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1.
Neurogastroenterol Motil ; 33(5): e14119, 2021 05.
Article En | MEDLINE | ID: mdl-33666299

Distal esophageal spasm (DES) is defined as a manometric pattern of at least 20% of premature contractions in a context of normal esophago-gastric junction relaxation in a patient with dysphagia or non-cardiac chest pain. The definition of premature contraction requires the measurement of the distal latency and identification of the contractile deceleration point (CDP). The CDP can be difficult to localize, and alternative methods are proposed. Further, it is important to differentiate contractile activity and intrabolus pressure. Multiple rapid swallows are a useful adjunctive test to perform during high-resolution manometry to search for a lack of inhibition that is encountered in DES. The clinical relevance of the DES-manometric pattern was raised as it can be secondary to treatment with opioids or observed in patients referred for esophageal manometry before antireflux surgery in absence of dysphagia and non-cardiac chest pain. Further idiopathic DES is rare, and one can argue that when encountered, it could be part of type III achalasia spectrum. Medical treatment of DES can be challenging. Recently, endoscopic treatments with botulinum toxin and peroral endoscopic myotomy have been evaluated, with conflicting results while rigorously controlled studies are lacking. Future research is required to determine the role of contractile vigor and lower esophageal sphincter hypercontractility in the occurrence of symptoms in patients with DES. The role of impedance-combined high-resolution manometry also needs to be evaluated.


Esophageal Spasm, Diffuse/diagnosis , Chest Pain/physiopathology , Deglutition Disorders/physiopathology , Esophageal Spasm, Diffuse/classification , Esophageal Spasm, Diffuse/physiopathology , Humans , Manometry , Muscle Contraction
2.
Neurogastroenterol Motil ; 33(1): e14058, 2021 01.
Article En | MEDLINE | ID: mdl-33373111

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.


Esophageal Motility Disorders/physiopathology , Manometry/methods , Esophageal Achalasia/classification , Esophageal Achalasia/diagnosis , Esophageal Achalasia/physiopathology , Esophageal Achalasia/therapy , Esophageal Motility Disorders/classification , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/therapy , Esophageal Spasm, Diffuse/classification , Esophageal Spasm, Diffuse/diagnosis , Esophageal Spasm, Diffuse/physiopathology , Esophageal Spasm, Diffuse/therapy , Esophagogastric Junction/physiopathology , Humans
3.
Am Fam Physician ; 102(5): 291-296, 2020 09 01.
Article En | MEDLINE | ID: mdl-32866357

Esophageal motility disorders can cause chest pain, heartburn, or dysphagia. They are diagnosed based on specific patterns seen on esophageal manometry, ranging from the complete absence of contractility in patients with achalasia to unusually forceful or disordered contractions in those with hypercontractile motility disorders. Achalasia has objective diagnostic criteria, and effective treatments are available. Timely diagnosis results in better outcomes. Recent research suggests that hypercontractile motility disorders may be overdiagnosed, leading to unnecessary and irreversible interventions. Many symptoms ascribed to these disorders are actually due to unrecognized functional esophageal disorders. Hypercontractile motility disorders and functional esophageal disorders are generally self-limited, and there is considerable overlap among their clinical features. Endoscopy is warranted in all patients with dysphagia, but testing to evaluate for less common conditions should be deferred until common conditions have been optimally managed. Opioid-induced esophageal dysmotility is increasingly prevalent and can mimic symptoms of other motility disorders or even early achalasia. Dysphagia of liquids in a patient with normal esophagogastroduodenoscopy findings may suggest achalasia, but high-resolution esophageal manometry is required to confirm the diagnosis. Surgery and advanced endoscopic therapies have proven benefit in achalasia. However, invasive interventions are rarely indicated for hypercontractile motility disorders, which are typically benign and usually respond to lifestyle modifications, although pharmacotherapy may occasionally be needed.


