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Provenza CG, Romanelli JR. Achalasia: Diagnosis and Management. Surg Clin North Am 2025; 105:143-158. [PMID: 39523069 DOI: 10.1016/j.suc.2024.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Achalasia is an incurable condition of the esophagus involving the inflammation and degeneration of inhibitory neurons of the lower esophageal sphincter (LES) resulting in failure of the LES to relax. Typical symptoms of achalasia are dysphagia, retrosternal chest pain, regurgitation, and weight loss. Three studies are typically required for the diagnosis of achalasia: barium swallow, high-resolution esophageal manometry, and esophagogastroduodenoscopy. Differential diagnosis includes gastroesophageal reflux disease, pseudoachalasia, neoplasm, and nonachalasia esophageal motility disorders such as scleroderma, jackhammer esophagus, distal esophageal spasm, and nutcracker esophagus.
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Affiliation(s)
- Christina G Provenza
- University of Massachusetts Chan Medical School, Baystate Medical Center, Springfield, MA, USA
| | - John Robert Romanelli
- University of Massachusetts Chan Medical School, Baystate Medical Center, Springfield, MA, USA.
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Di Brina ALP, Palmieri O, Cannarozzi AL, Tavano F, Guerra M, Bossa F, Gentile M, Merla A, Biscaglia G, Cuttitta A, Perri F, Latiano A. Focus on Achalasia in the Omics Era. Int J Mol Sci 2024; 25:10148. [PMID: 39337632 PMCID: PMC11431880 DOI: 10.3390/ijms251810148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 09/17/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Achalasia is a rare and complex esophageal disease of unknown etiology characterized by difficulty in swallowing due to the lack of opening of the lower esophageal sphincter and the absence of esophageal peristalsis. Recent advancements in technology for analyzing DNA, RNA and biomolecules in high-throughput techniques are offering new opportunities to better understand the etiology and the pathogenetic mechanisms underlying achalasia. Through this narrative review of the scientific literature, we aim to provide a comprehensive assessment of the state-of-the-art knowledge on omics of achalasia, with particular attention to those considered relevant to the pathogenesis of the disease. The notion and importance of the multi-omics approach, its limitations and future directions are also introduced, and it is highlighted how the integration of single omics data will lead to new insights into the development of achalasia and offer clinical tools which will allow early diagnosis and better patient management.
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Affiliation(s)
- Anna Laura Pia Di Brina
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Orazio Palmieri
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Anna Lucia Cannarozzi
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Francesca Tavano
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Maria Guerra
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Fabrizio Bossa
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Marco Gentile
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Antonio Merla
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Giuseppe Biscaglia
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Antonello Cuttitta
- Unit of Thoracic Surgery, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy;
| | - Francesco Perri
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
| | - Anna Latiano
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; (A.L.P.D.B.); (O.P.); (A.L.C.); (F.T.); (M.G.); (F.B.); (M.G.); (A.M.); (G.B.); (F.P.)
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Abu Suleiman A, James D, Wilkins A, Bladel AV, Lo T. Achalasia-associated megaoesophagus presenting with dyspnoea and cough. BMJ Case Rep 2024; 17:e258950. [PMID: 38367990 PMCID: PMC10875499 DOI: 10.1136/bcr-2023-258950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2024] Open
Abstract
We present an unusual case of achalasia presenting with dyspnoea and persistent cough. These symptoms persisted for months, leading to the patient undergoing a chest X-ray by her general practitioner which showed right basal consolidation and a density extending along the right mediastinum. CT scan was done which revealed megaoesophagus with a diameter of 7 cm causing tracheal compression, as well as right basal consolidation, consistent with aspiration. Further history revealed 6-month history of progressive swallowing difficulty, retrosternal chest pain and shortness of breath which worsened when eating solid foods. After thorough workup, a diagnosis of idiopathic achalasia (type II) was made. She was treated with laparoscopic Heller cardiomyotomy and Dor fundoplication with significant improvement at follow-up. Dyspnoea and respiratory symptoms are unusual presenting symptoms, suggesting a need to consider achalasia in a wider range of presentations. Successful treatment of achalasia depends on timely diagnosis and intervention prior to oesophageal failure.
