Multiple rapid swallows (MRS) is a provocative test for assessment of contraction reserve, however reproducibility on repetitive MRS is incompletely understood. Our aim was to determine the optimal number of MRS sequences for consistent assessment of contraction reserve.

One hundred and fifty-nine consecutive patients (79 IEM and 80 normal motility) who underwent high-resolution manometers were enrolled. Ten single swallows (SS) and 10 MRS were performed. Gold standard for evaluation of the contraction reserve was the ratio between the mean DCI of 10 MRS and the mean DCI of 10 SS (MRS/SS DCI ratio). Rates of false negatives and false positives were calculated for increasing numbers of MRS sequences, using either mean DCI or the MRS with the highest DCI.

According to the gold standard, 50 IEM and 50 normal motility patients had contraction reserve. With progressively increasing numbers of MRS sequences, contraction reserve was detected using mean MRS DCI within three and four MRS sequences in IEM and normal motility respectively, whereas two and three MRS sequences were needed using the MRS sequence with the highest DCI. False positives were much higher with highest DCI method compared with mean DCI, (22% vs 9% respectively in IEM; 24% vs 9% in normal motility) when three MRS sequences were considered.

At least three MRS are needed to reliably assess contraction reserve. The mean DCI of the three MRS sequences is the best variable to utilize as evidence of contraction reserve.

Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns.

We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre-operative (conventional) manometry tracings were reviewed by two expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes.

Manometry studies were categorized as follows: type I (n = 20), type II (n = 20), type III (n = 3), and esophagogastric junction outflow obstruction (EGJOO) (n = 3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs 13/20, p = 0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank-Sum, p = 0.016). CD3(+) /CD8(+) cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO).

The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings - from complete neuronal loss to lymphocytic inflammation to apparently normal histopathology - emphasizes that 'achalasia' represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction.

High-resolution manometry and recently described analysis algorithms, summarized in the Chicago Classification, have increased the recognition of achalasia. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or with peristalsis. Any of these phenotypes could indicate achalasia; however, without a disease-specific biomarker, no manometric pattern is absolutely specific. Laboratory studies indicate that achalasia is an autoimmune disease in which esophageal myenteric neurons are attacked in a cell-mediated and antibody-mediated immune response against an uncertain antigen. This autoimmune response could be related to infection of genetically predisposed subjects with herpes simplex virus 1, although there is substantial heterogeneity among patients. At one end of the spectrum is complete aganglionosis in patients with end-stage or fulminant disease. At the opposite extreme is type III (spastic) achalasia, which has no demonstrated neuronal loss but only impaired inhibitory postganglionic neuron function; it is often associated with accentuated contractility and could be mediated by cytokine-induced alterations in gene expression. Distinct from these extremes is progressive plexopathy, which likely arises from achalasia with preserved peristalsis and then develops into type II achalasia and then type I achalasia. Variations in its extent and rate of progression are likely related to the intensity of the cytotoxic T-cell assault on the myenteric plexus. Moving forward, we need to integrate the knowledge we have gained into treatment paradigms that are specific for individual phenotypes of achalasia and away from the one-size-fits-all approach.

Radical treatment for achalasia is currently unavailable. At present, most palliative procedures are designed improve the passage of food through the gastroesophageal junction and thereby alleviate symptoms. Drug therapy is of limited, transient effectiveness. Pneumatic dilation (PD) is considered superior to endoscopic botulinum toxin injection (EBTI). The mainstay of surgical treatment for achalasia is laparoscopic Heller myotomy (LHM) with fundoplication, currently considered superior to PD. Per oral endoscopic myotomy (POEM), a "state-of-the-art" procedure for minimally invasive surgery, holds great promise for the future management of achalasia. Definitive conclusions regarding the benefits and risks of currently available treatments for achalasia must await the accumulation of evidence from well-designed clinical trials.

Previous studies have correlated esophageal body motility findings in idiopathic (IdAc) achalasia and achalasia secondary to Chagas' disease (ChAc) with degree of megaesophagus. The aim of this study was to compare esophageal body manometric data in patients with IdAc and achalasia secondary to Chagas' disease and correlate it with the degree of megaesophagus and symptom duration. One hundred nontreated patients with achalasia, 79% IdAc and 21% secondary to ChAc were compared with regards to age of presentation, duration of symptoms, amplitude and duration of simultaneous contractions, frequency of failed contractions, and degree of megaesophagus. Seventy-one percent of patients were classified as nonadvanced megaesophagus (60 [76%] with IdAc and 11 [52%] with ChAc) and 29% as advanced megaesophagus (19 [24%] with IdAc and 10 [48%] with ChAc, P= 0.04). In IdAc but not in ChAc, the symptom duration was significantly longer in advanced megaesophagus (A) compared with nonadvanced megaesophagus (NA) (34.8 ± 6.3 months vs. 95.4 ± 22.2 months, P= 0.001). There was no difference in amplitude and duration of simultaneous contractions in both achalasia groups (P > 0.05). Duration of contractions were longer in IdAc compared with ChAc in (NA) (P < 0.05), but not in (A). In IdAc but not in ChAc the amplitude of simultaneous contractions decreased with increased esophageal dilatation (P < 0.05). In ChAc but not in IdAC, the duration of contractions increased with esophageal dilatation (P < 0.05). Failed contractions were more frequent in ChAc group (28.6%) than in IdAc (10% -P= 0.03). Patients with ChAc have a higher prevalence of advanced megaesophagus compared with IdAc at diagnosis. In IdAc there was a strong correlation between advanced megaesophagus and longer symptom duration, suggesting disease progression over time, not observed in ChAc in which a more extensive denervation occurs earlier in the disease process.

