Effect of secretin on lower esophageal sphincter pressure in patients with esophageal achalasia

The effect of a bolus intravenous administration of secretin (2.0 U/kg) on resting lower esophageal sphincter pressure (LESP) was investigated in seven patients with esophageal achalasia. Basal LESP before secretin injection in the patients was 60.113.4 mmHg (Mean±SEM), which was significantly higher than 26.9±2.5 mmHg in normal controls consisting of eight healthy volunteers. LESP significantly decreased within 1 min after the injection both in the patients and the controls. The maximum pressure change from each basal LESP was 31.2±5.2 mmHg in the patients, which was significantly greater than 12.1±1.8 mmHg in the controls. The effect of secretin disappeared within 5 min in the controls. The effect in the patients, however, lasted throughout the investigation time of 30 min. It is concluded that secretin has a long-acting effect on muscular relaxation of the lower esophageal sphincter in esophageal achalsia patients.     

The prevalence of autoimmune disease in patients with esophageal achalasia

Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10–15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5–19), 8.5 times as likely to have hypothyroidism (95% CI 5.0–14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9–205), 43 times as likely to have systemic lupus erythematosus (95% CI 12–154), and 259 times as likely to have uveitis (95% CI 13–1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5–5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease.     

Nonsurgical management of esophageal perforation from pneumatic dilatation in achalasia

Perforation of the esophagus is a well-described complication of pneumatic dilatation in patients with achalasia. Although successful management of these patients without surgical intervention has been reported, little follow-up data exist. We report the successful nonsurgical management of esophageal perforation after pneumatic dilatation in three patients. Manometric and radionuclide esophageal emptying studies in these patients showed satisfactory results after the dilatations despite the occurrence of perforation, and the excellent symptomatic response has been maintained during a follow-up period ranging from one to four years.     

Levels of muscle enzymes in the serum after esophageal pneumatic dilation in patients with achalasia

The success rate of pneumatic dilation of the esophagus in patients with achalasia is variable. We aim to assess whether levels of muscle enzymes in the serum are useful for predicting the efficacy of this procedure. Consecutive adults with symptomatic achalasia treated with pneumatic dilation were included. Blood samples were taken immediately before the procedure and after 12, 24 and 32 h. Clinical efficacy of the pneumatic dilation was evaluated on the basis of a symptom score defined prior to, and 2 months after the procedure. Eleven patients underwent 13 pneumatic dilations. In nine patients this was the first dilation attempt. Ten dilations were clinically effective. The study was discontinued after enzyme levels did not show a trend of increase in any of our patients. Moreover, a statistically significant unexpected decrease in creatine phosphokinase values was found 12 h after the procedure, among the 10 successful dilations. We believe that levels of muscle enzymes in the serum cannot predict the efficacy of pneumatic dilation in patients with achalasia.     

Medical treatment of esophageal achalasia

Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebocontrolled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.This work was presented in part at the 50th Annual Meeting of the American College of Gastroenterology, Miami Beach, Florida, October 1985, and published in abstract form in theAmerican Journal of Gastroenterology 80:833, 1985.     

Effect of bolus volume on proximal esophageal contractions of patients with Chagas' disease and patients with idiopathic achalasia

Chagas' disease and idiopathic achalasia patients have similar impairment of distal esophageal motility. In Chagas' disease, the contractions occurring in the distal esophageal body are similar after wet or dry swallows. Our aim in this investigation was to evaluate the effect of wet swallows and dry swallows on proximal esophageal contractions of patients with Chagas' disease and with idiopathic achalasia. We studied 49 patients with Chagas' disease, 25 patients with idiopathic achalasia, and 33 normal volunteers. We recorded by the manometric method with continuous water perfusion the pharyngeal contractions 1 cm above the upper esophageal sphincter and the proximal esophageal contractions 5 cm from the pharyngeal recording point. Each subject performed in duplicate swallows of 3‐mL and 6‐mL boluses of water and dry swallows. We measured the time between the onset of pharyngeal contractions and the onset of proximal esophageal contractions (pharyngeal‐esophageal time [PET]), and the amplitude, duration, and area under the curve (AUC) of proximal esophageal contractions. Patients with Chagas' disease and with achalasia had longer PET, lower esophageal proximal contraction amplitude, and lower AUC than controls (P≤ 0.02). In Chagas' disease, wet swallows caused shorter PET, higher amplitude, and higher AUC than dry swallows (P≤ 0.03).There was no difference between swallows of 3‐ or 6‐mL boluses. There was no difference between patients with Chagas' disease and with idiopathic achalasia. We conclude that patients with Chagas' disease and with idiopathic achalasia have a delay in the proximal esophageal response and lower amplitude of the proximal esophageal contractions.     

