Effects of pneumatic dilation and myotomy on esophageal function and morphology in patients with achalasia

Only two treatment modalities-pneumatic dilation and Heller myotomy-promise long-term relief from dysphagia and regurgitation in patients with achalasia. The objective of this study was to determine whether both options differ in their effects on esophageal function, morphology, and improvement in symptoms. Eighty-nine patients diagnosed with achalasia between January 1980 and December 2002 at a single center were enrolled in this study. Sixty-four patients underwent pneumatic dilation and 25 Heller myotomy in combination with an anterior semifundoplication (Dor procedure). Clinical evaluation (Eckardt-Score), esophageal manometry, and barium swallow were performed before and within 6 months after treatment. Our data shows that Heller myotomy reduces the LES resting pressure more markedly (7.9 [3.7-16.9] mm Hg) than pneumatic dilation (14.5 [2.7-36.0] mm Hg) (P < 0.0001) with similar pressures at diagnosis in both groups. Morphologic changes, assessed by the diameter of the esophageal corpus, were also more pronounced after surgical therapy (P > 0.05). Both options will lead to an immediate and significant improvement in symptoms, although the two treatment modalities did not differ in their subjective results. As only objective findings, such as those obtained by manometry and the timed barium swallow, have proven relevance for the assessment of long-term results, surgical therapy is the superior and more effective treatment option in patients with achalasia.     

Minimally invasive surgery for esophageal achalasia

BACKGROUND: Esophageal achalasia is characterized by loss of peristaltic activity and failure of relaxation of the lower esophageal sphincter (LES). The characteristic dysphagia may be alleviated by surgery, dilations, or botulinum toxin injections. Video-endoscopic surgery is used increasingly. PATIENTS AND METHODS: This paper reports our experience with 142 consecutive achalasia patients treated by laparoscopic Heller myotomy and Dor antireflux fundoplication and followed for a median 26 months. RESULTS: Overall, the actuarial lifetable analysis showed a 90% probability of a patient's being symptom free over a 5-year period. Radiologic assessment showed a significant reduction in esophageal diameter and manometry a significant reduction in the resting tone and residual pressure of the LES. Twenty-four-hour pH monitoring showed postoperative reflux in 6.7% of patients. Persistent dysphagia or chest pain (i.e., failure of treatment) were reported by 15 patients (10.6%): 14 of them were subsequently treated with multiple pneumatic dilations, which were successful in 12 cases. CONCLUSION: Laparoscopic Heller myotomy with Dor fundoplication is a feasible and effective treatment for achalasia, with an actuarial success rate of 90% at 5 years. With additional dilation, a 98% success rate can be achieved.     

Laparoscopic approach to esophageal perforation secondary to pneumatic dilation for achalasia

Background  Perforation of the esophagus after pneumatic dilation for achalasia is a severe complication which should be treated accurately in order to obtain a successful immediate outcome and a satisfactory result for the underlying condition. Methods  Five consecutive patients presenting with distal esophageal perforation after pneumatic dilation for achalasia were included in this study. All patients had gastrografin swallow performed to confirm the perforation, and one patient was also submitted to flexible esophagoscopy. Laparoscopic approach was performed in all patients with five portals. The phrenoesophageal membrane was opened on its anterior aspect. The distal esophagus was dissected free, and perforations were identified with the help of methylene blue or milk administration through the esophageal tube. All perforations were sutured with interrupted absorbable sutures. Contralateral myotomy and partial anterior Dor fundoplication completed the operation. Endoscopic control of length of myotomy and watertightness of mucosal closure was performed in all cases. Results  There were no intraoperative complications. After surgery all patients were maintained with nil per os until a barium swallow showed no leakage. One patient had a radiologic leakage sustained for 1 week. All patients were dismissed uneventfully. At 6 months after surgery, esophageal manometry was performed. Mean lower esophageal sphincter resting pressure had fallen from 30 to 8.7 mmHg. Conclusions  Laparoscopy offers an excellent approach to treat distal esophageal instrumental perforations, perhaps even better than open surgery. Suture of the perforation, contralateral myotomy and partial anterior fundoplication is a good option in the treatment of perforated achalasia after pneumatic dilation. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Clinical management of esophageal achalasia

In this report, we describe the clinical management of esophageal achalasia in Japan. Both balloon dilation and surgical myotomy or myectomy with antireflux procedures are accepted as the standard treatment for esophageal achalasia. In most patients balloon dilation is attempted first. If that is not sufficiently effective, they than undergo surgery. The most important point in treatment is not to repeat the dilation procedure more than twice, because patients who do not respond significantly to the first two dilation procedures are unlikely to improve after subsequent ones. Recently, many physicians and surgeons in Western countries have investigated the effects of botulinum toxin in patients with esophageal achalasia. If the safety of this treatment is confirmed in the near future, it will become a new treatment option for esophageal achalasia.     