High-resolution manometry (HRM) makes it possible to better evaluate spatial and temporal characteristics of esophageal motor function. This technology is revealing new observations regarding disordered motor function in esophageal diseases.

The aim of this study was to define the essential features of achalasia using HRM.

We performed HRM on 27 patients with achalasia, 10 patients with gastroesophageal reflux disease, and 10 controls. Ten 5 mL water swallows were recorded with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals.

The resting lower esophageal sphincter pressure was greater in achalasia than in controls or gastroesophageal reflux disease. There was an absence of peristalsis in the smooth muscle esophagus and failure of lower esophageal sphincter relaxation. The resting upper esophageal sphincter pressure was not different among the 3 groups. In addition to the typical manometric findings of achalasia, new observations are included. Esophageal shortening, pressurization of the esophagus, and rhythmic contractions of the upper esophageal sphincter and striated muscle esophagus were frequently observed.

HRM demonstrates alterations of esophageal motor function in achalasia that are not easily observed with other manometric techniques.

Achalasia is a primary oesophageal motility disorder resulting from damage to the ganglion cells of the myenteric plexus. Impaired relaxation of the lower oesophageal sphincter and aperistalsis causes its cardinal symptoms of dysphagia, chest pain and reflux-type symptoms. Management is somewhat controversial, with options including systemic and local pharmacotherapy, dilatation and oesophagomyotomy. We review the presentation, investigation and management of oesophageal achalasia and make an argument for primary surgical management.

We performed a Medline search of the term 'achalasia', limiting the search to clinical trials and meta-analyses. We then selected articles based on their abstracts using four main criteria: previously unreported findings, previously unreported techniques, size of patient cohort and journal impact factor. References in selected articles were manually searched for other relevant articles.

Achalasia has been managed using a variety of techniques including systemic and local pharmacotherapy, forced dilatation and oesophagomyotomy. Success rates vary widely between techniques. Mechanical disruption ofthe lower oesophageal sphincter is most successful.

In achalasia, mechanical disruption of the lower oesophageal sphincter using forced dilatation or surgical myotomy offers the only realistic prospect of long-term symptom relief. Recent evidence suggests that previous medical treatment or dilatation makes oesophagomyotomy more difficult and increases the risk of complications. As the morbidity associated with surgery continues to decrease with improvements in minimal access techniques, the argument for primary management of achalasia with oesophagomyotomy becomes more compelling.

The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia, feeding intolerance, gastroesophageal reflux, abdominal pain, and constipation are few of the medical problems frequently encountered in children with developmental disabilities. Alteration in bowel motility have been described in most of these disorders and can results from a primary defect in the enteric neurons or central modulation. The development and physiology of the enteric nervous system is discussed along with the basic mechanisms involved in controlling various functions of the gastrointestinal tract. The intestinal motility, neurogastric reflexes, and brain perception of visceral hyperalgesia are also discussed. This will help better understand the pathophysiology of these disorders in children with developmental disabilities.

Achalasia and gastroesophageal reflux disease (GERD) represent diverse physiologic disorders both of which result from lower esophageal sphincter (LES) dysfunction. Fortunately, both diseases are benign and amenable to surgically corrective therapies. Achalasia is characterized by destruction of the smooth muscle ganglion cells of the myenteric plexus (Auerbach) resulting in motor dysfunction, incomplete LES relaxation, and progressive esophageal dilation. GERD is frequently characterized by hypotonia or shortening of the LES. Local anatomical derangements such as a hiatal hernia (eg, sliding type I hernia) can predispose to GERD. Other predisposing factors for GERD include obesity, smoking, alcohol, and pregnancy. Transient LES relaxation is the most significant factor in the development of GERD. Transient LES relaxations last from 10 to 45 seconds and are not related to swallowing. The diagnostic workup of achalasia and GERD may include barium esophagram, upper gastrointestinal endoscopy, pH monitoring, and esophageal manometry. The different medical treatment options for achalasia comprise pharmacologic treatment, botulinum toxin, and balloon dilation. Surgical interventions include Heller myotomy, which is usually combined with a partial fundoplication. GERD is managed by treating the predisposing factors, using medications (ie, anatacids or proton pump inhibitors) and surgery (ie, fundoplication). Recently, endoluminal therapy has been employed in the treatment of GERD with promising short-term results.

Extra-oesophageal autonomic dysfunction in idiopathic achalasia is not well documented, due to contradictory results reported. We aimed to study the cardiovascular and pancreatic autonomic function in patients with idiopathic achalasia. Thirty patients with idiopathic achalasia (16M/14F; 34.5 +/- 10.8 years) and 30 healthy volunteers (13M/17F; 34.8 +/- 10.7 years) were prospectively studied. Age >60 years and conditions affecting results of autonomic evaluation were excluded. Both groups underwent the sham feeding test and plasmatic levels of pancreatic polypeptide (PP) were determined by radioimmunoassay (basal, at 5, 10, 20 and 30 min). Cardiovascular parasympathetic (deep breathing, standing, Valsalva) and sympathetic function (postural decrease of systolic blood pressure, Handgrip test) were assessed. Statistical comparison of basal and increase levels of PP and parasympathetic/sympathetic cardiovascular parameters was performed between groups. Basal levels of PP were similar in controls and patients and maximum increase of PP during sham feeding test. A similar rate of abnormal cardiovascular tests was found between groups (P > 0.05). E/I ratio was the mostly impaired parameter (patients: 36.7% vs controls: 20%, P = 0.15, chi-squared test). Autonomic cardiovascular tests and pancreatic response to vagal stimulus are not impaired in patients with primary achalasia of the oesophagus.

