Return of esophageal peristalsis in idiopathic achalasia.

A 47-year-old male was diagnosed as having idiopathic achalasia on the basis of clinical, roentgenographic, and manometric criteria. He was on no medication and had no disorders known to impair esophageal motility. He was treated by pneumatic dilation with a good clinical response. On reexamination 7 years later, several features considered to be typical of achalasia were no longer present. Changes included return of peristaltic activity throughout most of the body of the esophagus, failure of a direct-acting cholinergic agent to produce an increase in base line intraesophageal pressure, and failure of a direct-acting cholinergic agent to produce a heightened response at the lower esophageal sphincter (LES). Incomplete LES relaxation in response to swallowing persisted. This represents the first reported case of return of esophageal peristalsis in idiopathic achalasia.     

Intraoperative esophageal manometry in the surgical treatment of achalasia

Since 1985 we have done intraoperative manometry in 54 patients operated for achalasia. Manometry allows the assessment of the completeness of the division of the high pressure zone and ascertain the length of fundoplication (Nissen) as well as its pressure. In 26 patients pH and manometric controls were done postoperatively. Absence of reflux was noted in all and the pressure level after operation was 12.53 +/- 4.94 mmHg. Pressure measurements were not different from those of a group of 15 healthy subjects (15.2 +/- 2.45 mmHg). Dynamic studies of the high pressure zone revealed a post-deglutition relaxation of 72.5 +/- 16.32% over the basal tone. We believe that intraoperative manometry is essential in the surgical treatment of achalasia as it allows a precise control of myotomy as well as the fashioning of a high pressure zone to avoid reflux.     

Peroral endoscopic myotomy: Time to change our opinion regarding the treatment of achalasia?

Peroral endoscopic myotomy(POEM) is a new endoscopic treatment for achalasia. Compared to the classical surgical myotomy, POEM brings at least the advantage of minimal invasiveness. The data provided until now suggest that POEM offers excellent short-term symptom resolution, with improvement of dysphagia in more than90% of treated patients, with encouraging manometric outcomes and low incidence of postprocedural gastroesophageal reflux. The effectiveness of this novel therapy requires long-term follow-up and comparative studies with other treatment modalities for achalasia. This technique requires experts in interventional endoscopy, with a learning curve requiring more than 20 cases, including training on animal and cadaver models, and with a need for structured proctoring during the first cases. This review aims to summarize the data on the technique, outcomes, safety and learning curve of this new endoscopic treatment of achalasia.     

Endoscopic treatment of esophageal achalasia

Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry(HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type Ⅱ achalasia are better after treatment compared to younger patients, males and type Ⅲ achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies.     

Long-term outcome of esophageal myotomy for achalasia

AIM:Modified Heller‘s myotomy is still the first choice for achalasia and the assessment of surgical outcomes is usually made based on the subjective sensation of patients.This study was to objectively assess the long-term outcomes of esophageal myotomy for achalasia using esophageal manometry, 24-hour pH monitoring,esophageal scintigraphy and fiberoptic esophagoscopy.METHODS:From February 1979 to October 2000, 176 patients with achalasia underwent modified Heller‘s myotomy, including esophageal myotomy alone in 146 patients, myotomy in combination with Gallone or Dor antirefiux procedure in 22 and 8 patients, respectively. Clinical score,pressure of the lower esophageal sphincter (LES),esophageal clearance rate and gastroesophageal reflux were determined before and i to 22 years after surgery.RESULTS: After a median follow-up of 14 years, 84.5% of patients had a good or excellent relief of symptoms,and clinical scores as well as resting pressures of the esophageal body and LES were reduced compared with preoperative values (P<0.001).However,there was no significant difference in DeMeester score between pre-and postoperative patients(P=0.51).Esophageal transit was improved in postoperative patients, but still slower than that in normal controls. The incidence of gastroesophageal reflux in patients who underwent esophageal myotomy alone was 63.6% compared to 27.3% in those who underwent myotomy and antirefiux procedure (P=-0.087). Three (1.7%) patients were complicated with esophageal cancer after surgery.CONCLUSION: Esophageal myotomy for achalasia can reduce the resting pressures of the esophageal body and LES and improve esophageal transit and dysphagia. Myotomy in combination with antireflux procedure can prevent gastroesophageal reflux to a certain extent,but further randomized studies should be carried out to demonstrate its efficacy.     