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Affiliation(s)
- Amro Abu Suleiman
- Department of Upper Gastrointestinal Surgery, Hull University Teaching Hospitals NHS Trust, Cottingham, UK
| | - Daniel James
- Department of Upper Gastrointestinal Surgery, Hull University Teaching Hospitals NHS Trust, Cottingham, UK
| | - Alexander Wilkins
- Department of Upper Gastrointestinal Surgery, Hull University Teaching Hospitals NHS Trust, Cottingham, UK
| | - Adrian Van Bladel
- Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Terence Lo
- Department of Upper Gastrointestinal Surgery, Hull University Teaching Hospitals NHS Trust, Cottingham, UK
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Bahdi F, Labora A, Shah S, Farooq M, Wangrattanapranee P, Donahue T, Issa D. From Scalpel to Scope: How Surgical Techniques Made Way for State-of-The-Art Endoscopic Procedures. GASTRO HEP ADVANCES 2023; 3:370-384. [PMID: 39131137 PMCID: PMC11307641 DOI: 10.1016/j.gastha.2023.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 10/30/2023] [Indexed: 08/13/2024]
Abstract
The continuous evolution of endoscopic tools over the years has paved the way for minimally invasive alternatives to surgical procedures for multiple gastrointestinal conditions. While few endoscopic techniques have supplanted their surgical counterparts like percutaneous gastrostomy tubes, many have emerged as noninferior, less morbid alternatives for such diverse conditions as achalasia (peroral endoscopic myotomy), obesity (endoscopic sleeve gastroplasty), drainage of pancreatic walled off necrosis (EUS-guided cystogastrostomy), and gastric outlet obstruction (EUS-guided gastrojejunostomy). These techniques were based on surgical concepts and would not have been feasible without collaboration between surgeons and endoscopists. Such collaboration is exemplified by the antireflux fundoplication, which features combined hiatal hernia repair with transoral and incisionless fundoplication. The burgeoning armamentarium of endoscopic alternatives to traditional surgical procedures requires a multidisciplinary discussion and individually tailored treatment plans that consider patient preferences as well as the relative risks and benefits of surgical and endoscopic approaches. As technological advances give rise to ever more innovative endoscopic techniques, studies to evaluate clinical outcomes and define their role in treatment algorithms will be required.
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Affiliation(s)
- Firas Bahdi
- Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Amanda Labora
- Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Sagar Shah
- Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Maryam Farooq
- David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Peerapol Wangrattanapranee
- Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Timothy Donahue
- Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Danny Issa
- Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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Kim Y, Shibli F, Fu Y, Song G, Fass R. Multiple Sclerosis Is Associated With Achalasia and Diffuse Esophageal Spasm. J Neurogastroenterol Motil 2023; 29:478-485. [PMID: 37528077 PMCID: PMC10577467 DOI: 10.5056/jnm22173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 04/12/2023] [Accepted: 04/12/2023] [Indexed: 08/03/2023] Open
Abstract
Background/Aims Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are both disorders of esophageal peristalsis which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES. Methods Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts. Patients with a prior diagnosis of diabetes mellitus, chronic Chagas' disease, opioid use, or CREST syndrome were excluded from the study. Results Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; P < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; P < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms. Conclusions Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.
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Affiliation(s)
- Yeseong Kim
- Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Fahmi Shibli
- Division of Gastroenterology and Hepatology, The Esophageal and Swallowing Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Yuhan Fu
- Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Gengqing Song
- Division of Gastroenterology and Hepatology, The Esophageal and Swallowing Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, The Esophageal and Swallowing Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
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Khaiser A, Baig M, Forcione D, Bechtold M, Puli SR. Efficacy and Safety of Peroral Endoscopic Myotomy (POEM) in Achalasia: An Updated Meta-analysis. Middle East J Dig Dis 2023; 15:235-241. [PMID: 38523886 PMCID: PMC10955992 DOI: 10.34172/mejdd.2023.352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 07/06/2023] [Indexed: 03/26/2024] Open
Abstract
Background: Heller myotomy has been considered the standard surgical treatment for patients with achalasia. Since the initiation of peroral endoscopic myotomy (POEM), it has represented an alternative for treating patients with achalasia. Over the years, numerous prospective and retrospective studies with POEM use for achalasia have been published. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of POEM in patients with achalasia. Methods: Publications investigating the safety and efficacy of POEM in patients with achalasia were searched in Medline, Ovid Journals, Medline non-indexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects models. Results: The initial search identified 328 reference articles; of these, 34 relevant articles were selected and reviewed. Data was extracted from 20 studies (n=1753) which met the inclusion criteria. In pooled analysis, the clinical success of POEM at 3 months was 94% (95% CI=93-95). The pooled clinical success of POEM at 12 months was 91% (95% CI=90-92). The pooled rate of gastroesophageal reflux disease (GERD) was 21% (95% CI=19-23), esophagitis was reported in 16% (95% CI=15-18), pneumomediastinum in 4% (95% CI=3-6), cervical emphysema in 12% (95% CI=10-13), pneumoperitoneum in 8% (95% CI=7-10), pneumothorax in 5% (95% CI=4 - 6), pleural effusion in 3% (95% CI=2-3), post-operative bleeding in 4.29% (95% CI=1.91 -7.61) and aspiration pneumonia in 3.08% (95% CI=1.13-5.97) of the patients after POEM. Conclusion: This meta-analysis suggests that POEM is a highly effective and safe endoscopic treatment for patients with achalasia and a reasonable alternative to Heller myotomy.