The radiological features of achalasia of the esophagus are well known and have been described. However, very little is known concerning the natural history of this disease. We aimed to determine the evolutive radiological changes of the esophagus in a group of patients with achalasia who had not previously undergone any treatment.

We undertook a prospective study of 14 patients with achalasia from a group of 205 patients. They included 9 women and 5 men who did not receive any treatment at the initial diagnosis. Two radiological parameters were evaluated: (a) the maximal internal diameter of the middle third of the thoracic esophagus in millimeters and (b) the internal diameter of the esophagogastric junction in millimeters.

At a mean follow-up of 5-years without any treatment, there was a significant increase in the diameter of the thoracic esophagus, with a rate of "dilatation" of 6.1 mm/year. In addition, there was a significant decrease of the internal diameter of the esophagogastric junction, with a rate of "stenosis" of 1 mm/year. The lower esophageal sphincter was hypertensive in all with an incomplete relaxation.

These results suggest that there is a progressive deterioration in the radiological parameters of the esophagus in patients with achalasia not treated over a 5-year period of observation.

Subjective assessment of primary achalasia is not accurate. We aimed to study the utility of surface area of barium retention in the objective assessment of these patients.

Subjective and objective esophageal functions of 99 patients with primary achalasia were evaluated initially and 43 of them were reevaluated 1 month after balloon dilation.

Before dilation: Ninety-nine patients were enrolled. Forty-one of them were male. The mean age was 37.5+/-15.3 years. The mean score, resting lower esophageal sphincter pressure, height, surface and volume of barium retention at 5 min were 8.03+/-3.1, 59.1+/-20 mmHg, 9.9+/-4.9 cm, and 23.6+/-13.9 cm and 53.2+/-47.7 cm, respectively. Surface area at 5 min had best correlation and predictive value for resting lower esophageal sphincter pressure. After dilation: Forty-three of 99 patients were reevaluated after balloon dilation. The mean age was 36.8+/-13.6 years. Seventeen of them were male. Mean score, resting lower esophageal sphincter pressure, height, surface area and volume of barium retention at 5 min dropped significantly after dilation. Surface area at 5 min had best correlation and predictive value for lower esophageal sphincter pressure.

Surface area of barium retention at 5 min is an accurate objective tool to assess patients with primary achalasia. It is cheap and easy to perform; therefore, it could be used more frequently in postdilation follow-up.

Pseudoachalasia is a difficult condition for the clinician to differentiate from idiopathic achalasia even by manometry, radiological studies or endoscopy. Its etiology is usually associated with tumors. In most cases, the diagnosis is made after surgical explorations. The proposed pathogenesis of the disease is considered as mechanical obstruction of the distal esophagus or infiltration of the malignancy that affects the inhibitory neurons of the meyenteric plexus in the majority of cases. Surgery has been reported as a cause of pseudoachalasia. We report a 70-year-old man who suffered from deglutination disorder caused by pseudo-achalasia after truncal vagotomy. The patient was symptom-free after a nine-year follow-up and complete recovery of esophageal motility status from pseudoachalasia after pneumatic dilations. We also reviewed the literature of pseudoachalasia.

Botulinum toxin has gained widespread acceptance as a treatment option for various spastic gastrointestinal disorders such as achalasia, gastroparesis, sphincter of Oddi dysfunction, chronic anal fissures, and pelvic floor dyssnergia, despite the lack of strong evidence supporting its use in many of these diseases. This review summarizes the trials investigating the use of BoNT since it was first utilized as a treatment in achalasia. BoNT has proven to be safe, but long-term efficacy in many disorders has not been observed, primarily due to is relatively short duration of action. BoNT may be most useful in confirming a diagnosis which can lead to a more definitive treatment modality. Furthermore, its safety profile allows it to be a useful alternative in patients who are at high risk for invasive procedures.

A standard procedure for the treatment of achalasia remains to be established. We assessed the usefulness of a laparoscopic Heller myotomy with a Toupet fundoplication (LHT).

LHT was performed in 30 patients (12 men, 18 women; mean age, 41.8 y) who had esophageal achalasia with severe dysphagia. Caution was exercised when the esophagus was pulled downward and straightened. Symptoms and esophageal function were evaluated before and after surgery.

The esophagus was straightened surgically in 22 (88%) of 25 patients with esophageal curvature on preoperative esophagography. The dysphagia score decreased to 1.7 +/- 1.2 (mean +/- SD) points from a preoperative value of 10. The lower esophageal sphincter pressure decreased significantly. Two patients (7%) had esophageal diverticula as postoperative sequelae. Pathologic acid reflex was noted in 3 patients (12%).

LHT is a useful procedure for straightening the esophagus, reducing lower esophageal sphincter pressure, and relieving dysphagia in patients with achalasia.

Achalasia, a poorly relaxing lower esophageal sphincter, produces a functional obstruction and the expected symptoms of dysphagia, regurgitation and eventually weight loss. The cause of achalasia remains largely unknown in Western countries, Chagas' disease being the most frequent etiology in Brazil. We report on two sets of monozygotic male twins with typical manifestations of achalasia. The majority of authors attribute a limited contribution unless achalasia is related to a multisystem disorder, like the triple-A or Allgrove's syndrome, an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. The four cases reported demonstrated the genetic influence of achalasia in patients without multisystem disorders. We believe that idiopathic achalasia is a syndrome with similar clinical, pathological, radiological and manometric evolution, but with a great variety of etiological agents, one of them being the congenital form.