Pattern of esophageal eosinophilic infiltration in patients with achalasia and response to Heller myotomy and Dor fundoplication

Eosinophilic esophagitis (EoE) is now recognized as a common cause of dysphagia. Eosinophilic infiltration of the esophagus has also been associated with other conditions, such as gastroesophageal reflux disease (GERD); however, the incidence, pattern, and clinical significance of eosinophilic infiltration in achalasia are poorly documented. We sought to characterize this histological finding in patients undergoing Heller myotomy (HM) for achalasia. Ninety‐six patients undergoing laparoscopic HM for primary achalasia between 1999 and 2008 were identified from a prospective database. Serial mid and distal per‐endoscopic esophageal biopsies taken from patients before and after surgery were assessed for the presence of elevated intraepithelial eosinophils (EIEs). Slides from patients with reports suggestive of EIE were reviewed independently by two pathologists, and the highest eosinophil count/high‐power field (eos/hpf) was recorded. Dysphagia scores (0 = none to 5 = severe dysphagia), GERD health‐related quality of life scores (0 = best to 45 = worst), and 24‐hour pH results were compared before and 3 months after surgery. We related the highest eos to the symptoms and response to HM. Data are presented as median (range). Paired t‐test and Wilcoxon signed‐rank test determined significance, *P < 0.05. Of 96 patients with achalasia, 50 had undergone pre‐HM biopsies revealing EIE in 17/50 (34%), with a median of 3 eos/hpf (1–21). Two patients were found to have superimposed esophageal candidiasis. One patient met the pathologic criteria for EoE. Twenty‐five of 50 (50%) postoperative biopsies demonstrated a median of 5 eos/hpf (1–62) for a total of 28/50 patients (56%) with EIE in either the preoperative or postoperative period. Four patients (8%) met the pathologic criteria for EoE, and two demonstrated persistent esophageal candidiasis. A decrease in eosinophils was found in 6/28 patients (21%) from 3/hpf (1–21) to 0.5/hpf (0–4). Increase in eosinophils was found in 22/28 patients (79%) from 0.5/hpf (0–8) to 5/hpf (1–62). Preoperative and postoperative dysphagia scores were available in 23 patients. Dysphagia scores improved in 22/23 patients. (3 [0–5] to 0 [0–2])*. Preoperative and postoperative GERD scores were available in 21 patients. GERD scores improved in 20/21 patients (10 [3–38] to 2 [2–14])*. Four of 13 patients (30.7%) demonstrated significant reflux in the postoperative period. No difference in clinical response to HM was detected between patients with preoperative EIE compared with patients with no EIE. No correlation between postoperative esophageal pH and eos was observed. A significant number of patients with achalasia demonstrate esophageal eosinophilic infiltration even at numbers demonstrable in patients with EoE (8% 4/50). While the interaction between achalasia and esophageal eosinophilic infiltration needs further investigation, this does not represent a distinct clinical entity. Thus, the presence of esophageal eosinophils in patients presenting with dysphagia should not preclude further work‐up for other etiologies, including achalasia.     

Treatment choices and outcomes of patients with manometrically diagnosed achalasia

This prospective population‐based study was designed to evaluate treatment choices in patients with new manometrically diagnosed achalasia and their outcomes. Patients referred to the esophageal function laboratory were enrolled after a new manometric diagnosis of achalasia. Patients completed an initial achalasia symptom score validated questionnaire on their symptom severity, duration, treatment pre‐diagnosis and Medical Outcomes Study 36‐item Short‐Form (SF‐36) survey. Treatment decisions were made by the referring physician and the patient. Follow‐up questionnaires were completed every 3 months for 1 year. Patients who chose not to undergo treatment at 1‐year follow‐up completed another questionnaire after 5 years. Between January 2004 and January 2005, 83 of 124 eligible patients were enrolled. Heller myotomy was performed on 31 patients, three patients received botulinum toxin injections, and 25 patients received 29 pneumatic balloon dilatations. Twenty‐four patients chose to receive no treatment. Following treatment, patients treated with surgery, dilatation and botulinum toxin had an average improvement in achalasia symptom score of 23 +/? 12.2, 17 +/? 10.9, and 9 +/? 14, respectively. Patients receiving no treatment had worsening symptoms with a symptom score change of ?3.5 +/? 11.4. Surgery and dilatation resulted in significant improvement (P < 0.01) relative to no treatment. In univariate logistic regression, symptom severity score (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.00 to 1.08), sphincter tone (OR 1.04, 95% CI 1.00 to 1.09), difficulty swallowing liquids (OR 3.21, 95% 1.15 to 8.99), waking from sleep (OR 2.75, 95% 1.00 to 7.61), and weight loss (OR 5.99, 95% CI 1.93 to 18.58) were all significant in predicting that patients would select treatment. In the multivariate analysis, older age (OR 1.05, 95% CI 1.01 to 1.09) and weight loss (OR 3.91, 95% CI 1.02 to 15.2) were statistically significant for undergoing treatment. At 5 years, five (21%) of those who had initially declined treatment at 1 year ultimately chose a treatment. Patients who finally chose Heller myotomy had lower mental component dimension scores on the SF‐36 at 1 year than those who did not. This study shows that almost one third of patients with manometrically diagnosed achalasia choose not to undergo treatment within 1 year of their diagnosis. Patients who are more symptomatic appear to be more likely to undergo treatment by univariate analysis. In multivariate analysis, increasing age and weight loss are predictive of those who will undergo treatment, with weight loss having the greatest influence. Patients who choose not to undergo treatment make lifestyle changes to maintain their quality of life, and only a minority of them ultimately undergo treatment.     