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Affiliation(s)
- Afshin Khaiser
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
| | - Muhammad Baig
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
| | - David Forcione
- Department of Gastroenterology and Hepatology, Boca Raton Regional Hospital, Boca Raton, FL, USA
| | - Matthew Bechtold
- Department of Gastroenterology and Hepatology, University of Missouri-Columbia, Columbia, MO, USA
| | - Srinivas R. Puli
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
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Blonski W, Slone S, Richter JE. Update on the Diagnosis and Treatment of Achalasia. Dysphagia 2023; 38:596-608. [PMID: 35585208 DOI: 10.1007/s00455-022-10435-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 03/04/2022] [Indexed: 12/23/2022]
Abstract
Achalasia is a rare disease of the esophagus with impaired relaxation of the lower esophageal sphincter and aperistalsis. The etiology is unknown but speculations include a viral or autoimmune etiology. All specialists dealing with swallowing and esophageal diseases should recognize the classic symptoms of dysphagia for solids/liquids, regurgitation, and choking, especially at night. High-resolution manometry is critical for the diagnosis with endoscopy and barium esophagram having a supportive role. The disease cannot be cured but most can return to near normal swallowing and a regular diet with appropriate therapy. Treatment includes smooth muscle relaxants, botulinum toxin injections to the lower sphincter, pneumatic dilation, Heller myotomy, and peroral endoscopic myotomy. One treatment does not fit all and a tailored approach through a multidiscipline team will give the best long-term outcomes.
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Affiliation(s)
- Wojciech Blonski
- Division of Gastroenterology, James A. Haley VA Hospital, Tampa, FL, USA
- Division of Gastroenterology and Nutrition, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 72, Tampa, FL, 33612, USA
| | - Samuel Slone
- Division of Gastroenterology and Nutrition, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 72, Tampa, FL, 33612, USA
| | - Joel E Richter
- Division of Gastroenterology and Nutrition, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 72, Tampa, FL, 33612, USA.
- Joy McCann Culverhouse Center for Esophageal Diseases, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
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Ribolsi M, Andrisani G, Di Matteo FM, Cicala M. Achalasia, from diagnosis to treatment. Expert Rev Gastroenterol Hepatol 2023; 17:21-30. [PMID: 36588469 DOI: 10.1080/17474124.2022.2163236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Achalasia is an uncommon esophageal motility disorder and is characterized by alterations of the motility of the esophageal body in conjunction with altered lower esophageal sphincter (LES) relaxation. The clinical presentation of patients with achalasia may be complex; however, the most frequent symptom is dysphagia. The management of patients with achalasia is often challenging, due to the heterogeneous clinical presentation. AREAS COVERED The diagnosis and management of achalasia has significantly improved in the last years due to the growing availability of high-resolution manometry (HRM) and the implementation in the therapeutic armamentarium of new therapeutic endoscopic procedures. Traditional therapeutic strategies include botulinum toxin injected to the LES and pneumatic balloon dilation. On the other hand, surgical treatments contemplate laparoscopic Heller myotomy and, less frequently, esophagectomy. Furthermore, in the last few years, per oral endoscopic myotomy (POEM) has been proposed as the main endoscopic therapeutic alternative to the laparoscopic Heller myotomy. EXPERT OPINION Diagnosis and treatment of achalasia still represent a challenging area. However, we believe that an accurate up-front evaluation is, nowadays, necessary in addressing patients with achalasia for a more accurate diagnosis as well as for the best treatment options.
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Affiliation(s)
- Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | | | | | - Michele Cicala
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
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Savarino E, Bhatia S, Roman S, Sifrim D, Tack J, Thompson SK, Gyawali CP. Achalasia. Nat Rev Dis Primers 2022; 8:28. [PMID: 35513420 DOI: 10.1038/s41572-022-00356-8] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/01/2022] [Indexed: 02/07/2023]
Abstract
Achalasia is a rare disorder of the oesophageal smooth muscle characterized by impaired relaxation of the lower oesophageal sphincter (LES) and absent or spastic contractions in the oesophageal body. The key pathophysiological mechanism is loss of inhibitory nerve function that probably results from an autoimmune attack targeting oesophageal myenteric nerves through cell-mediated and, possibly, antibody-mediated mechanisms. Achalasia incidence and prevalence increase with age, but the disorder can affect all ages and both sexes. Cardinal symptoms consist of dysphagia, regurgitation, chest pain and weight loss. Several years can pass between symptom onset and an achalasia diagnosis. Evaluation starts with endoscopy to rule out structural causes, followed by high-resolution manometry and/or barium radiography. Functional lumen imaging probe can provide complementary evidence. Achalasia subtypes have management and prognostic implications. Although symptom questionnaires are not useful for diagnosis, the Eckardt score is a simple symptom scoring scale that helps to quantify symptom response to therapy. Oral pharmacotherapy is not particularly effective. Botulinum toxin injection into the LES can temporize symptoms and function as a bridge to definitive therapy. Pneumatic dilation, per-oral endoscopic myotomy and laparoscopic Heller myotomy can provide durable symptom benefit. End-stage achalasia with a dilated, non-functioning oesophagus may require oesophagectomy or enteral feeding into the stomach. Long-term complications can, rarely, include oesophageal cancer, but surveillance recommendations have not been established.