Idiopathic achalasia is an inflammatory disease of unknown etiology characterized by esophageal aperistalsis and failure of LES relaxation due to loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus. Proposed causes of achalasia include gastroesophageal junction obstruction, neuronal degeneration, viral infection, genetic inheritance, and autoimmune disease. Current evidence suggests that the initial insult to the esophagus, perhaps a viral infection or some other environmental factor, results in myenteric plexus inflammation. The inflammation then leads to an autoimmune response in a susceptible population who may be genetically predisposed. Subsequently, chronic inflammation leads to destruction of the inhibitory myenteric ganglion cells resulting in the clinical syndrome of idiopathic achalasia. Further studies are needed to better understand the etiology and pathogenesis of achalasia-such an understanding will be important in developing safe, effective, and possibly curative therapy for achalasia.

Achalasia is a disorder of the oesophagus characterised by increased lower oesophageal sphincter (LOS) tone, lack of LOS relaxation with swallowing and aperistalsis of the body of the oesophagus. The aetiology and pathogenesis of idiopathic achalasia are still unclear, although a viral cause, genetic influences (associations with HLA loci) and autoimmune processes have been postulated. Degeneration and significant loss of nerve fibres, associated with an inflammatory infiltrate of the myenteric plexus in idiopathic achalasia, provide evidence of an immune mediated destruction of the myenteric plexus, possibly through apoptotic process. This concept is reinforced by the concomitant appearance of achalasia and Guillain-Barré syndrome (GBS) and/or Parkinson's disease, where inappropriate initiation of apoptosis has been proposed to underlie the neuronal attrition. In the same respect, Helicobacter pylori (H. pylori) infection has been associated with gastric autoimmunity, and patients infected with H. pylori have been shown to possess autoantibodies that cross-react with antigens expressed on the gastric mucosa. Furthermore, H. pylori is thought to be associated with the development of autoimmune sequelae observed in peripheral neuropathies and GBS, where autoantibodies to specific neural targets have been found to impair native neural function by inducing nerve tissue damage, possibly by apoptosis. Taken together, we assume that H. pylori infection might be a pathogenetic factor of achalasia through induction of autoimmunity and apoptosis. Whether eradication of H. pylori infection may indirectly offer benefit to the pathophysiology of idiopathic achalasia by ameliorating the apoptotic loss of ganglion cells and their axons in the oesophageal wall remains to be elucidated.

Achalasia has been described following fundoplication and is attributed to vagal nerve damage during surgery. Similarly, other traumatic events to the distal esophagus may be linked to the development of achalasia. Operative and nonoperative trauma as a possible factor in the development of achalasia was studied. A retrospective analysis of patients with achalasia (n = 64) at our institution was performed. Collected data included age, gender, symptoms, and history of operative and nonoperative traumatic events. Comparisons were made to a group of patients with similar symptoms but normal esophageal manometry (n = 73). Achalasia was diagnosed by manometry in 125 patients over a 6-year period. All patients with complete medical records (n = 64) were studied. A history of operative or nonoperative trauma to the upper gastrointestinal tract prior to the development of symptomatic achalasia was present in 16 of 64 (25%). Significantly fewer patients (9.5%) with symptoms of dysphagia, but normal manometry and upper endoscopy, had precedent trauma to the upper gastrointestinal tract (P < 0.05). All cases of nonoperative trauma occurred in motor vehicle accidents. Cases of operative trauma included coronary artery bypass surgery (n = 4), bariatric surgery (n = 2), fundoplication (n = 3), heart/lung transplantation (n = 1), and others (n = 5). Patients with proven achalasia and a history of trauma were more likely to have chest pain (RR, 4.5; P = 0.012) but less likely to have regurgitation (RR, 0.51; P = 0.01) or nausea/vomiting (RR, 0.0; P = 0.27) than those without a history of antecedent trauma. In this series, significantly more patients with achalasia had a history of preceding trauma than did patients with similar symptoms and normal esophageal manometry. Following trauma, patients may be at increased risk for developing achalasia, possibly from neuropathic dysfunction due to vagal nerve damage. Patients with posttraumatic achalasia may have symptoms which differ from those of other achalasia patients.

Detailed data on patterns of esophageal bolus transport in patients with achalasia are still lacking. To study these we applied the novel technique of multichannel intraluminal impedance measurements. Ten patients with achalasia were studied using a 16 channel system. Liquid and semisolid boluses of 10 mL were applied with the patients in a supine position. Patterns of bolus transport were determined and analyzed as compared to results obtained from 20 healthy subjects. The healthy subjects featured a unique typical primary peristalsis pattern independent of bolus viscosity. In contrast, achalasia patients demonstrated different impedance characteristics, including: (i) significantly lower baseline esophageal impedance during the resting state as compared with healthy volunteers (999 omega +/- 108 versus 2749 omega +/- 113); (ii) failed bolus transport through the esophagus in all cases; (iii) impedance evidence of luminal content regurgitation in 35% of the swallows (iv) impedance evidence of pathological air movement within the proximal esophagus during deglutition in 38% of the swallows, so called air trapping. Thus, impedance characteristics of achalasia have been defined and can be attributed to known symptoms of achalasia. They can be used as basic findings for further classification of pathological bolus transports in other esophageal motility disorders.