Factors Involved in the Return of Peristalsis in Patients with Achalasia of the Cardia after Heller's Myotomy

Objective : To assess the reappearance of peristalsis in a group of 45 patients with achalasia of the cardia undergoing surgery and to analyze the factors involved in this phenomenon. Methods : According to the postoperative manometric data, the 45 patients were divided into two groups, depending on whether or not they presented a return of peristalsis. A statistical comparison of age, sex, duration of the disease, pre- and postoperative radiological diameter of the esophagus, classic or vigorous nature of the achalasia, and manometric data of the lower esophageal sphincter and esophageal body was made. Results : In 46.6% of the patients, peristalsis returned to the upper esophagus, and 100% of the waves were progressive; in 24.4%, peristalsis returned to the middle third also, but only 50% of the waves were progressive; and in 8.8% (four patients), peristaltic activity returned to the whole esophagus, but only 40% of the waves were progressive. The group of patients with a return of peristalsis had a shorter duration of dys-phagia, less preoperative dilation of the esophagus, and a greater contractile activity of the esophageal body. Conclusions : Return of peristalsis is a frequent phenomenon after myotomy in patients with achalasia of the cardia, especially in cases of short clinical evolution, little esophageal dilation, and a conserved contractile capacity, although its accurate production mechanism is unknown.     

Transition from diffuse esophageal spasm to achalasia.

A 19-year-old man first presented with clinical, radiological, and manometric features of diffuse spasm. Within a year his motility disorder progressed to "vigorous" and, finally, classic achalasia. After pneumatic dilatation and subsequent long myotomy, the features of classic achalasia disappeared and he again exhibited radiological and manometric evidence of "vigorous" achalasia. The evolution of this patient's disease provides evidence that diffuse spasm and achalasia are different stages of the same disease and lie at opposite ends of a spectrum of related esophageal motility disorders.     

Functional analysis of long‐term outcome after Heller's myotomy for achalasia

Treatment of achalasia aims at reducing the pressure of the lower esophageal sphincter (LES) and palliate symptoms. Our objective in this study was to investigate functional changes of the esophagus after Heller myotomy and evaluate their influence on postoperative gastroesophageal reflux and esophageal morphologic changes. Between 1980 and 2003, 216 patients with achalasia underwent Heller myotomy, associated with anterior partial fundoplication (Dor fundoplication). Preoperative and long‐term outcome data were collected from these patients at our hospital. The objective was to analyze esophageal functional results after Heller myotomy in the long term. Results were classified as excellent, good, fair, or poor, according to Vantrappen and Hellemans’ modified classification. One‐year, 2‐year, 5‐year, 10‐year, and 20‐year postoperative follow‐up information was available in 100% of all patients, 91.7%, 85.1%, 60%, 52.6%, and 45.9%, respectively. There were no perioperative deaths. One year after the surgery, all patients had a significant reduction in symptoms of dysphagia and regurgitation. Five years, 10 years, 15 years, and 20 years after surgery, there were 77.2% of patients (142 in 184), 68.1%, 57.1%, and 54.5%, respectively, who were satisfied (excellent to good) with surgery. No esophageal peristalsis was demonstrated in patients during follow‐up. Contractile waves in the body of the esophagus were simultaneous. The difference in the distal esophageal amplitude, the LES relaxation rate, and LES pressures in the anterior wall and/ or two sides was significant (P < 0.05) when compared before and after operation. However, there was no significant difference in the LES length and LES pressure in the posterior side. The change of direction of the LES pressure and the relaxation of LES correlate with long‐term outcomes. Postoperative gastroesophageal reflux rates, including nocturnal reflux, increased with time. The percentage of patients whose esophageal diameter became normal or remained mildly increased with time in the first 10 years after surgery changed significantly. Myotomy is an effective way to palliate symptoms in patients with achalasia. Adequate myotomy can lead to reduction of LES pressure in two or three directions, which may facilitate esophageal emptying by gravity. Surgical intervention does not lead to the return of esophageal peristalsis. Functional damage of LES in patients with achalasia is irreversible.     