Individual prediction of response to pneumatic dilation in patients with achalasia

During nine years, 157 consecutive patients with achalasia have been dilated in our unit. First, the long-term effect of dilation on clinical status was evaluated. The probability of being in clinical remission eight years after first dilation was 51%. The pressure of the LES measured after dilation was highly predictive of the long-term clinical evolution. Second, a predictive model of the individual response to pneumatic dilation was developed and simplified. Therapy was effective in 80% of the patients, after one to four dilations. Younger age was the only factor significantly associated with ineffective therapy. Depending on the prognosis of the outcome calculated with the predictive model, patients were classified in groups of risk that showed a different rate of ineffective therapy. In the simplified model, age 20 years, male gender, esophageal body diameter 3 cm, esophageal body basal pressure >15 mm Hg, and pressure of the lower esophageal sphincter >30 mm Hg were predictors of a poor response to dilation. We conclude that pneumatic dilation is an effective therapy for achalasia. A predictive model was useful to classify the patients in groups with a different risk for ineffective dilation. A simplification of this model could be used to predict the response to dilation.     

Compliance measurement of lower esophageal sphincter and esophageal body in achalasia and gastroesophageal reflux disease

Little is known about the effect of achalasia and gastroesophageal reflux disease (GERD) on compliance of the esophageal body and the lower esophageal sphincter (LES). Twenty-two patients with achalasia, 14 with GERD, and 14 asymptomatic volunteers were assessed. Recording apparatus consisted of a specially developed PVC bag tied to a compliance catheter, a barostat, and a polygraph. Intrabag pressures were increased incrementally while the bag volume was recorded. In each subject, pressure–volume graphs were constructed for both the esophageal body and LES and the compliance calculated. In achalasia, compliance of the esophageal body was significantly higher (P < 0.01) than in controls, whereas LES compliance was similar. Patients with GERD had a highly compliant LES in comparison to both controls and to patients with achalasia (P < 0.01 and P < 0.001, respectively); however there was no difference in their esophageal body compliance. In conclusion, foregut motility disorders can cause changes in organ compliance that are detectable using a barostat and a suitably designed compliance bag. Further measurement of compliance may provide clues to the pathogenesis of these disorders.     

Are human herpes viruses or measles virus associated with esophageal achalasia?

In order to test the hypothesis that esophageal achalasia may be due to neurotropic viral damage to the esophageal myenteric plexus, esophageal tissue with or without achalasia was analyzed by polymerase chain reaction for the presence of human herpes virus DNA or measles virus RNA. The DNA and RNA were extracted from the esophageal muscle of 12 patients with achalasia and six patients with upper esophageal carcinoma. Peripheral blood mononuclear cells from eight adult volunteers and two samples of umbilical blood mononuclear cells were also used as controls. PCR amplification with a pair of primers specific for herpes simplex type 1 and 2 viruses identified 92-bp fragments in nearly all specimens, including those without achalasia. Each 92-bp fragment was confirmed to be identical to a single herpes simplex virus sequence by automated DNA sequence analysis. No amplification for five other herpes viruses or measles virus was detected. Therefore, a specific viral etiology for achalasia was not identified in this study.     