Esophageal peristalsis generally does not return to normal after surgical treatment of achalasia. Direct electrical stimulation of the vagus nerve is known to stimulate antegrade peristalsis in the normal esophagus; however, it is not known whether electrical stimulation will induce return of peristalsis once an achalasia-like disorder has been established. The objective of this study was to perform quantitive and qualitative measurements of motility during electrical stimulation of the vagal nerve in an animal model of achalasia. An already established and verified animal achalasia model using adult North American opossums (Didelphis virginiana) was used. Fifteen opossums were divided into three groups. Sham surgery was performed on three animals (group 1). In group 2 (n=6) a loose Gore-Tex band (110% of the esophageal circumference) was placed around the gastroesophageal junction to prevent relaxation of the lower esophageal sphincter during swallowing. In group 3 (n=6) a relatively tighter band (90% of the esophageal circumference) was used to further elevate the lower esophageal sphincter pressure. At 6 weeks, after manometric and radiolologic confirmation of achalasia, electrical stimulation of the esophagus was performed before and after removal of the band using a graduated square-wave electrical stimulus. Changes in esophageal neural plexi were assessed histologically. Pre- and postoperative manometric data were compared using standard statistical techniques. No difference was observed in esophageal characteristics and motility after sham surgery in group 1. Animals in group 2 demonstrated a vigorous variety of achalasia (high-amplitude, simultaneous, repetitive contractions), moderate esophageal dilatation, and degeneration of 40% to 60% of intramuscular nerve plexi. Animals in group 3 developed amotile achalasia with typical low-amplitude simultaneous (mirror image) contractions, severely dilated ("bird beak") esophagus, and degeneration of 50% to 65% of nerve plexi. Vagal stimulation in group 2 demonstrated a significant increase in the amplitude of contractions (P<0.001) and return of peristaltic activity in 49% of swallows before band removal. After band removal, all of the contractions were peristaltic. In group 3 vagal stimulation before and after removal of the band demonstrated a significant increase in amplitude of contractions (P<0.0001) but no return of propagative peristalsis before band removal, however, 44% of contractions were progressive in the smooth portion of the esophagus after removal of the band. Electrical stimulation of the vagus nerve improved the force of esophageal contractions irrespective of the severity of the disease; however, peristaltic activity completely returned to normal only in the vigorous (early) variety of achalasia. Removal of the functional esophageal outlet obstruction, as with a surgical myotomy, may be necessary to obtain significant peristalsis with vagal pacing in severe achalasia.

The most important etiologies of achalasia are idiopathic and related to Chagas' disease. The lower esophageal sphincter pressure (LESP) in idiopathic achalasia (Id Ach) is higher compared with a healthy group, but there are different reports in Chagasic achalasia (Ch Ach). We compared the LESP of patients with both forms of achalasia and a control group. The LESP of 213 achalasia patients without previous treatment and 32 healthy volunteers were assessed. In 126 patients, the etiology could be demonstrated using serologic tests (Id Ach, 94 and Ch Ach, 32). The LESP of 213 patients was 31.86+/-14.18 mmHg and in the control group was 17.92+/-7.03 mmHg (P < 0.0001). The LESP in Id Ach and Ch Ach was 33.28+/-13.63 mmHg and 23.5+/-12.09 mmHg (P < 0.0001), respectively. Only the Id Ach group achieved statistical difference in relation to the control group (P < 0.0001). In conclusion, the LESP of Id Ach patients was higher than in Ch Ach patients and the control group, but there was no LESP difference between the Ch Ach and control groups.

Achalasia, a motor disorder of the esophagus, is accompanied by autoimmune phenomena that could be playing a role in the pathogenesis of the disease. Our objective was to establish the genotypic frequency of the HLA-DR and DQ alleles in patients with achalasia and to establish their relationship with the presence of myenteric antiplexus antibodies in our geographic area. A total of 92 patients diagnosed with achalasia and two control groups with 275 healthy subjects were studied for HLA typing and 40 for autoantibodies determination. The myenteric antiplexus antibodies were positive in 50 patients (54.3%) and in 3 healthy subjects (7.5%) (P < 0.001). The patients showed a significantly higher frequency of DQA1*0103 and DQB1*0603 than was found in the controls. The heterodimer DQA1*0103-DQB1*0603 was increased in the patients [odds ratio (OR) = 2.57]. In regard to the association between the HLA DQA1 and DQB1 alleles and the antiplexus antibodies, these antibodies were found in greater prevalence in those patients with the DQA1*0103 and DQB1*0603 alleles, and the differences were statistically significant (OR = 3.17 and OR = 5.82, respectively). All of the women and 66.7% of the men with achalasia and the DQB1*0603 allele or the DQA1*0103-DQB1*0603 heterodimer were positive for antibodies.

Previous studies have often revealed an absence or reduction of ganglia in Auerbach's plexus in many patients with achalasia, which has been postulated to be related to the elevated lower esophageal sphincter pressure in these patients. We undertook a prospective study to determine whether microscopic changes were present in the myenteric plexus of patients with hypertensive lower esophageal sphincter, nutcracker esophagus, and diffuse esophageal spasm and if there was a correlation with lower esophageal sphincter pressure. Nine patients (3 men and 6 women; ages 49 to 72 years, mean 58 years) underwent a laparoscopic esophagomyotomy with fundoplication for symptomatic spastic motility disorder. A 10 mm x 5 mm segment of esophageal muscle was removed from the border of the myotomy incision, fixed in formalin, and examined under light microscopy for the presence or absence of ganglia and inflammation. Correlation between the presence of ganglia and lower esophageal sphincter pressure was tested by Pearson's bivariant correlation. Manometry revealed three patients with hypertensive lower esophageal sphincter, four patients with nutcracker esophagus, and two patients with diffuse esophageal spasm. All three patients with a hypertensive lower esophageal sphincter revealed an absence of ganglia, whereas the six patients with nutcracker esophagus and diffuse esophageal spasm exhibited ganglia despite an elevated lower esophageal sphincter pressure in four. Hypertensive lower esophageal sphincter resembled achalasia in its absence of ganglia in Auerbach's plexus, whereas nutcracker esophagus and diffuse esophageal spasm exhibited ganglia. There was no significant correlation in our series between the presence of ganglia and an elevated lower esophageal sphincter pressure in spastic motility disorders.