Use of botulinum toxin as a diagnostic/therapeutic trial to help clarify an indication for definitive therapy in patients with achalasia

OBJECTIVE: Intrasphincteric injection of botulinum toxin is useful in achalasia but is limited by its short term efficacy. The aim of this study was to evaluate the use of botulinum toxin in selected patients in whom its short duration of action may be useful in guiding therapy before considering more invasive procedures that might not be indicated. METHODS: Over a 3 yr period, botulinum toxin was injected into the lower esophageal sphincter in patients with: 1) symptoms consistent with achalasia but insufficient manometric criteria to make the diagnosis; 2) complex clinical situations in which there were factors in addition to achalasia that may be contributing to the patient's symptoms and that required different treatment; 3) atypical manifestations of achalasia; 4) advanced achalasia in which it was unclear that sphincter-directed therapy (vs esophagectomy) would be of benefit; and 5) after Heller myotomy. Clinical response was assessed mostly by symptom improvement, but in some patients follow-up barium swallow or radioscintigraphy was available. RESULTS: Eleven patients were identified. Ten had complete symptomatic response to the injection. Two patients have undergone subsequent successful pneumatic dilation, one a successful laparoscopic myotomy, and another currently scheduled for surgical myotomy. The only patient without response had advanced achalasia requiring esophagectomy. CONCLUSIONS: Intrasphincteric injection of botulinum toxin into the lower esophageal sphincter is a useful and safe means of guiding therapy in those patients with a variant of achalasia, atypical achalasia, or complex achalasia in which it is unclear that more invasive procedures such as pneumatic dilation or surgical myotomy are the correct therapy.     

Objective assessment of gastroesophageal reflux after extended Heller myotomy and total fundoplication for achalasia with the use of 24‐hour combined multichannel intraluminal impedance and pH monitoring (MII‐pH)

SUMMARY. This study aims to evaluate by the use of 24‐hour combined multichannel intraluminal impedance and pH monitoring (MII‐pH) the efficacy of the Nissen fundoplication in controlling both acid and nonacid gastroesophageal reflux (GER) in patients that underwent Heller myotomy for achalasia. It has been demonstrated that fundoplication prevents the pathologic acid GER after Heller myotomy, but no objective data exists on the efficacy of this antireflux surgery in controlling all types of reflux events. The study population consisted of 20 patients that underwent laparoscopic Heller myotomy and Nissen fundoplication for achalasia. All patients were investigated with manometry and MII‐pH. MII‐pH showed no evidence of postoperative pathologic GER. The overall number of GER episodes was normal in both the upright and recumbent position. This reduction was obtained because of the postoperative control of both the acid and nonacid reflux episodes. The Nissen fundoplication adequately controls both acid and nonacid GER after extended Heller myotomy. Further controls with MII‐pH are warranted to check at a longer follow‐up for the efficacy of this antireflux procedure in achalasic patients.     

Oesophageal motility disorders

Oesophageal motility disorders comprise various abnormal manometric patterns which usually present with dysphagia or chest pain. Some, such as achalasia, are diseases with a well defined pathology, characteristic manometric features, and good response to treatments directed at the pathophysiological abnormalities. Other disorders, such as diffuse oesophageal spasm and hypercontracting oesophagus, have no well defined pathology and could represent a range of motility changes associated with subtle neuropathic changes, gastro-oesophageal reflux, and anxiety states. Although manometric patterns have been defined for these disorders, the relation with symptoms is poorly defined and the response to medical or surgical therapy unpredictable. Hypocontracting oesophagus is generally caused by weak musculature commonly associated with gastro-oesophageal reflux disease. Secondary oesophageal motility disorders can be caused by collagen vascular diseases, diabetes, Chagas' disease, amyloidosis, alcoholism, myxo-oedema, multiple sclerosis, idiopathic pseudo-obstruction, or the ageing process.     