Pneumatic dilatation in achalasia of the esophagus: a report from Argentina

We review the treatment of esophageal achalasia by means of pneumatic dilatation (PD), analyzing its results and comparing them with those of the literature. We conclude that our personal experience is similar to that of the literature: PD and surgery produce similar results (67-95%), morbidity (2-9.5%), and mortality (0.7-1%); and PD is cheaper than surgery. According to these conclusions, we believe that the decision of the appropriate treatment should be based on a combination of the choice of the properly informed patient and the operator's experience. However, we also conclude that surgery is mandatory in selected cases, such as achalasia associated with hiatus hernia, esophageal diverticula and neoplasia, history of previous PD failure (since in our experience the results after a second PD are very poor), postoperative relapse, and patients with grade IV mega-esophagus according to Resano-Malenchini's classification.     

Progression of diffuse esophageal spasm to achalasia: incidence and predictive factors

The progression of certain primary esophageal motor disorders to achalasia has been documented; however, the true incidence of this decay is still elusive. This study aims to evaluate: (i) the incidence of the progression of diffuse esophageal spasm to achalasia, and (ii) predictive factors to this progression. Thirty‐five patients (mean age 53 years, 80% females) with a manometric picture of diffuse esophageal spasm were followed for at least 1 year. Patients with gastroesophageal reflux disease confirmed by pH monitoring or systemic diseases that may affect esophageal motility were excluded. Esophageal manometry was repeated in all patients. Five (14%) of the patients progressed to achalasia at a mean follow‐up of 2.1 (range 1–4) years. Demographic characteristics were not predictive of transition to achalasia, while dysphagia (P= 0.005) as the main symptom and the wave amplitude of simultaneous waves less than 50 mmHg (P= 0.003) were statistically significant. In conclusion, the transition of diffuse esophageal spasm to achalasia is not frequent at a 2‐year follow‐up. Dysphagia and simultaneous waves with low amplitude are predictive factors for this degeneration.     

Original article: Expression of p53 as predictor for the development of esophageal cancer in achalasia patients

Patients with longstanding achalasia have an increased risk of developing esophageal cancer. Surveillance is hampered by chronic stasis. We investigated whether aberrant expressions of tumor suppressor gene p53 and proliferation marker ki67 are early predictors for progression to malignancy. In 399 achalasia patients, 4% died of esophageal cancer despite surveillance. We performed a cohort study, using surveillance biopsies from 18 patients (11 carcinoma, one high‐grade dysplasia [HGD], and six low‐grade dysplasia [LGD]) and 10 controls (achalasia patients without cancer or dysplasia development). One hundred sixty‐four biopsies were re‐evaluated and studied for p53 and ki67 expression using immunohistochemistry. Eighty‐two percent of patients with cancer/HGD showed p53 overexpression in surveillance biopsies at a mean of 6 (1–11) years prior to cancer development. In 67% of patients with LGD and only in 10% of the controls p53 overexpression was present. The proportion of samples with p53 overexpression increased with increasing grades of dysplasia. We found no difference for ki67 overexpression. p53 overexpression may identify achalasia patients at increased risk of developing esophageal carcinoma. Further study is needed to determine if patients with p53 overexpression would benefit from intensive surveillance to detect esophageal neoplasia at a potential curable stage.     

Abnormal bile flow in patients with achalasia

Background: It has been reported that esophageal achalasia is frequently associated with the dysmotility of other digestive organs. However, the prevalence of extraesophageal complications in patients with achalasia still remains poorly understood. We performed cholescintigraphy, using ^99mTc-pyridoxyl-5-methyl-tryptophan, in patients with esophageal achalasia to assess any possible dysfunction of the sphincter of Oddi associated with achalasia. Methods: Eight patients (two men and six women) were examined to determine the time required for bile to flow from the bile duct to the duodenum. Results: Excretion time of bile was markedly prolonged in five of the eight patients with achalasia. Scintigraphic findings were not correlated with the radiographic classification of achalasia or with the grading of achalasia. Conclusions: The present results suggest that a considerable number of patients with achalasia have dysfunction of the sphincter of Oddi, irrespective of the morphological type of achalasia and the grade of esophageal dilatation. Received: February 7, 2002 / Accepted: September 6, 2002 Reprint requests to: N. Uchida     

Prevalence of esophageal dysmotility in a cohort of patients with esophageal biopsies consistent with eosinophilic esophagitis