Our purpose was to reassess the usefulness of barium studies and various clinical parameters for differentiating primary from secondary achalasia.

Radiology files from 1989 through 1999 revealed 29 patients with primary achalasia and 10 with secondary achalasia (caused by carcinoma of the esophagus in three, of the gastric cardia in three, of the lung in three, and of the uterus in one) who met our study criteria. The radiographs were reviewed to determine the morphologic features of the narrowed distal esophageal segment and gastric cardia and fundus. Medical records were also reviewed to determine the clinical presentation; endoscopic, manometric, and surgical findings; and treatment.

The mean patient age was 53 years in primary achalasia versus 69 years in secondary achalasia (p = 0.03). The mean duration of dysphagia was 4.5 years in primary achalasia versus 1.9 months in secondary achalasia (p <0.0001). The narrowed distal esophageal segment had a mean length of 1.9 cm in primary achalasia versus 4.4 cm in secondary achalasia (p < 0.0001), and the esophagus had a mean diameter of 6.2 cm in primary achalasia versus 4.1 cm in secondary achalasia (p <0.0001). The narrowed segment was eccentric or nodular or had abrupt proximal borders in only four of 10 patients with secondary achalasia, and evidence of tumor was present in the gastric fundus in only three.

When findings of achalasia are present on barium studies, a narrowed distal esophageal segment longer than 3.5 cm with little or no proximal dilatation in a patient with recent onset of dysphagia should be considered highly suggestive of secondary achalasia, even in the absence of other suspicious radiographic findings.

Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.

In patients with early stages of achalasia manometry is of significant diagnostic value. Technically, however, measurement of lower esophageal sphincter (LES) relaxation is not always easy. Accordingly, we looked for a simpler way of measuring incomplete LES relaxation.

In 186 consecutive patients referred to esophageal motility testing the esophageal body base-line pressure was measured during continuous swilling of 180 ml fluid within 20 sec.

Seventeen of the 186 patients had achalasia. Fourteen of these patients were compliant for the swill test, and all had a positive test, characterized by a steady increase in base-line pressure with negative deflections on deglutition. All nonachalasia patients could complete the test, which was negative in all except one patient, who had a severe peptic stricture.

The swill test is diagnostic for incomplete lower esophageal relaxation in achalasia in compliant patients without organic stenosis.

Achalasia is a disease of the oesophagus characterized by increased lower oesophageal sphincter (LOS) tone, absence of LOS relaxation with swallowing and aperistalsis of the body of the oesophagus. The aetiology and pathogenesis of idiopathic achalasia is still controversial.

We examined 16 oesophageal biopsies and one low oesophagectomy specimen from patients with achalasia. The control group was composed of five autopsy cases with no history of oesophageal disorders, three cases of diffuse oesophageal spasm, one of gastro-oesophageal reflux disease and one patient with oesophageal carcinoma. Sections were immunostained for neurofilaments NF70 and NF200, S100 protein and neurone-specific enolase. Biopsies with inflammatory infiltrates, were in addition immunostained with antibodies against leucocyte common antigen as well as for CD20, CD43, CD68 and CD45RO. All biopsies were examined after plastic embedding, and electron microscopy (EM) was performed on samples containing autonomic plexus. An inflammatory infiltrate of varying intensity was present along the nerve fascicles and around ganglion cells in 90% of the cases of achalasia. T-lymphocytes predominated in all these cases. The autonomic nerves showed loss of fibres and degenerative changes which were discernible only by EM. Although there was no convincing neuronal loss or signs of active neuronal degeneration in biopsied cases, the oesophagectomy specimen revealed total absence of neurones and significant loss of nerve fibres. The control group showed normal plexuses and no inflammation.

Degeneration and significant loss of nerve fibres associated with predominant T-cell lymphocytic inflammatory infiltrate around the myenteric plexus support the concept for the inflammatory, probably autoimmune, aetiology of autonomic nervous system injury in primary achalasia.

Although morphologic, radiographic, and manometric features of achalasia have been well defined, it has not been established by careful retrospective analysis whether achalasia is a progressive disorder resulting in complete decompensation.

To verify the hypothesis that achalasia is a progressive disease, we retrospectively investigated manometric, radiographic, and symptomatic data in patients with achalasia. Sixty-three patients (36 women and 27 men) with a median age of 44 years (range 11 to 79 years) were evaluated. The duration of symptoms ranged from 1 to 442 months, with a median of 48 months. Patients were divided into four groups according to the duration of symptoms: 36 patients with less than 5 years, 11 with 5 to 10 years, 9 with 10 to 15 years, and 7 with 15 years or more.

Contraction pressures of the esophageal body decreased significantly at every level when the duration of symptoms increased (p < 0.04). The percentage of simultaneous waves in the esophageal body rose as the duration of symptoms increased. All waves were synchronous in every patient who had had symptoms for more than 15 years. The maximal width of the esophageal body measured on esophagram became greater with an increase in the duration of symptoms, but this measurement did not reach statistical significance (p = 0.063). The tortuosity of the esophagus, measured by the maximal angle of the esophageal axis, was significantly greater in patients with a longer duration of symptoms (p < 0.02). The type of symptoms was not associated with the duration of symptoms.