Endoscopic and surgical management of achalasia

Summary  BACKGROUND: Achalasia is an uncommon motility disorder of the esophagus with an uncertain etiology that can go undiagnosed for years. Esophageal manometry and barium swallow are the gold standard for diagnosing achalasia. Endoscopy is considered scarcely sensitive and specific in the diagnosis of achalasia, but it has an important role in ruling out conditions secondary to other causes (i.e. pseudoachalasia). METHODS: Review on diagnosis and therapy of achalasia. RESULTS: Therapeutic options for achalasia aim to reduce lower esophageal sphincter pressure, improve esophageal emptying and relieve the symptoms of achalasia. There is currently much debate on the most effective treatment for long-term symptom relief. For decades, pneumatic dilation was the primary treatment option, with surgery relegated to an ancillary role when the former treatment failed. Recently, however, the development of minimally invasive surgical techniques enabling an effective Heller myotomy to be performed with an antireflux procedure, the treatment algorithm seems to have changed completely. Most gastroenterologists and surgeons prefer laparoscopic Heller myotomy with partial fundoplication as the primary treatment for achalasia. Controversy nonetheless remains as to the adequacy of the related myotomy and whether a concomitant antireflux procedure is really necessary and, if so, which procedure is most suitable. CONCLUSIONS: We present a review of the outcome of different achalasia treatment options with a special focus on endoscopic and laparoscopic procedures.      

Practical approaches to the surgical management of achalasia

Achalasia is a primary motor disorder of the esophagus characterized by an abnormal hypertensive, nonrelaxing lower esophageal sphincter (LES) and nonfunctioning, aperistaltic esophageal body resulting in significant regurgitation and dysphagia. The primary goal of treatment is palliation of symptoms. At present, all treatment techniques are directed at relieving the functional obstruction at the level of the LES by disruption or paralysis of the esophageal muscle constituting the LES. Destruction of the LES function also places the patient at risk for pathologic gastroesophageal reflux disease. Therefore, the treatment of patients with achalasia must strike a balance between the relief of dysphagia and potential creation of pathologic gastroesophageal reflux. The advent of laparoscopic esophageal myotomy for the treatment of achalasia over the past decade has resulted in most patients with the disease being referred to surgeons for definitive treatment. At the time of consultation the patient may present with a myriad of symptoms, investigative results, and previous treatments. Based on our experience of over 300 patients treated with surgery at our institution between 1990 and 2007, this review will address the practical problems encountered in the surgical management of achalasia.     

The scintigraphic assessment of the patients suffering from cardia achalasia,treated by pneumatic dilatation

The esophageal scintigraphy is a technique used to evaluate the motility and the clearance of the esophagus. The patients with achalasia of the cardia were evaluated, before treating them with pneumatic dilatation and after. The reason is to evaluate the efficiency of the pneumatic dilatation technique in the treatment of esophageal achalasia. The pneumatic dilatation with an instrument type Rigiflex is a well/handled and used technique in our clinic. In the study 22 patients were included and we had in view the esophageal transit time and the residuary radioactivity before and after the pneumatic dilatation. We established an important statistical improvement of the data obtained after the dilatation comparative with the data before the treatment (p < 0.01).     