The comparisons of different therapeutic modalities for idiopathic achalasia: A systematic review and network meta-analysis

Background: Current guidelines recommend per-oral endoscopic myotomy (POEM) and laparoscopic Heller''s myotomy (LHM) as first-line treatment of idiopathic achalasia, but the optimum choice between different endoscopic and surgical modalities remains inconclusive. We conducted a network meta-analysis to compare the efficacy of 8 treatments for idiopathic achalasia.Materials and methods: Three major bibliographic databases were reviewed for enrollment of randomized controlled trials between January 2000 and June 2021. We included adults with idiopathic achalasia and compared two or more of eight interventions including botulinum toxin injection (BTI), pneumatic dilation (PD), BTI + PD, LHM without fundoplication, LHM followed with Dor or Toupet fundoplication, and POEM using either the anterior or posterior approach. Our focus was on clinical success rate, postsurgical acid reflux, and moderate-to-severe adverse events.Results: Twenty-four studies involved a total of 1987 participants for analysis. When compared with PD, POEM with anterior approach, POEM with posterior approach, LHM + Toupet, and LHM + Dor were all significantly superior to the other regimens in short-term efficacy, with POEM with anterior approach and LHM + Dor showing better improvement in mid-term efficacy. BTI showed a significantly lower efficacy than PD in both periods. Regarding safety, only LHM without fundoplication was significantly associated with higher acid reflux than PD, while LHM + Toupet, LHM without fundoplication, and LHM + Dor showed a non-significant increase in moderate-to-severe adverse events.Conclusions: For idiopathic achalasia, we suggest that POEM with an anterior or posterior approach and LHM with Dor or Toupet fundoplication be initially recommended. On the contrary, both LHM without fundoplication and BTI are not recommended as definitive therapy.     

Achalasia： A review of Western and Iranian experiences

Achalasia is a primary motor disorder of the esophagus, in which esophageal emptying is impaired.Diagnosis of achalasia is based on clinical findings. The diagnosis is confirmed by radiographic, endoscopic,and manometric evaluations. Several treatments for achalasia have been introduced. We searched the PubMed Database for original articles and metaanalyses about achalasia to summarize the current knowledge regarding this disease, with particular focus on different procedures that are used for treatment of achalasia. We also report the Iranian experience of treatment of this disease, since it could be considered as a model for mediumresource countries. Myotomy,particularly laparoscopic myotomy with fundoplication,is the most effective treatment for achalasia.Compared to other treatments, however, the initial cost of myotomy is usually higher and the recovery period is longer. When performing myotomy is not indicated or not possible, graded pneumatic dilation with slow rate of balloon inflation seems to be an effective and safe initial alternative. Injection of botulinum toxin into the lower esophageal sphincter before pneumatic dilation may increase remission rates. However, this needs to be confirmed in further studies. Due to lack of adequate information regarding the role of expandable stents in the treatment of achalasia, insertion of stents does not currently seem to be a recommended treatment. In summary, laparoscopic myotomy can be considered as the procedure of choice for treatment of achalasia. Graded pneumatic dilation is an effective alternative when the performance of myotomy is not possible for any reason.     

Achalasia: A review of Western and Iranian experiences

Achalasia is a primary motor disorder of the esophagus, in which esophageal emptying is impaired.Diagnosis of achalasia is based on clinical findings. The diagnosis is confirmed by radiographic, endoscopic,and manometric evaluations. Several treatments for achalasia have been introduced. We searched the PubMed Database for original articles and metaanalyses about achalasia to summarize the current knowledge regarding this disease, with particular focus on different procedures that are used for treatment of achalasia. We also report the Iranian experience of treatment of this disease, since it could be considered as a model for mediumresource countries. Myotomy,particularly laparoscopic myotomy with fundoplication,is the most effective treatment for achalasia.Compared to other treatments, however, the initial cost of myotomy is usually higher and the recovery period is longer. When performing myotomy is not indicated or not possible, graded pneumatic dilation with slow rate of balloon inflation seems to be an effective and safe initial alternative. Injection of botulinum toxin into the lower esophageal sphincter before pneumatic dilation may increase remission rates. However, this needs to be confirmed in further studies. Due to lack of adequate information regarding the role of expandable stents in the treatment of achalasia, insertion of stents does not currently seem to be a recommended treatment. In summary, laparoscopic myotomy can be considered as the procedure of choice for treatment of achalasia. Graded pneumatic dilation is an effective alternative when the performance of myotomy is not possible for any reason.     