SUMMARY.  Eosinophilic esophagitis (EoE) is increasingly being diagnosed in adults presenting with dysphagia, food impactions, and chest pain. Studies to date provide conflicting data on the association of EoE and esophageal dysmotility. The objective of this study was to evaluate the prevalence of esophageal dysmotility in a cohort of patients with biopsies consistent with EoE at a military treatment facility. This is a prospective evaluation of consecutively identified patients at our institution diagnosed with EoE from March 1, 2005 to June 1, 2007. Thirty-two patients with biopsies consistent with EoE completed a symptom survey and 30 underwent esophageal manometry. The majority of EoE patients (23/30, 77%) had a normal end-expiratory lower esophageal sphincter (LES) pressure (normal range 10–35), whereas six patients had a low-normal LES pressure (6–9 mm Hg) and one patient had a decreased LES pressure (<5 mm Hg). Five patients (15.6%) were diagnosed with a nonspecific esophageal motor disorder (NSEMD). Two patients had high mean esophageal amplitude contractions >180 mm Hg (188 mm Hg, 209 mm Hg). No patient was diagnosed with nutcracker esophagus or diffuse esophageal spasm. Patients with and without NSEMD reported a similar degree of swallowing difficulty, heartburn, belching, chest pain, regurgitation, symptoms at night, and total symptom score. Likewise, eosinophil count on mucosal biopsy was similar between patients with and without a NSEMD. In this cohort, we found the prevalence of an NSEMD to be similar to that of a 10% prevalence found in a gastroesophageal reflux population.     

Delayed presentation of intrathoracic esophageal perforation after pneumatic dilation for achalasia

Pneumatic dilation （PD） is considered to be a safe and effective first line therapy for achalasia. The major adverse event caused by PD is esophageal perforation but an immediate gastrografin test may not always detect a perforation. It has been reported that delayed management of perforation for more than 24 h is associated with high mortality. Surgery is the treatment of choice within 24 h, but the management of delayed perforation remains controversial. Hereby, we report a delayed presentation of intrathoracic esophageal perforation following PD in a 48-year-old woman who suffered from achalasia. She completely recovered after intensive medical care. A review of the literature is also discussed.     

Short‐ and long‐term effects of balloon dilatation on esophageal motility in achalasia

OBJECTIVE: To explore the effect of balloon dilatation on esophageal motility in patients with achalasia. METHODS: In 48 patients diagnosed with achalasia based on clinical observations, barium radio­graphy, endoscopy and esophageal manometry, the following parameters were evaluated before dilatation, and 4 and 12?24 weeks after dilatation: symptom score, maximal width of esophagus (MWE), lower esophageal sphincter pressure (LESP), lower esophageal sphincter relaxation rate (LESRR), and contraction amplitude of esophageal body. RESULTS: The symptom score and MWE decreased significantly after dilatation (P < 0.05). The LESP decreased (P < 0.05) and LESRR increased (P < 0.05) significantly 4 weeks and 12?24 weeks after dilatation. The percentages of patients with LESP <2.67 kPa were 45.41% before dilatation, and 82.48% and 85.87% 4 weeks and 12?24 weeks after dilatation, respectively (P < 0.05). The percentages of patients with LESRR ≥80% were 6.74% before dilatation, and 55.97% and 43.78% 4 weeks and 12?24 weeks after dilatation, respectively (P < 0.05). Peristaltic waves were not observed after dilatation in any patient. CONCLUSIONS: Balloon dilatation may significantly improve the symptoms of achalasia and reduce esophageal distention by decreasing LESP and increasing LESRR. The mechanism by which balloon dilatation increases LESRR needs to be further studied.     

Utility of software analysis of esophageal manometry studies in patients with aperistalsis

Esophageal manometry is the gold standard for the diagnosis of esophageal aperistalsis. There is computer software that analyzes peristalsis on esophageal manometry, but this automated analysis has not been formally evaluated. Our primary aim was to evaluate the software analysis of esophageal aperistalsis by esophageal manometry in patients diagnosed with aperistalsis by an experienced clinician. Esophageal manometry studies from January 2006 to November 2007 were retrospectively reviewed for evidence of aperistalsis by an experienced clinician. All studies demonstrating aperistalsis were selected for further review. The automated analysis performed by our software program for each study was recorded. Agreement between the automated analysis and the clinician was measured by the proportion of agreement on the absence of peristalsis. Eighty-seven of the 962 esophageal manometry studies reviewed demonstrated aperistalsis. The automated analysis reported esophageal body peristalsis with wet swallows in 66 out of 87 patients (75.9%). In these patients, the software analyzed an average of 34.2% of the wet swallows as peristaltic. The agreement between the clinician's review and software analysis of aperistalsis was 24.1%. These data suggest there is poor agreement between the automated analysis of peristalsis and that of an experienced reviewer. Automated analysis cannot be relied upon in the diagnostic evaluation of esophageal aperistalsis as it overestimates the presence of peristalsis and may lead to incorrect diagnoses and management strategies.