Endoscopy, Digestive System , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/therapy , Heller Myotomy/methods , Manometry , Botulinum Toxins, Type A/therapeutic use , Calcium Channel Blockers/therapeutic use , Chest Pain/physiopathology , Deglutition Disorders/physiopathology , Diagnosis, Differential , Dilatation/methods , Esophageal Achalasia/diagnosis , Esophageal Achalasia/physiopathology , Esophageal Achalasia/therapy , Esophageal Motility Disorders/physiopathology , Esophageal Spasm, Diffuse/diagnosis , Esophageal Spasm, Diffuse/physiopathology , Esophageal Spasm, Diffuse/therapy , Esophageal Stenosis/diagnosis , Esophagitis/diagnosis , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/physiopathology , Gastroesophageal Reflux/therapy , Humans , Myotomy/methods , Neuromuscular Agents/therapeutic use , Nitrates/therapeutic use
5.
Am J Gastroenterol ; 114(9): 1464-1469, 2019 09.
Article En | MEDLINE | ID: mdl-31403963

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.


Analgesics, Opioid/adverse effects , Esophageal Achalasia/chemically induced , Esophageal Spasm, Diffuse/chemically induced , Abdominal Pain/drug therapy , Adult , Aged , Analgesics, Opioid/administration & dosage , Arthralgia/drug therapy , Back Pain/drug therapy , Dose-Response Relationship, Drug , Esophageal Achalasia/physiopathology , Esophageal Diseases/chemically induced , Esophageal Diseases/physiopathology , Esophageal Spasm, Diffuse/physiopathology , Esophagogastric Junction/physiopathology , Female , Humans , Hydrocodone/administration & dosage , Hydrocodone/adverse effects , Male , Manometry , Middle Aged , Oxycodone/administration & dosage , Oxycodone/adverse effects , Retrospective Studies , Tramadol/administration & dosage , Tramadol/adverse effects
7.
Med J Malaysia ; 74(6): 540-542, 2019 12.
Article En | MEDLINE | ID: mdl-31929483

Distal oesophageal spasm is a rare condition that affects the motility of the oesophagus. It can be diagnosed by highresolution oesophageal manometry and the diagnosis is supported by other modalities such as barium swallow and esophagogastroduodenoscopy examinations. Treatment options include pharmacological therapy, endoscopy and surgical interventions. We described a case of distal oesophageal spasm in an elderly patient who presented with chronic dyspepsia.


Esophageal Spasm, Diffuse/diagnosis , Esophagus/physiopathology , Gastroesophageal Reflux/diagnosis , Heartburn/diagnosis , Aged , Diagnosis, Differential , Esophageal Spasm, Diffuse/complications , Esophageal Spasm, Diffuse/physiopathology , Humans , Male , Manometry , Pressure
8.
Curr Gastroenterol Rep ; 20(9): 42, 2018 Aug 06.
Article En | MEDLINE | ID: mdl-30079434

PURPOSE OF REVIEW: This review addresses the similarities and differences between the spastic esophageal disorders, including jackhammer esophagus, distal esophageal spasm (DES), and type III (spastic) achalasia. The pathophysiology, diagnosis, and treatment of each separate disorder are discussed herein, with an emphasis on overlapping and discordant features. RECENT FINDINGS: The Chicago Classification is a hierarchical organizational scheme for esophageal motility disorders, currently in its third iteration, with direct impact on the definitions of these three disorders. Complementary diagnostic tools such as impedance planimetry and novel manometric parameters continue to evolve. The suite of potential treatments for these disorders is also expanding, with progressive interest in the role of peroral endoscopic myotomy alongside established pharmacologic and mechanical interventions. Although jackhammer esophagus, distal esophageal spasm, and type III achalasia frequently overlap in terms of their clinical presentation and available management approaches, the divergences in their respective diagnostic criteria suggest that additional study may reveal additional mechanistic distinctions that lead in turn to further refinements in therapeutic decision-making.


Esophageal Motility Disorders/classification , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/physiopathology , Esophageal Motility Disorders/therapy , Esophageal Spasm, Diffuse/classification , Esophageal Spasm, Diffuse/diagnosis , Esophageal Spasm, Diffuse/physiopathology , Esophageal Spasm, Diffuse/therapy , Humans
9.
Am J Gastroenterol ; 112(4): 606-612, 2017 04.
Article En | MEDLINE | ID: mdl-28139656

