported, however, by small case series in which some EGJOO patients developed achalasia after treatment.
12
EGJOO is a relatively uncommon condition
13; as in achalasia, the main clinical manifestations of idiopathic EGJOO are dysphagia, chest pain and regurgitation,
3 and treatments that aim to relieve the idiopathic obstruction (i.e., to improve esophago-gastric junction relaxation) are the most effective. So far, the management of this novel motility disorder has been based on a handful of studies on small case series, in the light of experience gained with achalasia.
Symptoms in patients with EGJOO do not always require treatment and their final outcome varies, so deciding which patients need intervention is a key challenge in these patients’ management.
3,
13 Our study confirmed this point of view because we observed that patients who responded to medical management did not present any radiological or manometric difference compared to patients who had not a clinical improvement with Ca2+ channel blockers. Some authors suggest that 44–52% of patients diagnosed with EGJOO improve without any pharmacological or surgical therapy.
3,
14,
15 The present study enrolled only idiopathic EGJOO patients with symptoms of dysphagia and food regurgitation who did not respond to medical treatment.
Treatment options for idiopathic EGJOO described in the literature include medical, endoscopic and surgical approaches. Medical treatments such as Ca2+ channel blockers and long-acting nitrates have been used, but the few data reported by Perez-Fernandez et al. and other authors point to low clinical response rates, involving only about 50% of patients with EGJOO.
14 Porter et al. reported on the treatment of 36 EGJOO patients with botox injections. Their survival analysis showed that persistent symptom relief from a single botox injection at 2 years was just 16.8%.
16 Some authors also found that some patients treated with botox injections progressed to type 3 achalasia within 20 months of this treatment.
2
Given that idiopathic EGJOO appears to be achalasia’s precursor, Clayton et al. treated patients with pneumatic dilations. They found this a safe and effective initial treatment for idiopathic EGJOO in patients with dysphagia and abnormal esophageal emptying. The outcome was positive in 67% of patients (22/33) treated with a single dilation using a 30-mm balloon, and in 79% of patients retreated with a 35-mm balloon, after a median follow-up of around 2 years.
4
In an international multicenter study, Khashab et al. assessed the clinical outcomes of peroral endoscopic myotomy (POEM) in patients with disorders other than achalasia, i.e., EGJOO, diffuse esophageal spasm, and jackhammer esophagus. They reported a positive outcome in 93% of EGJOO patients after POEM. The main limitation of this study is the short follow-up, which was only about 6 months.
17 These positive findings were replicated by Okeke et al., however, who treated three patients with POEM, obtaining a 100% success rate after long-term follow-up.
18
The aim of the present study was to ascertain whether LHD has a role in the treatment of patients with idiopathic EGJOO, a hypothesis that—in our opinion—is confirmed by our data. For now, there are no published studies dedicated to examining the role of LHD for this recently identified clinical entity. In a recent review, Clayton et al. sought to collect all the cohorts of EGJOO patients treated with Heller myotomy: they found only two case series concerning a total of four patients treated, and all four of them experienced lasting symptom relief.
3,
4,
19 Lin et al. published a case report on a robot-assisted extended esophageal myotomy and Belsey-Mark IV fundoplication performed in a patient diagnosed with EGJOO who had suffered from severe headache using calcium channel blockers and nitrites for pain control. At one-year follow-up, the patient’s chest pain and dysphagia had improved.
20
Our study confirmed the value of surgical myotomy for EGJOO, showing that patients who underwent LHD achieved symptom relief in 96% of cases. This figure is comparable with the results achieved at our center using the same procedure in patients with esophageal achalasia.
21‐
23 Judging from our results, moreover, LHD in EGJOO was also comparable with LHD for esophageal achalasia in terms of its influence on any onset of postoperative gastroesophageal reflux.
This is the first comparative study based on prospective data collection to assess the outcome of LHD in patients with EGJOO. It has some intrinsic limitations, however, that need to be mentioned. The main limitation concerns the number of patients considered was small (though ours is the second-largest cohort of patients treated for EGJOO). A second limitation may be the exclusion of EGJOO who were referred for chest pain only (without dysphagia or food regurgitation).
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