A clinical trial with pre- and post-treatment manometry comparing pneumatic dilation with bouginage for treatment of Chagas' megaesophagus

The physiologic similarities between the megaesophagus of Chagas' disease and idiopathic achalasia are well documented. Therefore, it would seem reasonable that comparisons of controlled trials of therapy for the more common Chagas' megaesophagus could be applied to idiopathic achalasia, where the paucity of cases makes such a controlled comparison difficult. We had the opportunity to study 18 patients with achalasia secondary to Chagas' disease. All of the patients were from the mid central states of Brazil, all had symptoms of dysphagia and radiographic documentation of dilated esophagus and abnormal peristalsis (Rezende Groups II and III), as well as positive serologic evidence of Chagas' disease. Perfused intraluminal manometric studies were performed on all patients. Resting sphincter pressures ranged from 20-35 mm./Hg., mean of 25 (normal 5-12 mm./Hg.) with aperistalsis. Patients were randomly dilated with either bouginage (44-55 ff catheter) or pneumatic dilator (4-4.5 kg./6.5 cm.2 x 2 min.). Although all patients reported symptomatic improvement several days after either procedure, repeat manometric tracings demonstrated no change in the sphincter pressure in the bouginage group. The pneumatically dilated group, however, demonstrated a decrease in sphincter pressure to normal levels (mean 12 mm./Hg.). Follow-up studies one year after the procedure confirmed the persistence of normal sphincter pressure in the pneumatically dilated group but no change, as well as return of initial symptoms, in the bouginage group.     

Chest pain in achalasia: patient characteristics and clinical course.

BACKGROUND & AIMS: In this prospective study, the prevalence of episodic pain in patients with achalasia was investigated, risk factors for its occurrence were determined, and its long-term clinical course was evaluated. METHODS: Over an 18-year period, patients with newly diagnosed achalasia were followed up at 2-year intervals. At the first visit and after each treatment, all patients underwent manometric, endoscopic, and radiographic examinations. In addition, structured interviews were performed during each patient visit and at 2-year intervals. Potential risk factors for the presence or absence of chest pain were evaluated with the use of a logistic model. To determine the evolution of this symptom, Kaplan-Meier life-table analyses were performed. RESULTS: Among 101 patients with achalasia, 64 reported chest pain and 37 had never had this symptom. Neither manometric nor radiographic findings predicted the occurrence of retrosternal pain. However, patients with chest pain were significantly younger than those without, and they had a shorter duration of symptoms. Treatment with pneumatic dilatation or myotomy effectively diminished dysphagia but had little effect on the occurrence of retrosternal pain. However, over a course of several years, chest pain diminished in most patients and disappeared in a minority of them. CONCLUSIONS: Chest pain is a common symptom of achalasia and predominantly affects younger patients. Its cause remains unknown, and no treatment exists to effectively relieve this symptom. However, with advancing age, the frequency of chest pain will spontaneously diminish in most patients.     

Laparoscopic Heller myotomy with or without partial fundoplication： A matter of debate

AIM: To present our experience of laparoscopic Heller stretching myotomy followed by His angle reconstruction as surgical approach to esophageal achalasia. METHODS: Thirty-two patients underwent laparoscopic Heller myotomy; an anterior partial fundoplication in 17, and angle of His reconstruction in 15 cases represented the antireflux procedure of choice. RESULTS: There were no morbidity and mortality recorded in both anterior funduplication and angle of His reconstruction groups. No differences were detected in terms of recurrent dysphagia, p.o. reflux or medical therapy. CONCLUSION: To reduce the incidence of recurrent achalasia after laparoscopic Heller myotomy, we believe that His' angle reconstruction is a safe and effective alternative to the anterior fundoplication.     

Results of surgical treatment of achalasia of the esophagus.