Laparoscopic Heller myotomy for achalasia

BACKGROUND: Achalasia is an uncommon illness affecting 1 per 100,000 patients yearly. There is evidence to suggest viral, autoimmune, and hereditary etiologies. There are many treatment options available including medications, botulinum toxin injection, pneumatic dilation, and surgical myotomy. METHODS: We present a retrospective review of patients undergoing laparoscopic-modified Heller myotomy at a large referral and surgical training center. RESULTS: There were 36 patients identified. Thirty patients had undergone prior treatment with botulinum toxin injection, pneumatic dilation, previous Heller myotomy, or esophageal stenting. Immediate complications included mucosal perforation (2), spleen injury (1), and trocar-site infection (1). There were no postoperative esophageal leaks. Three patients suffered reflux requiring the daily use of a proton pump inhibitor 9 months after surgery. Three patients suffered recurrent dysphagia. CONCLUSIONS: Presently, there are little data to suggest an ideal management strategy in patients with achalasia. Our patient population consists predominantly of failures of other treatment methods submitted for laparoscopic myotomy. Our data suggest that laparoscopic Heller myotomy can be safely undertaken in this population, without a higher than expected rate of recurrent symptoms or reflux.     

Long-term results for Heller-myotomy with anterior semifundoplication in achalasia

INTRODUCTION: The positive success rate of cardiomyotomy in the treatment of achalasia has recently - especially in young patients - resulted in a primary operative treatment concept. Few studies of long-term effects of myotomy concerning the removal of dysphagia and the development of gastroesophageal reflux have been submitted. PATIENTS AND METHODS: In the period between September 1985 and March 2003, an open, transabdominal Heller-myotomy combined with a Dor-semifundoplication was carried out in 93 patients with achalasia. 77 patients were followed for more than 6 months postoperatively (median follow-up: 70 months). The procedure was prospectively observed, and patients were questioned concerning their clinical symptoms by means of structured interviews. X-ray examinations of the esophagus were pre- and postoperatively available of 47 patients, manometrical findings before and after myotomy of 26 patients. RESULTS: The pre-operatively existing symptoms dysphagia, regurgitation, retrosternal pain and weight-loss could be improved by myotomy in 97 % of the patients with good to excellent long-term results. Post-operatively, a significant reduction of the median maximum diameter of the esophagus of 50 mm to 30 mm was evident (p < 0.001), whereas the diameter of the cardia increased from 3 mm to 10 mm (p < 0.001). The pre-operative resting pressure of the lower esophageal sphincter (LES) of 29.3 mmHg was reduced to 7.9 mmHg (p < 0.001). Patients suffering from reflux esophagitis showed a significant lower resting pressure of the LES (4 mmHg) in comparison with patients without reflux esophagitis (8.5 mmHg) after myotomy (p=0.045). The clinical long-term results of patients with preceding pneumatic dilation did not differ significantly from those with primary myotomy. CONCLUSION: Conventional Heller-myotomy with anterior semifundoplication can in the long run remove the symptoms existent in achalasia with high efficiency. If the decrease of the post-operative resting pressure of the LES is too intense (< 5 mmHg), a possible gastroesophageal reflux has to be taken into account. The results of open cardiomyotomy have to be regarded as standard for assessing the minimal-invasive procedure.     

Long esophageal myotomy with a fundic patch procedure for treating diffuse esophageal spasm: Report of a case

A diagnosis of diffuse esophageal spasm (DES) based on radiological and manometric studies was made in a 70-year-old man who presented with severe dysphagia, vomiting, and spontaneous chest pain. The manometric studies revealed a simultaneous onset of high amplitude contractions and a hypertensive lower esophageal sphincter (LES) that was well relaxed in response to deglutition, in contrast to the incomplete relaxation seen in achalasia. Because his dysphagia was so severe and did not respond to pneumatic dilatation, the patient was treated by a long esophageal myotomy with a full thickness incision through the LES and mucosa, adding a Thal-Hatafuku procedure. The patient made a good postoperative recovery and has since been eating normally without any further dysphagia or chest pain. Good manometric and radiological results have been obtained in this patient during 5 years of follow-up.     

Management of esophageal perforation after pneumatic dilation for achalasia

Current management of esophageal perforation after pneumatic dilation for achalasia is thoracotomy and repair with myotomy. This study aims to assess the outcome of patients managed by laparotomy, and the role of laparoscopic repair. The study was carried out by means of retrospective case review and prospective follow-up with a symptom questionnaire. Results were compared with results in patients undergoing elective Heller myotomy. Over a 20-year period, 445 dilations for achalasia were performed in 371 patients. There were 10 esophageal perforations. Nine patients were referred for surgery and were successfully managed with a transabdominal repair. Laparoscopic repair was attempted in four patients but was successful in only one because of the perforation site. After a mean follow-up of 5.4 years, grade 1 or 2 Visick scores were recorded in all patients. Residual symptoms of dysphagia occurred in 67 % in the emergency group and 88% in the elective group. There was an increased incidence of heartburn compared to elective myotomy. Early operation after perforation provides good results for treatment of achalasia. Mild dysphagia persists and there is an increasing sensation of heartburn. The site of perforation is typically posterolateral, which makes laparoscopic repair difficult.     