OBJECTIVES: High-resolution manometry (HRM) is the preferred method for the evaluation of motility disorders. Recently, an update of the diagnostic criteria (Chicago 3.0) has been published. The aim of this study was to compare the performance criteria of Chicago version 2.0 (CC2.0) vs. 3.0 (CC3.0) in a cohort of healthy volunteers and symptomatic patients. METHODS: HRM studies of asymptomatic and symptomatic individuals from several centers of Spain and Latin America were analyzed using both CC2.0 and CC3.0. The final diagnosis was grouped into hierarchical categories: obstruction (achalasia and gastro-esophageal junction obstruction), major disorders (distal esophageal spasm, absent peristalsis, and jackhammer), minor disorders (failed frequent peristalsis, weak peristalsis with small or large defects, ineffective esophageal motility, fragmented peristalsis, rapid contractile with normal latency and hypertensive peristalsis) and normal. The results were compared using McNemar's and Kappa tests. RESULTS: HRM was analyzed in 107 healthy volunteers (53.3% female; 18-69 years) and 400 symptomatic patients (58.5% female; 18-90 years). In healthy volunteers, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 7.5% and 5.6%, respectively, major disorders in 1% and 2.8%, respectively, minor disorders in 25.2% and 15%, respectively, and normal in 66.4% and 76.6%, respectively. In symptomatic individuals, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 11% and 11.3%, respectively, major disorders in 14% and 14%, respectively, minor disorders in 33.3% and 24.5%, respectively, and normal in 41.8% and 50.3%, respectively. In both groups of individuals, only an increase in normal and a decrease in minor findings using CC3.0 were statistically significant using McNemar's test. DISCUSSIONS: CC3.0 increases the number of normal studies when compared with CC2.0, essentially at the expense of fewer minor disorders, with no significant differences in major or obstructive disorders. As the relevance of minor disorders is questionable, our data suggest that CC3.0 increases the relevance of abnormal results.


Esophageal Achalasia/diagnosis , Esophageal Spasm, Diffuse/diagnosis , Manometry , Adolescent , Adult , Aged , Case-Control Studies , Esophageal Achalasia/classification , Esophageal Achalasia/physiopathology , Esophageal Diseases/classification , Esophageal Diseases/diagnosis , Esophageal Diseases/physiopathology , Esophageal Motility Disorders/classification , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/physiopathology , Esophageal Spasm, Diffuse/classification , Esophageal Spasm, Diffuse/physiopathology , Esophagogastric Junction/physiopathology , Female , Healthy Volunteers , Humans , Latin America , Male , Middle Aged , Peristalsis/physiology , Spain , Young Adult
10.
Abdom Radiol (NY) ; 42(3): 985-986, 2017 Mar.
Article En | MEDLINE | ID: mdl-27832322

Corkscrew esophagus (also referred as rosary bead esophagus) is a classic finding of diffuse esophageal spasm (DES) in barium studies reflecting abnormal contractions, leading to compartmentalization and curling of the esophagus, ultimately giving an appearance similar to a corkscrew or rosary beads. We review the pathophysiology of this finding, correlating it to corkscrew and rosary images that originated this classic description.


Esophageal Spasm, Diffuse/diagnostic imaging , Esophageal Spasm, Diffuse/physiopathology , Barium Sulfate , Contrast Media , Diagnosis, Differential , Humans , Manometry
11.
Neurogastroenterol Motil ; 28(8): 1186-93, 2016 08.
Article En | MEDLINE | ID: mdl-27018150

BACKGROUND: In the past, ambulatory 24-h manometry has been shown useful for the evaluation of patients with non-cardiac chest pain (NCCP). With the diagnostic improvements brought by pH-impedance monitoring and high-resolution manometry (HRM), the contribution of ambulatory 24-h manometry to the diagnosis of esophageal hypertensive disorders has become uncertain. Our aim was to assess the additional diagnostic yield of ambulatory manometry to HRM and ambulatory pH-impedance monitoring in this patient population. METHODS: All patients underwent 24-h ambulatory pressure-pH-impedance monitoring and HRM. Patients had retrosternal pain as a predominant symptom and no explanation after cardiologic and digestive endoscopic evaluations. Diagnostic measurements were analyzed by two independent physicians. KEY RESULTS: Fifty-nine patients met the inclusion criteria; 37.3% of the patients had their symptoms explained by abnormalities on pH-impedance monitoring and 6.8% by ambulatory manometry. Functional chest pain was diagnosed in 52.5% of the patients. High-resolution manometry, using the Chicago Classification v3.0 criteria alone, did not identify any of the four patients with esophageal spasm on ambulatory manometry. However, taking into account other abnormalities, such as simultaneous (rapid) or repetitive contractions, HRM had a sensitivity of 75% and a specificity of 98.2% for the diagnosis of esophageal spasm. CONCLUSIONS & INFERENCES: In the work-up of NCCP, ambulatory 24-h manometry has a low additional diagnostic yield. However, it remains the best technique to identify esophageal spasm as the cause of symptoms. This is particularly useful when an unequivocal diagnosis is needed before treatment.