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Affiliation(s)
- Edoardo Savarino
- Gastroenterology Unit, Azienda Ospedale Università di Padova (AOUP), Padua, Italy. .,Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Padua, Italy.
| | - Shobna Bhatia
- Department of Gastroenterology, Sir HN Reliance Foundation Hospital, Mumbai, India
| | - Sabine Roman
- Hospices Civils de Lyon, Digestive Physiology, Hopital E Herriot, Lyon, France.,Université Lyon 1, Villeurbanne, France.,Inserm U1032, LabTAU, Lyon, France
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK
| | - Jan Tack
- Division of Gastroenterology, University Hospital of Leuven, Leuven, Belgium
| | - Sarah K Thompson
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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10
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Sanaka MR, Garg R, Chadalavada P, Thota PN, Gabbard S, Parikh MP, Khoudari G, Murthy S, Raja S. Peroral Endoscopic Myotomy Is Safe and Highly Effective Treatment for Advanced Achalasia With Sigmoid Esophagus. J Clin Gastroenterol 2021; 55:505-511. [PMID: 32649445 DOI: 10.1097/mcg.0000000000001388] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 06/02/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS In advanced achalasia patients with sigmoid esophagus, peroral endoscopic myotomy (POEM) might be technically challenging and its outcomes are not well known in western population. Hence, our study aims were to assess and compare the safety and efficacy of POEM in achalasia patients with and without sigmoid esophagus. MATERIALS AND METHODS Medical records of achalasia patients who had POEM at our institution between April 2014 and December 2019 were reviewed. Patients who underwent work-up comprising timed barium esophagram (TBE) and high-resolution esophageal manometry (HREM) before POEM along with 2-month post-POEM esophageal pH study, TBE and HREM were included in the final analysis. Patients were categorized as either sigmoid or no sigmoid esophagus based on the morphology of esophagus on TBE as per Japan Esophageal Society guidelines. Treatment success was defined as reduction of post-POEM Eckardt score to ≤3. RESULTS A total of 168 patients (sigmoid esophagus=20; no sigmoid esophagus=148) were included. Esophageal width on TBE at 1 minute was significantly higher in sigmoid esophagus group compared with no sigmoid esophagus group (4.9 vs. 3.0 cm, P<0.001). Procedural outcomes and complications were similar in both groups. At 2-month follow-up, both groups had significant improvement in Eckardt scores, TBE, and HREM parameters. Treatment success was high and similar in both sigmoid and no sigmoid groups (94.4% vs. 93.2%, P=0.84). The rates of gastroesophageal reflux disease were also similar in both groups. CONCLUSIONS Our study findings suggest that POEM is safe and highly effective treatment for achalasia patients with sigmoid esophagus similar to those without sigmoid esophagus in western population. POEM should be considered as the treatment of choice in advanced achalasia with sigmoid esophagus.
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Affiliation(s)
| | | | | | | | | | | | | | - Sudish Murthy
- Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH
| | - Siva Raja
- Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH
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Abstract
Peroral endoscopic myotomy surgery is an incisionless, minimally invasive, natural orifice technique used to treat the symptoms of achalasia and other spastic disorders of the esophagus. Recent experience demonstrates that it can be performed safely by experienced esophageal surgeons and there are very good short-term outcomes comparable to laparoscopic myotomy. The rapid worldwide adoption of this technique demonstrates its potential to replace the current therapies available for achalasia. A cautionary note is important in that long-term outcomes are not yet available in terms of dysphagia and GERD symptoms.
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Affiliation(s)
- Lara W Schaheen
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, UPMC Presbyterian, Suite C-800, 200 Lothrop Street, Pittsburgh, PA 15213, USA
| | - Manuel Villa Sanchez
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, UPMC Presbyterian, Suite C-800, 200 Lothrop Street, Pittsburgh, PA 15213, USA
| | - James D Luketich
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, UPMC Presbyterian, Suite C-800, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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12
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An original Eurasian haplotype, HLA-DRB1*14:54-DQB1*05:03, influences the susceptibility to idiopathic achalasia. PLoS One 2018; 13:e0201676. [PMID: 30092016 PMCID: PMC6084941 DOI: 10.1371/journal.pone.0201676] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 07/19/2018] [Indexed: 01/04/2023] Open
Abstract
Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (pC<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.