Laparoscopic Heller myotomy relieves dysphagia in patients with achalasia and low LES pressure following pneumatic dilatation

Background: Although pneumatic dilatation is said to relieve dysphagia in achalasia if it decreases lower esophageal sphincter (LES) pressure to <10 mmHg, dysphagia persists in some cases. Performing a Heller myotomy in this setting has been challenged on the assumption that everything possible has already been done to eliminate the barrier posed by the malfunctioning sphincter. Therefore, we set out to assess the results of laparoscopic Heller myotomy and Dor fundoplication in achalasia in relation to LES pressure. Methods: Fifty-seven patients with achalasia were divided into the following three groups, based on the LES pressure and previous treatment: group A, previous balloon dilatation and LES pressure ?10 mmHg (n = 9); group B, previous balloon dilatation and LES pressure >10 mmHg (n = 23); group C, no previous balloon dilatation and LES pressure >10 mmHg (n = 25). All patients underwent a laparoscopic Heller myotomy and Dor fundoplication. The severity of dysphagia was gauged on a scale of 0-4. Results: In group A, LES pressure was 7 ± 2 mmHg preoperatively and 8 ± 3 mmHg postoperatively; the dysphagia score was 3.3 ± 0.7 preoperatively and 0.9 ± 1.1 postoperatively. Eighty-nine percent of patients had excellent or good results. In group B, LES pressure was 23 ± 8 mmHg preoperatively and 10 ± 1 mmHg postoperatively; the dysphagia score was 3.3 ± 0.7 preoperatively and 0.3 ± 0.5 postoperatively. All patients had excellent or good results. In group C, LES pressure was 23 ± 11 mmHg preoperatively and 14 ± 12 mmHg postoperatively; the dysphagia score was 3.6 ± 0.6 preoperatively and 0.2 ± 0.5 postoperatively. All patients had excellent or good results. Conclusions: These results show that (a) a LES pressure of <10 mmHg after pneumatic dilatation does not guarantee relief of dysphagia, and (b) laparoscopic Heller myotomy relieves dysphagia in most patients with a postdilatation LES pressure <10 mmHg. Thus, a laparoscopic Heller myotomy is indicated if dilatation does not relieve dysphagia, even if LES pressure has been decreased to <10 mmHg. Esophagectomy should be reserved for the occasional failure of this simpler operation. apd: 11 May 2001     

Etiology, Diagnosis, and Treatment of Failures After Laparoscopic Heller Myotomy for Achalasia

OBJECTIVE: To assess the causes of failure of laparoscopic Heller myotomy and to verify whether endoscopic pneumatic dilation is a feasible treatment. SUMMARY BACKGROUND DATA: Laparoscopic Heller myotomy has proved an effective treatment for esophageal achalasia, with good or excellent results in 90% of patients. The treatment of failures remains controversial, however. METHODS: From 1992 to 1999, 113 patients underwent laparoscopic Heller myotomy for esophageal achalasia. Ten patients (8.7%) reported dysphagia (n = 7) or chest pain (n = 3) a median of 5 months after surgery (range 1-12) and were considered surgical failures. Pre- and postoperative radiologic, manometric, and 24-hour pH monitoring findings in patients with achalasia recurrence were compared with those of 74 asymptomatic subjects. RESULTS: The preoperative characteristics of the two groups were comparable. After surgery, a decrease in resting lower esophageal sphincter pressure was observed in both groups, whereas the abdominal and overall lengths were significantly shorter among the asymptomatic patients. No patients with recurrence had abnormal gastroesophageal reflux. Based on time to recurrence and manometric and fluoroscopic findings, the etiology of the recurrences was classified as incomplete myotomy upward (n = 1), incomplete myotomy or sclerosis of the myotomy downward (n = 7), or sigmoid megaesophagus (n = 1); in one patient the authors could not establish the etiology. Seven of nine patients were effectively treated with endoscopic pneumatic dilations (median 2 dilations, range 1-4); one refused to undergo further treatment. Two patients underwent redo surgery. CONCLUSIONS: Recurrence of symptoms after myotomy is mainly related to incomplete myotomy or sclerosis of the distal site of the myotomy; it can be treated by dilations after surgery.     