Chest Pain/diagnosis , Esophageal Spasm, Diffuse/diagnosis , Esophagus/physiopathology , Gastroesophageal Reflux/diagnosis , Aged , Chest Pain/physiopathology , Esophageal Spasm, Diffuse/physiopathology , Female , Gastroesophageal Reflux/physiopathology , Humans , Male , Manometry , Middle Aged , Sensitivity and Specificity
12.
Neurogastroenterol Motil ; 28(2): 260-5, 2016 Feb.
Article En | MEDLINE | ID: mdl-26553751

BACKGROUND: According to the Chicago classification of esophageal motility disorders, distal esophageal spasm (DES) is defined as premature esophageal contractions (distal latency [DL] <4.5 s) for ≥20% of swallows, in the presence of a normal mean integral relaxation pressure (IRP). However, some patients with symptoms of DES have rapid contractions with a normal DL. The aim of this study was to characterize these patients and compare their clinical characteristics to those of patients classified as DES. METHODS: We retrospectively compared clinical characteristics and high-resolution manometry findings of patients with rapid contractions with normal latency to those meeting the Chicago classification criteria for DES. KEY RESULTS: Over a 3-year period, nine patients were diagnosed with DES and 14 showed rapid contractions in the distal esophagus with normal latency. The latter were younger than DES patients (60 ± 4 vs 72 ± 3 years, p < 0.05). Dysphagia and retrosternal pain occurred to a similar degree in both groups. Weight loss and abnormal barium esophagogram tended to be more frequent in DES patients. There was no difference in contractile front velocity (CFV) and in distal contractile integral (DCI) between patients with DES and rapid contractions with normal latency. Lower esophageal sphincter pressures were not different between groups. However, IRP was significantly higher in DES compared to rapid contractions with normal latency (11.7 ± 0.6 mmHg vs 7.6 ± 1.2 mmHg, p < 0.05), albeit still within the normal range. CONCLUSIONS & INFERENCES: These data suggest that patients with simultaneous contractions with normal latency represent a group of patients with many features similar to DES.


Esophageal Spasm, Diffuse/diagnosis , Esophageal Spasm, Diffuse/physiopathology , Esophagus/physiopathology , Aged , Female , Humans , Male , Manometry , Middle Aged , Retrospective Studies
14.
Ter Arkh ; 87(4): 36-40, 2015.
Article Ru | MEDLINE | ID: mdl-26087632

AIM: To comparatively analyze clinical manifestations in patients with primary esophageal spasm (ES) and its concurrence with gastroesophageal reflux disease (GERD) and the results of their instrumental examinations and psychodiagnostic tests. SUBJECTS AND METHODS: A total of 104 patients with the clinical and manometric signs of ES were examined and divided into two groups: 1) 42 patients with primary ES; 2) 62 patients with ES concurrent with GERD. The examination encompassed esophageal manometry, esophagogastroduodenoscopy, 24-hour pH metry, and an interview using a questionnaire to identify autonomic disorders, and the Mini-Mult test. RESULTS: The patients with primary ES compared to those with ES concurrent with GERD significantly more frequently showed severe pain syndrome (p = 0.009) and a paradoxical dysphagia pattern (p = 0.03); manometry revealed an incoordination in the motility of the entire esophagus (p = 0.001). Comparison of the statistical series of values for contraction amplitude and duration in the distal esophagus found no significant difference in the patients of both groups. Autonomic disturbances were detected in 76.0% of the patients with ES; but the intergroup differences were insignificant. Mental maladaptation was observed in 81.7% of the patients in the absence of intergroup differences. CONCLUSION: The etiopathogenetic factor of ES is a psychoautonomic response to chronic stress in both primary ES and its concurrence with GERD. The reflux of gastric contents into the esophagus does not appear to be one of the leading causes of ES. In primary ES, esophageal motor function is generally impaired to a much greater extent than that in ES concurrent with GERD. The degree of motor disorders is embodied in the specific clinical features of the disease.