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Genetic Predisposition and Effect of Race in Achalasia. Am J Med Sci 2018; 355:101. [DOI: 10.1016/j.amjms.2017.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 12/14/2017] [Accepted: 12/18/2017] [Indexed: 11/21/2022]
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Gockel HR, Lesse M, Schumacher J, Müller M, Gockel I. Esophagus-Related Symptoms in First-Degree Relatives of Patients with Achalasia: Is Screening Necessary? Visc Med 2016; 32:369-374. [PMID: 27921050 DOI: 10.1159/000445790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Despite an increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia, its association with well-defined genetic syndromes, the candidate gene approach, and recent presentation of the first systematic genome-wide association study on achalasia suggest the involvement of genetic factors. METHODS In this study we analyzed the frequency with which symptoms associated with esophageal function (swallowing difficulties, regurgitations, retrosternal cramps/pain, heartburn) occur in first-degree relatives of patients with achalasia to determine if screening is useful and justified against the background of early diagnosis in a genetically predisposed population. The survey of data was carried out in 759 relatives of the 359 achalasia patients included in this study by means of structured interviews. RESULTS Swallowing difficulties as the principal symptom of achalasia were found to occur at least occasionally in 11.2% of first-degree relatives. In comparison with the prevalence of dysphagia in the general population of 7-10% up to 22%, as described in the literature, the frequency of swallowing difficulties does not seem to be increased in our population of relatives. CONCLUSION Screening measures do not appear to be justified in spite of the potential genetic background of achalasia.
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Affiliation(s)
- Henning R Gockel
- Institute of Human Genetics, Life and Brain, University of Bonn, Bonn, Germany
| | - Moritz Lesse
- Clinic of Internal Medicine, Dr. Horst Schmidt-Klinik (HSK Helios-Klinik), Wiesbaden, Germany
| | - Johannes Schumacher
- Institute of Human Genetics, Life and Brain, University of Bonn, Bonn, Germany
| | - Michaela Müller
- Department of Gastroenterology, German Clinic for Diagnostics (DKD Helios-Klink), Wiesbaden, Germany
| | - Ines Gockel
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
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Abstract
Achalasia is a primary disorder of esophageal motility. It classically presents with dysphagia to both solids and liquids but may be accompanied by regurgitation and chest pain. The gold standard for the diagnosis of achalasia is esophageal motility testing with manometry, which often reveals aperistalsis of the esophageal body and incomplete lower esophageal sphincter relaxation. The diagnosis is aided by complimentary tests, such as esophagogastroduodenoscopy and contrast radiography. Esophagogastroduodenoscopy is indicated to rule out mimickers of the disease known as “pseudoachalasia” (eg, malignancy). Endoscopic appearance of a dilated esophagus with retained food or saliva and a puckered lower esophageal sphincter should raise suspicion for achalasia. Additionally, barium esophagography may reveal a dilated esophagus with a distal tapering giving it a “bird’s beak” appearance. Multiple therapeutic modalities aid in the management of achalasia, the decision of which depends on operative risk factors. Conventional treatments include medical therapy, botulinum toxin injection, pneumatic dilation, and Heller myotomy. The last two are defined as the most definitive treatment options. New emerging therapies include peroral endoscopic myotomy, placement of self-expanding metallic stents, and endoscopic sclerotherapy.
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Affiliation(s)
- Joseph T Krill
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Rishi D Naik
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, TN, USA
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Sodikoff JB, Lo AA, Shetuni BB, Kahrilas PJ, Yang GY, Pandolfino JE. Histopathologic patterns among achalasia subtypes. Neurogastroenterol Motil 2016; 28:139-45. [PMID: 26542087 PMCID: PMC4688144 DOI: 10.1111/nmo.12711] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/24/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns. METHODS 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. KEY RESULTS 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). CONCLUSIONS & INFERENCES 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.
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Affiliation(s)
- Jamie B Sodikoff
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611
| | - Amy A Lo
- Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611
| | - Brandon B Shetuni
- Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611
| | - Peter J Kahrilas
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611
| | - John E Pandolfino
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611
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17
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Abstract
Idiopathic achalasia is a primary esophageal motor disorder characterized by loss of esophageal peristalsis and insufficient lower esophageal sphincter relaxation in response to deglutition. Patients with achalasia commonly complain of dysphagia to solids and liquids, bland regurgitation often unresponsive to an adequate trial of proton pump inhibitor, and chest pain. Weight loss is present in many, but not all patients. Although the precise etiology is unknown, it is often thought to be either autoimmune, viral immune, or neurodegenerative. The diagnosis is based on history of the disease, barium esophagogram, and esophageal motility testing. Endoscopic assessment of the gastroesophageal junction and gastric cardia is necessary to rule out malignancy. Newer diagnostic modalities such as high resolution manometry help in predicting treatment response in achalasia based on esophageal pressure topography patterns identifying three phenotypes of achalasia (I-III) and outcome studies suggest better treatment response with types I and II compared to type III. Although achalasia cannot be permanently cured, excellent outcomes are achieved in over 90 % of patients. Current medical and surgical therapeutic options (pneumatic dilation, endoscopic and surgical myotomy, and pharmacologic agents) aim at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Either graded pneumatic dilatation or laparoscopic surgical myotomy with a partial fundoplication are recommended as initial therapy guided by patient age, gender, preference, and local institutional expertise. The prognosis in achalasia patients is excellent. Most patients who are appropriately treated have a normal life expectancy but the disease does recur and the patient may need intermittent treatment.