Surgical treatment of achalasia: results with esophagomyotomy and Belsey repair

To address the controversy regarding the choice of operation for achalasia, the cases of 57 patients having operation, 38 for the first time (Group 1) and 19 with a previous procedure (Group 2), were reviewed. Surgical emphasis was on hiatal dissection to maximize exposure and use of the Belsey fundoplication to achieve cardiac competence without obstruction. Operative mortality was 1 (1.8%) of 57 patients. In group 1, 21 of the 38 had prior pneumatic dilations. All were treated with esophagomyotomy and a Belsey fundoplication. Clinical results are excellent or good in 30 (88%) of the 34 patients for whom follow-up is available, and are similar in patients with and without prior dilation. Lower esophageal sphincter (LES) pressure decreased from 22.3 to 7.7 mm Hg (p less than 0.001), and pH testing shows no reflux in any of 13 patients. In Group 2, previous operations were esophagomyotomy in 13, esophagomyotomy plus a Nissen fundoplication in 3, and a Nissen fundoplication only in 3. The initial operation failed because of inadequate myotomy in 6 patients, an obstructive Nissen fundoplication in 6, and reflux esophagitis in 7. In these 7 patients, acid reflux testing documented reflux due to cardiac incompetence and delayed clearance. Reoperations included takedown of a Nissen fundoplication in 6, esophagomyotomy and Belsey procedure in 15, Belsey procedure in 1, and resection plus colon interposition in 2. Clinical results are excellent or good in 12 (75%) of the patients with follow-up. These conclusions can be drawn. (1) Esophagomyotomy and Belsey fundoplication lowers LES pressure and provides good results with low risk, even after pneumatic dilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preoperative lower esophageal sphincter pressure has little influence on the outcome of laparoscopic Heller myotomy for achalasia

BACKGROUND: It is believed that in untreated patients with achalasia, the lower esophageal sphincter (LES) is almost always hypertensive and a Heller myotomy resolves symptoms by decreasing the LES pressure. The incidence of a normal or hypotensive LES in untreated achalasia patients is unknown. The goals of this study were to determine the incidence of a normal or hypotensive LES in untreated achalasia patients and the outcome of laparoscopic Heller myotomy in achalasia patients with either normal or low LES pressure. METHODS: Between January 1990 and May 2002, a diagnosis of achalasia was made in 239 patients. Among 109 patients (46%) who had not previously received any form of treatment, 53 patients underwent laparoscopic Heller myotomy and Dor fundoplication. Based on the preoperative LES pressure (normal, 14-24 mmHg) they were divided into three groups: group A--four patients (7.5%), LES pressure <14 mmHg; group B--18 patients (34%), LES pressure 14-24 mmHg; and group C-31 patients (58.5%), LES pressure >24 mmHg. RESULTS: Among the 109 untreated patients, the LES was hypertensive in 49 patients (45%), normal in 29 patients (27%), and hypotensive in 31 patients (28%). The clinical outcome was good among the three groups of patients who underwent laparoscopic Heller myotomy, with poor outcome in only approximately 10% in each group. CONCLUSIONS: These data show that in 55% of untreated. achalasia patients the LES pressure is either normal or low, and that laparoscopic Heller myotomy usually relieves symptoms regardless of preoperative LES pressure.     

Diagnosis using esophageal manometry and various loading tests

Two approaches of infusion and microtransducer manipulation are available for esophageal manometry. If esophageal peristalsis and relaxation of the lower esophageal sphincter (LES) are diminished, the diagnosis of achalasia can be made. As compared with the infusion method, the microtransducer method requires no perfusion of water and has no limit on posture, allowing successful measurement in an empty esophagus. Thus this method, which allows measurement after feeding and continuous monitoring for 24 hours, seems to be more physiological than the infusion method. With this method, however, peristasis-like contractile waves and relaxation of the LES may be observed in addition to simultaneous contractile waves, even in cases of achalasia. Although methods to observe excessive reactions of the LES often involve a loading test with gastrin or mecolyl in some institutions, a loading test with cerulein is routinely used in our department. In healthy controls, administration of cerulein usually leads to decreased LES pressure, while increased LES pressure is observed in patients with achalasia (paradoxical response).     