Esophageal Spasm, Diffuse/physiopathology , Esophagus/physiopathology , Endoscopy, Digestive System , Esophageal Spasm, Diffuse/etiology , Esophageal Spasm, Diffuse/metabolism , Esophageal pH Monitoring , Esophagus/metabolism , Female , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/physiopathology , Humans , Hydrogen-Ion Concentration , Male , Manometry , Pressure
15.
Curr Opin Gastroenterol ; 31(4): 328-33, 2015 Jul.
Article En | MEDLINE | ID: mdl-26039725

PURPOSE OF REVIEW: Distal esophageal spasm (DES) is a rare esophageal motility disorder associated with dysphagia and chest pain. In 2011, the diagnosis of DES was refined based on the occurrence of premature (rather than rapid) contractions by high-resolution manometry. New therapeutic options have also been recently proposed. Thus, a review on DES incorporating publications since 2012 is timely because of these revisions in definition and management. RECENT FINDINGS: DES remains a heterogeneous clinical disorder. Its pathophysiology is still debated and DES might be related to achalasia. Alternatively, it might be secondary to medications, especially opiates. Endoscopic ultrasound might be informative diagnostically by demonstrating muscularis propria hypertrophy and thickening. Botulinum toxin injection in the esophageal body has been shown superior to placebo to relieve symptoms associated with DES. Finally, per oral endoscopic myotomy is a promising therapeutic approach, but may be less effective in DES than in achalasia. SUMMARY: The diagnosis of DES should lead to a systematic search for medication that might promote the occurrence of esophageal dysmotility. Endoscopic treatment of DES (botulinum toxin injection or per oral endoscopic myotomy) should be further evaluated in controlled studies using current diagnostic criteria by high-resolution manometry.


Esophageal Spasm, Diffuse/diagnosis , Esophageal Spasm, Diffuse/therapy , Botulinum Toxins/therapeutic use , Endosonography/methods , Esophageal Spasm, Diffuse/etiology , Esophageal Spasm, Diffuse/physiopathology , Esophageal Sphincter, Lower/surgery , Esophagus/physiopathology , Humans , Manometry/methods , Natural Orifice Endoscopic Surgery/methods , Neurotoxins/therapeutic use
19.
Tunis Med ; 92(7): 488-92, 2014 Jul.
Article Fr | MEDLINE | ID: mdl-25775289

BACKGROUND: Diffuse esophageal spasms is a primary motor disrder of the esophagus of unknown etiology characterized by intermettent peristalsis. This is rare condition which represents 3-5% if primary disorders of the esophagus. Diagnosis and treatment of this entity are difficult. AIMS: To evaluate the frequency and the clinical and the manometric features of diffuse esophageal spasms. METHODS: We conducted a retrospective study related to esophageal manometry performed between January 2000 and December 2011 regardless of the indication. Patients with meeting criteria for diffuse esophageal spasms (> 20 % simultaneous waves with greater than 30 mmHg pressure in the esophagus) were included. RESULTS: Out of 1188 patients, 13 (1,09 %) met the manometric criteria for diffuse esophageal spasms. It was 8 women and 5 men with a median age of 57 years. Dysphagia was the most relevant symptom and chest pain was only noted in 1 patient. The frequency of simultaneous waves was between 20 and 80 %. The pressure of the lower esophageal sphincter was normal in most cases. CONCLUSION: In this Tunisian manometric study, the diffuse esophageal spasms is rare. Dysphagia was the most relevant symptom and the pressure of the lower esophageal sphincter was normal in most cases.


Esophageal Spasm, Diffuse/physiopathology , Adolescent , Adult , Aged , Female , Humans , Male , Manometry , Middle Aged , Retrospective Studies , Young Adult
20.
Dis Esophagus ; 26(5): 470-4, 2013 Jul.
Article En | MEDLINE | ID: mdl-22816880

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.


Esophageal Achalasia/physiopathology , Esophageal Spasm, Diffuse/physiopathology , Deglutition Disorders/etiology , Disease Progression , Esophageal Achalasia/complications , Esophageal Spasm, Diffuse/complications , Esophageal pH Monitoring , Female , Follow-Up Studies , Heartburn/etiology , Humans , Male , Manometry , Middle Aged , Predictive Value of Tests , Risk Factors
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