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Affiliation(s)
| | - Hannah P Kim
- Department of Internal Medicine, Nashville, TN, USA
| | | | - Michael F Vaezi
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA.
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18
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Ates F, Vaezi MF, Fox M, Gyawali CP, Roman S, Smout AJPM, Pandolfino JE. The Pathogenesis and Management of Achalasia: Current Status and Future Directions. Gut Liver 2015; 9:449-63. [PMID: 26087861 PMCID: PMC4477988 DOI: 10.5009/gnl14446] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Achalasia is an esophageal motility disorder that is commonly misdiagnosed initially as gastroesophageal reflux disease. Patients with achalasia often complain of dysphagia with solids and liquids but may focus on regurgitation as the primary symptom, leading to initial misdiagnosis. Diagnostic tests for achalasia include esophageal motility testing, esophagogastroduodenoscopy and barium swallow. These tests play a complimentary role in establishing the diagnosis of suspected achalasia. High-resolution manometry has now identified three subtypes of achalasia, with therapeutic implications. Pneumatic dilation and surgical myotomy are the only definitive treatment options for patients with achalasia who can undergo surgery. Botulinum toxin injection into the lower esophageal sphincter should be reserved for those who cannot undergo definitive therapy. Close follow-up is paramount because many patients will have a recurrence of symptoms and require repeat treatment.
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Affiliation(s)
| | - Michael F. Vaezi
- Correspondence to: Michael F. Vaezi, Division of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, C2104-MCN, Nashville, TN 37232, USA, Tel: +1-615-322-3739, Fax: +1-615-322-8525, E-mail:
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Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study. J Immunol Res 2015; 2015:729217. [PMID: 26078981 PMCID: PMC4452860 DOI: 10.1155/2015/729217] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 03/24/2015] [Accepted: 04/14/2015] [Indexed: 02/08/2023] Open
Abstract
Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.
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Cuttitta A, Tancredi A, Andriulli A, De Santo E, Fontana A, Pellegrini F, Scaramuzzi R, Scaramuzzi G. Fundoplication after heller myotomy: a retrospective comparison between nissen and dor. Eurasian J Med 2015; 43:133-40. [PMID: 25610181 DOI: 10.5152/eajm.2011.31] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2011] [Accepted: 10/24/2011] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE A retrospective comparison between Nissen and Dor fundoplication after laparoscopic Heller myotomy for achalasia. MATERIALS AND METHODS From 1998 to 2004 a first group of 48 patients underwent Heller myotomy and Nissen fundoplication for idiopathic achalasia (H+N group). From 2004 to 2010 a second group of 40 patients underwent Heller myotomy followed by Dor fundoplication (H+D group). Some patients received a previous endoscopic treatment with pneumatic dilatation or endoscopic injection of botulinum toxin that provided them only a temporary clinical benefit. Changes in clinical and instrumental examinations from before to after surgery were evaluated in all patients. Clinical evaluation was carried out using a modified DeMeester symptom score system. RESULTS Dor fundoplication treatment reduced both dysphagia and regurgitation severity scores significantly more than Nissen fundoplication (p<0.0001). Indeed, the incidence of dysphagia was significantly higher in patients treated with floppy-Nissen than in those treated with Dor fundoplication: by defining dysphagia as a DeMeester score equal to 3 (arbitrary cut-off), at the end of follow-up dysphagia occurred in 17.65% and 0% (p=0.037) of patients belonging to the H+N and H+D groups, respectively. CONCLUSION Heller myotomy followed by Dor fundoplication is a safe and valuable treatment. The procedure showed a lower incidence of postoperative dysphagia versus Nissen fundoplication and a negligible incidence of postoperative GERD in a long-term postoperative follow-up.