Surgical treatment of patients with achalasia of the esophagus results in dramatic and permanent relief in almost 90% of the patients. The abdominal approach seems to produce more reflux than the thoracic route. There is evidence that extending myotomy more than 10 mm onto the stomach increases reflux. The length of the hypertensive gastroesophageal sphincter is almost 4 cms and an anterior esophagomyotomy of 5 to 6 cms is long enough in these patients. Extending the section 7 to 10 cms proximally would seem to be unnecessary and may provoke more reflux. The mortality rate of the surgical procedure is very low--less than 0.2%. Postoperative complications can occur in almost 4% of them, esophageal leakage being the most dangerous. The most frequent late complication is gastroesophageal reflux, which can occur symptomatically in 10% of the cases and by objective studies in almost 20% of the patients. The addition of antireflux surgery is controversial. If performed, it must be ensured that no obstruction can occur; esophageal emptying in an aperistalsic esophagus can be seriously delayed. Comparative studies suggest that the addition of antireflux surgery gives better results than myotomy alone. Surgeons performing this operative technique should be specialized digestive tract surgeons and familiar with manometric studies.     

Shorter myotomy on the gastric site (≤2.5 cm) provides adequate relief of dysphagia in achalasia patients

The right length of the myotomy on the gastric side for esophageal achalasia is still a debated issue. We aimed to investigate the final outcome after classic myotomy (CM) as compared with a longer myotomy on the gastric side (LM) in two cohorts of achalasia patients. Forty‐four achalasia patients who underwent laparoscopic Heller–Dor were considered; patients with a sigmoid‐shaped esophagus were excluded. Symptoms were scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain. Barium swallow, endoscopy, and esophageal manometry were performed before and 6 months after the surgical treatment; 24‐hour pH‐monitoring was also performed 6 months after the procedure. CM was defined as a gastric myotomy length in the range of 1.5–2.0 cm, while LM was 2.5–3 cm in length. The surgical treatment (CM or LM) was adopted in two consecutive cohorts. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. >8). Of the 44 patients representing the study population, 20 had CM and 24 had LM. The patients' demographic and clinical parameters (age, sex, symptom score, duration of symptoms, esophageal diameter, and manometric pattern) were similar in the two groups. The median follow up was 24 months (interquartile range 12–39). One patient in each group was classified as a treatment failure. After the treatment, there was a significant decrease in both groups' symptom score, and resting and residual pressure (P < 0.01), with no statistically significant differences between the two groups in terms of postoperative symptom score, resting and residual pressure, or total and abdominal lower esophageal sphincter length and esophageal diameter. Extending the length of the myotomy on the gastric side does not seem to change the final outcome of the laparoscopic Heller–Dor procedure.     

Esophageal Motility of Patients with Chagas' Disease and Idiopathic Achalasia

Chagas' disease and idiopathic achalasia have the same neuropathic lesion—the loss of ganglion cells within the esophageal myenteric plexus—with similar clinical, radiologic, and manometric features. However, it is suggested that there are some differences between them. We studied the esophageal motility of 45 patients with Chagas' disease (seven with esophageal dilation), 27 patients with idiopathic achalasia (13 with esophageal dilation), and 40 asymptomatic volunteers. We used the manometric method with continuous perfusion. The lower esophageal sphincter (LES) pressure was measured by the rapid pull-through method. Esophageal contractions was evaluated at 5, 10, and 15 cm above the LES, after 10 swallows of a 5-ml bolus of water alternated with 10 dry swallows. LES pressure was higher in achalasia than in Chagas' disease patients and controls (P < 0.05). Amplitude of contraction was lower in all patient groups compared with controls (P < 0.01) and lower in patients with dilation compared with patients without dilation (P < 0.05). The contraction duration was longer in patients with achalasia than in patients with Chagas' disease and controls (P < 0.05). The percentage of failed contractions was higher in Chagas' disease than in achalasia and controls (P < 0.05), and the percentage of simultaneous contractions was higher in patients with idiopathic achalasia than in patients with Chagas' disease and controls (P < 0.05). The results suggest the possibility that the extent of impairment of esophageal innervation differs between Chagas' disease and idiopathic achalasia.