Diaphragmatic electromyography (DEMG) in achalasia patients

LES pressure increase following diaphragmatic contraction as a pinch-cock action acts as one of the barrier mechanism for gastroesophageal reflux. In achalasia patients, incomplete LES relaxation following wet swallow is one of the characteristic manometric findings, along with loss of peristalsis. On the other hand, it has been reported that swallowing effort or esophageal distention have no effect on the increase of LES pressure induced by diaphragmatic contraction, which condition is similar to achalasia. Therefore, to evaluate that whether diaphragmatic contraction is involved in the cause of achalasia, we recorded diaphragmatic electromyography (DEMG) using bipolar electrodes in 12 achalasia patients and 4 normal subjects. The phasic DEMG amplitude was 80-90 microV in normal subjects and achalasia patients. LES pressure and DEMG amplitude increased during both straight leg raising (SLR) and abdominal distention (AD), both of the maneuver induce diaphragmatic contraction, in normal subjects and achalasia patients similarly. From the data obtained with this equipment, we conclude that diaphragmatic involvement is not likely as a pathogenesis of LES dysfunction in achalasia patients.     

Robotic-assisted Heller myotomy for esophageal achalasia: feasibility, technique, and short-term outcomes

Laparoscopic Heller myotomy is the standard surgical treatment for esophageal achalasia. The incidence of esophageal perforation is about 5–10%. Robotic-assisted Heller myotomy (RAHM) offers results at least as good as those from laparoscopic procedures, additionally yielding fewer intraoperative complications. The aim of this study was to demonstrate the safety and feasibility of RAHM and its value in the treatment of esophageal achalasia. We analyzed demographics, preoperative symptoms, esophagograms, esophageal manometry, intraoperative and postoperative data of all the patients who underwent RAHM for achalasia at three institutions: 36 women and 37 men, mean age 45 ± 16 (13–87) years. Dysphagia was present in 100% of patients. Thirty-three patients (45%) had had previous endoscopic treatment: 23 patients had pneumatic dilation, four patients had Botox injections, and six patients had both. Surgical time averaged 119 min (range of 62–211); blood loss averaged 23 ml; no mucosal perforations were observed; length of hospitalization was 1.5 days; there were no deaths. At 12 months, 96% of patients had relief of their dysphagia. In conclusion, RAHM is safe and effective since there were no intraoperative esophageal perforations and relief of symptoms was achieved in 96% of the patients.     

Laparoscopic myotomy vs endoscopic dilation in the treatment of achalasia

BACKGROUND: The aim of this study was to compare the results obtained in 14 patients with achalasia who underwent laparoscopic Heller's myotomy and Dor's fundoplication with those of 16 patients who had endoscopic dilation. METHODS: The diagnosis of achalasia was confirmed by manometry, endoscopy, and barium swallow. Esophageal symptoms were quantified before and after treatment using a clinical scale. Six patients had had endoscopic dilation prior to surgery. RESULTS: Before treatment, the patients in the surgical group complained of more severe dysphagia (median, 5; range, 0-5 vs median 4; range, 3-5) and chest pain (median, 3; range, 0-5 vs median, 1.5; range, 0-5), but both groups were comparable with respect to regurgitation, heartburn, and manometric results. Both groups achieved significant clinical improvement. The severity score decreased from 5 (range, 0-5) to 1 (range, 0-3) (p < 0.05) for dysphagia to solids in the laparoscopic group and from 4 (range, 3-5) to 1 (range, 0-5) (p < 0.05) in the endoscopic group. Lower esophageal sphincter (LES) basal pressure decreased significantly in both groups (from 29.3 to 11.8 mmHg in the laparoscopic group and from 28.9 to 16.5 mmHg in the endoscopic group). After treatment, there were no significant clinical differences between the two groups. Two patients in the surgical group were converted to open surgery. CONCLUSION: Laparoscopic myotomy is as save and effective as endoscopic dilation in the treatment of achalasia.