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Affiliation(s)
- Antonello Cuttitta
- Unit of General Surgery 2 and Thoracic Surgery, IRCCS "Casa Sollievo della Soff erenza" Hospital, Viale Cappuccini, San Giovanni Rotondo, FG, Italy
| | - Antonio Tancredi
- Unit of General Surgery 2 and Thoracic Surgery, IRCCS "Casa Sollievo della Soff erenza" Hospital, Viale Cappuccini, San Giovanni Rotondo, FG, Italy ; PhD School in Internal Medicine and Medical Therapy, Department of Internal Medicine and Medical Therapy, University of Pavia, Piazzale Golgi, Pavia, PV, Italy
| | - Angelo Andriulli
- Unit of Gastroenterology, IRCCS "Casa Sollievo della Soff erenza" Hospital, Viale Cappuccini, San Giovanni Rotondo, FG, Italy
| | - Ermelinda De Santo
- Unit of Gastroenterology, IRCCS "Casa Sollievo della Soff erenza" Hospital, Viale Cappuccini, San Giovanni Rotondo, FG, Italy
| | - Andrea Fontana
- Unit of Biostatistics, IRCCS "Casa Sollievo della Soff erenza" Hospital-Viale Cappuccini, San Giovanni Rotondo, FG, Italy
| | - Fabio Pellegrini
- Unit of Biostatistics, IRCCS "Casa Sollievo della Soff erenza" Hospital-Viale Cappuccini, San Giovanni Rotondo, FG, Italy ; Laboratory of Clinical Epidemiology of Diabetes and Chronic Diseases, Consorzio Mario Negri Sud-Via Nazionale, Santa Maria Imbaro, CH, Italy
| | - Roberto Scaramuzzi
- Unit of General Surgery 2 and Thoracic Surgery, IRCCS "Casa Sollievo della Soff erenza" Hospital, Viale Cappuccini, San Giovanni Rotondo, FG, Italy ; Graduate School of Medicine, Catholic University of the Sacred Heart - Largo Francesco Vito, Rome, Italy
| | - Gerardo Scaramuzzi
- Unit of General Surgery 2 and Thoracic Surgery, IRCCS "Casa Sollievo della Soff erenza" Hospital, Viale Cappuccini, San Giovanni Rotondo, FG, Italy
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Kim E, Lee H, Jung HK, Lee KJ. Achalasia in Korea: an epidemiologic study using a national healthcare database. J Korean Med Sci 2014; 29:576-80. [PMID: 24753707 PMCID: PMC3991803 DOI: 10.3346/jkms.2014.29.4.576] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2013] [Accepted: 02/10/2014] [Indexed: 12/20/2022] Open
Abstract
Owing to the rarity of the disease, epidemiologic information on achalasia is limited. This study aimed to investigate the epidemiology and treatment patterns of achalasia in the population of Korea using a national healthcare database. The diagnostic code K22.0 of the International Classification of Diseases was used to identify cases of achalasia between 2007 and 2011. Treatment modalities for achalasia were identified using the electronic data interchange codes Q7642 or Q7641 for balloon dilation and QA421 or QA422 for esophago-cardiomyotomy. A total of 3,105 patients with achalasia (1,447 men; mean age, 52.5 yr) were identified between 2007 and 2011, indicating a prevalence of 6.29/100,000 (95% confidence interval [CI], 4.94-7.66) during this 5-yr period. A total of 191 incident cases of achalasia (82 men; mean age, 49.5 yr), which were not diagnosed as achalasia in the previous 4 yr, were detected in 2011, indicating an incidence of 0.39/100,000 (95% CI, 0.15-0.63) for that year. During the study period, balloon dilation therapy was performed a total of 975 times in 719 patients, and surgical esophago-cardiomyotomy was performed once per patient in 17 patients. This is the first population-based epidemiologic study of achalasia in Korea.
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Affiliation(s)
- Eunkyung Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Hongsub Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Hye-kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
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Bredenoord AJ, Rösch T, Fockens P. Peroral endoscopic myotomy for achalasia. Neurogastroenterol Motil 2014; 26:3-12. [PMID: 24304406 DOI: 10.1111/nmo.12257] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Accepted: 10/06/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND Treatment of achalasia is complicated by symptom recurrence and a significant risk for severe complications. Endoscopic myotomy was developed in the search for a highly efficacious treatment with lower risks. Since its introduction in 2010, several centers have adopted the technique and published excellent short-term results of open label series. Randomized trials with long-term endpoint comparing per-oral endoscopic myotomy (POEM) with the established treatments such as balloon dilation and surgical myotomy are now warranted, before POEM can be regarded as the routine clinical care for achalasia patients. PURPOSE This review describes the development, technical aspects, efficacy, and complications of POEM.
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Affiliation(s)
- A J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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Sayles M, Harrison L, McGlashan JA, Grant DG. Zenker's diverticulum complicating achalasia: a 'cup-and-spill' oesophagus. BMJ Case Rep 2013; 2013:bcr-2013-200702. [PMID: 24334471 DOI: 10.1136/bcr-2013-200702] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 72-year-old woman presented with long-standing gastro-oesophageal reflux, regurgitation of swallowed food and worsening cervical dysphagia. Fluoroscopic barium oesophagography revealed a posterolateral pharyngeal pouch (Zenker's diverticulum (ZD)) complicating a 'cup and spill' oesophageal deformity with a smoothly tapered segment at the gastro-oesophageal junction. CT and high-resolution manometry confirmed that the underlying abnormality was a massively dilated oesophagus with aperistalsis and pan-oesophageal pressurisation, consistent with a diagnosis of oesophageal achalasia (type II). She underwent endoscopic stapled diverticulotomy, with good symptomatic relief. We discuss the aetiology of ZD, its management and the association here with oesophageal achalasia.