Achalasia is a progressive disease, as verified by manometric and radiographic findings. The classification of esophageal motor function expressed by amplitude of contraction pressure and angle of tortuosity is objective and useful. Classification of achalasia by duration of symptoms may be important in treatment selection and effectiveness.

Idiopathic achalasia is a motility disorder of the esophagus characterized by incomplete relaxation of the lower esophageal sphincter and a loss of normal peristaltic activity in the body of the esophagus. The loss of inhibitory neurons in the distal esophagus, as well as abnormalities in the vagus nerve, dorsal motor nucleus of the vagus nerve, and autonomic nervous system, have been described in achalasia. Although the underlying cause of idiopathic achalasia is unknown, the diffuse neuronal effects found suggest a possible viral or neurodegenerative mechanism. By use of serological methods, a significant association between the HLA-DQ1 phenotype and idiopathic achalasia has been found, suggesting a possible immunogenetic mechanism. To further define immunogenetics in the pathogenesis of idiopathic achalasia, we performed tissue typing in patients with achalasia to determine their specific HLA phenotypes.

We prospectively studied 32 patients (23 white and 9 black) with idiopathic achalasia. Peripheral blood was collected, and HLA-DR and -DQ typing by polymerase chain reaction with sequence-specific primers was performed. Results were compared with those from 268 racially matched local controls.

Idiopathic achalasia and the broad HLA-DQ1 allele were not significantly associated in either population, although a trend was found in white subjects (odds ratio [OR], 2.16; chi2 = 5.36, P corrected [Pc] = 0.0824). Further subtyping in white subjects revealed a significant association between idiopathic achalasia and the DQB1*0602 allele (OR, 3.10; chi2 = 7.32, Pc = 0.0408). A strong trend was also found with the DRB1*15 allele (OR, 2.83; chi2 = 8.11, Pc = 0.0572). In the black population, there was no association between idiopathic achalasia and DQB1*0602 or DRB1*15, but a trend was found with DRB1*12 (OR, 6. 19; chi2 = 5.19, P = 0.0227 uncorrected, Pc = 0.295).

Idiopathic achalasia is associated with HLA alleles in a race-specific manner. These results support an immunogenetic mechanism in the pathogenesis of idiopathic achalasia.

Experimental and clinical evidence suggests that the loss of esophageal body function in achalasia may be a result of the outflow obstruction of a nonrelaxing, hypertensive lower esophageal sphincter. The reversibility of such abnormalities has implications to the timing of therapeutic interventions. This study was designed to evaluate the evolution and reversibility of motility abnormalities resulting from esophageal outflow obstruction in cats.

Twenty adult cats were divided into 2 groups. Group 1 consisted of 4 cats that underwent laparotomy as a sham procedure. Group 2 consisted of 16 cats that underwent surgical placement of a loose Gore-tex expanded polytetrafluoroethylene (W. L. Gore, Elkton, Md) band calibrated to 110% of the circumference of the gastroesophageal junction. The band was removed from 4 randomly selected cats each at 1, 2, 4, and 6 weeks after placement. Esophageal manometry was performed before placement of the band, at weekly intervals after placement of the band, and after removal of the band. The resting pressure and percent relaxation of the lower esophageal sphincter (LES), in addition to amplitude, duration, and propagation of esophageal body contractions, were measured at each interval. Data are expressed as median and interquartile range and compared with use of the Mann-Whitney U test for independent samples.

The LES resting pressure remained unchanged after placement of the band, but sphincter compliance was reduced, as manifested by a significant reduction in the percent of sphincter relaxation (98% prebanding, 65% postbanding, P < .05). The median amplitude of esophageal contraction decreased significantly after banding. By 6 weeks after banding the esophagus was markedly dilated and exhibited aperistaltic, low-amplitude esophageal motility typical of that seen in clinical achalasia. Importantly, removal of the bands resulted in a prompt return of both peristalsis and amplitude of contraction.

Loss of compliance of the lower esophageal sphincter produces outflow obstruction with the resultant loss of esophageal contraction amplitude and peristaltic waveform typical of achalasia in humans. These abnormalities were reversible after relief of obstruction in the feline model and may indicate that early relief of outflow obstruction in clinical achalasia may preserve esophageal function in patients.

Achalasia is a primary motor disorder of the oesophagus, in which the myenteric plexus is involved. However, abnormalities in other parts of the digestive tract have also been described in achalasia. Whether gastric myoelectrical and duodenal motor activity in these patients is also affected is unknown. Therefore, interdigestive and postprandial gastric myoelectrical and antroduodenal motor activity were studied in 11 patients with achalasia, using electrogastrography (EGG) and stationary antroduodenal manometry. Electrogastrographically, no differences were found in the gastric frequency, incidence of dysrhythmias and postprandial/fasting power ratio. In the interdigestive state a lower propagation velocity of phase III episodes was found in the achalasia patients, but other parameters were unaltered. Postprandially, no differences were found in the number of pressure waves, in the amplitude of pressure waves or in antroduodenal coordination. We conclude that gastric myoelectrical activity and antral motor activity in patients with achalasia is normal, suggesting an intact extrinsic and intrinsic neural innervation of the distal stomach. Although postprandial duodenal motility is normal, a lower propagation velocity of phase III suggests involvement of the small intestine in achalasia.

Diagnostic and therapeutic dilemmas associated with esophageal dysmotility syndromes continue to confront physicians managing these patient populations. Although modern manometric systems have allowed us to better define normal parameters of esophageal motility, with the exception of primary achalasia, the clinical relevance of many aberrant motor patterns remains unclear. The novel use of botulinum toxin in idiopathic achalasia stems from increased understanding of the pathogenesis of the disease. Similarly, as our knowledge of the pathophysiology of other esophageal motor disorders grows, in conjunction with improved diagnostic capabilities, more effective management strategies may be used in the future.

Achalasia is a motility disorder of the esophagus characterized by the loss of inhibitory neurons in the distal esophagus. Although idiopathic in nature, autoimmune mechanisms have been proposed, and we set out to determine the presence of myenteric neuronal antibodies. We prospectively studied 18 patients with well-characterized achalasia (by clinical, x-ray, and manometric evidence), nine with gastroesophageal reflux disease, and analyzed the sera from 22 disease-free controls. Using double-label, indirect immunofluorescence techniques, rat esophageal and intestinal sections were double-labeled with sera (dilutions of 1:50 to 1:400) from the three groups and with neurofilament antibody to localize neurons. Seven of 18 achalasia patients had sera that stained the majority of neurons within plexi in the esophageal and intestinal sections, including both NADPH diaphorase (nitric oxide synthase) -positive and -negative neurons. None of the gastroesophageal reflux patients or the controls showed staining. Neuronal antibodies in achalasia provide an attractive hypothesis to explain this diffuse, possibly immune-based disorder.

Achalasia is an esophageal motility disorder of unknown etiology. Several studies suggest possible herpes or measles virus etiology, but results are inconclusive. The aim of this study was to test whether herpesvirus (HV), measles (MV), or human papilloma virus (HPV) sequences could be detected in myotomy specimens from a wide spectrum of achalasia patients, using the polymerase chain reaction (PCR) technique. Myotomy specimens from 13 achalasia patients, esophagectomy specimens from nine esophageal cancer patients, and autopsy specimens from six fetuses were studied with the PCR technique. Paired oligonucleotide primers of HV (HSV-1 and 2, CMV, EBV, VZV, and HHV-6), MV and HPV sequences and exon 3 of the HPRT gene were used for the PCR DNA amplification. Amplified products were resolved on agarose gels and stained with ethidium bromide. All specimens yielded the appropriate-sized products for exon 3 of the HPRT and viral controls. No amplified products were seen in the achalasia specimens or controls corresponding to any of the virus sequences tested. The absence of HV, MV, and HPV sequences suggests that these viruses are not associated with achalasia but does not exclude the possibility of a previously unidentified virus as a causal agent. Further studies aimed at identifying an unknown viral agent as a cause for achalasia are warranted.

Benzyldimethyltetradecylammonium chloride (BAC) has previously been used to create amyenteric rat jejunal models. Fifteen opossums (D. virginiana) were injected with 10-15 mL 4 mM BAC or saline in the distal oesophagus and along with controls underwent oesophagoscopy, manometry and barium oesophagrams. Atropine and sodium nitroprusside were studied in six of the BAC-treated and five controls using oesophageal manometry. Histologically several neuronal markers, B-NADPH-diaphorase and acetylcholine esterase histochemical staining were used. NADPH-diaphorase activity was assayed at the lower oesophageal sphincter (LOS) and 3 and 5 cm above LOS in both groups. Oesophagoscopy of the treated animals showed no mucosal inflammation, or strictures. Manometrically, LOS pressures were significantly higher in the BAC-treated group (25.7 +/- 8.6 mmHg) when compared to controls (8.7 +/- 1.8 mmHg). The oesophageal contraction amplitudes were similar in both groups. While sodium nitroprusside (SNP) significantly reduced the LOS pressure, atropine did not alter the resting LOS pressure in the BAC-treated animals. Histologically at the LOS the treated group showed: (i) absence of myenteric neurons, in contrast to prominent NADPH-diaphorase and other neuron and peptide markers in the control and (ii) increase in the number of nerve bundles that were not positive for AchE. No differences were seen in the oesophageal body between the groups. The NADPH-diaphorase assay showed a significant decrease of activity in the BAC-treated LOS, but no differences in the oesophageal body compared to controls. Several of these radiologic, manometric and histological observations resemble features of achalasia and the mechanism of the tonic pressure increase at this early time point appears to be due to a non-cholinergic mechanism.

Achalasia is characterized by loss of myenteric neurons and incomplete relaxation of the lower esophageal sphincter (LES). The aim of this study was to develop an achalasia model in the opossum using the surfactant benzyldimethyltetradecylammonium chloride (BAC). This study further characterizes the achalasia model.

BAC or saline was injected circumferentially into the LES of 14 adult opossums. Eight months after injection, manometry, isolated muscle bath studies, electrical field stimulation, and histochemical analysis were performed.

Manometrically, the LES of BAC-treated opossums showed higher pressures (38.7 +/- 12 mm Hg vs. 17 +/- 3.0 mm Hg) and reduced esophageal body contraction amplitudes (4.2 +/- 3 mm Hg vs. 27.4 +/- 12 mm Hg). Isolated muscle strips challenged with carbachol and sodium nitroprusside contracted and relaxed similarly to controls. Electrical field stimulation failed to induce relaxation in BAC-treated tissue but did induce contraction. Contractile responses were markedly reduced by tetrodotoxin and atropine in BAC-treated animals and controls. An altered nitric oxide system was shown by the lack of response to L-arginine and N omega-nitro-L-arginine. Histology showed loss of myenteric neurons and increased cholinergic nerve bundles.

Loss of NO inhibitory myenteric neurons markedly reduces the relaxation of the LES, and histology and pharmacological responses suggest a proliferation of cholinergic nerves into the LES contributing to the static elevated pressures of the amyenteric LES.