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Affiliation(s)
- Mark Sayles
- Department of Otolaryngology-Head and Neck Surgery, Nottingham University Hospitals NHS Trust, Nottingham, UK
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Sarnelli G, D’Alessandro A, Pesce M, Palumbo I, Cuomo R. Genetic contribution to motility disorders of the upper gastrointestinal tract. World J Gastrointest Pathophysiol 2013; 4:65-73. [PMID: 24244875 PMCID: PMC3829454 DOI: 10.4291/wjgp.v4.i4.65] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 08/09/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
Motility disorders of the upper gastrointestinal tract encompass a wide range of different diseases. Esophageal achalasia and functional dyspepsia are representative disorders of impaired motility of the esophagus and stomach, respectively. In spite of their variable prevalence, what both diseases have in common is poor knowledge of their etiology and pathophysiology. There is some evidence showing that there is a genetic predisposition towards these diseases, especially for achalasia. Many authors have investigated the possible genes involved, stressing the autoimmune or the neurological hypothesis, but there is very little data available. Similarly, studies supporting a post-infective etiology, based on an altered immune response in susceptible individuals, need to be validated. Further association studies can help to explain this complex picture and find new therapeutic targets. The aim of this review is to summarize current knowledge of genetics in motility disorders of the upper gastrointestinal tract, addressing how genetics contributes to the development of achalasia and functional dyspepsia respectively.
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Quidute ARP, Freitas EVD, Lima TGD, Feitosa AML, Santos JPD, Correia JW. Achalasia and thyroid disease: possible autoimmune connection? ACTA ACUST UNITED AC 2013; 56:677-82. [PMID: 23329193 DOI: 10.1590/s0004-27302012000900013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2012] [Accepted: 10/02/2012] [Indexed: 02/14/2023]
Abstract
Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition.
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The management of esophageal achalasia: from diagnosis to surgical treatment. Updates Surg 2013; 66:23-9. [PMID: 23817763 DOI: 10.1007/s13304-013-0224-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Accepted: 06/21/2013] [Indexed: 02/07/2023]
Abstract
The goal of this review is to illustrate our approach to patients with achalasia in terms of preoperative evaluation and surgical technique. Indications, patient selection and management are herein discussed. Specifically, we illustrate the pathogenetic theories and diagnostic algorithm with current up-to-date techniques to diagnose achalasia and its manometric variants. Finally, we focus on the therapeutic approaches available today: medical and surgical. A special emphasis is given on the surgical treatment of achalasia and we provide the reader with a detailed description of our pre and postoperative management.
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Torab FC, Hamchou M, Ionescu G, Al-Salem AH. Familial achalasia in children. Pediatr Surg Int 2012; 28:1229-33. [PMID: 23076455 DOI: 10.1007/s00383-012-3186-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/01/2012] [Indexed: 12/22/2022]
Abstract
Achalasia is rare in the pediatric age group and in most cases it is idiopathic with no family history. Familial achalasia is very rare. This report describes two families with achalasia: in one, six children were affected while in the other a brother and a sister had Allgrove's syndrome (triple-A syndrome consisting of achalasia, adrenal insufficiency, and alacrima). Familial achalasia suggests that it is hereditary and may be transmitted as an autosomal recessive trait. The management of achalasia in children is still controversial. With the recent advances in minimal invasive surgery, laparoscopic Heller's myotomy is the procedure of choice in the management of achalasia in children.
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Affiliation(s)
- Fawaz Chikh Torab
- Division of Pediatric Surgery, Department of Surgery, Tawam Hospital, Al-Ain, Abu Dhabi, United Arab Emirates.
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Ghoshal UC, Daschakraborty SB, Singh R. Pathogenesis of achalasia cardia. World J Gastroenterol 2012; 18:3050-7. [PMID: 22791940 PMCID: PMC3386318 DOI: 10.3748/wjg.v18.i24.3050] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2011] [Revised: 10/11/2011] [Accepted: 04/28/2012] [Indexed: 02/06/2023] Open
Abstract
Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down’s syndrome and Parkinson’s disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.
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Bagheri R, Haghi SZ, Noorshafiee S. Surgical treatment of achalasia: transabdominal versus transthoracic cardiomyotomy. Ann Thorac Cardiovasc Surg 2011; 17:254-9. [PMID: 21697786 DOI: 10.5761/atcs.oa.09.01506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2009] [Accepted: 05/27/2010] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Achalasia is a primary esophageal motor disorder involving the body of the esophagus and lower esophageal sphincter. The mechanism is destruction of the myenteric plexus after a viral infection. Multiple methods of treatment with variable results induced in achalasia. MATERIALS AND METHODS We analyzed 70 patients with achalasia that underwent surgical treatment with transabdominal or transthoracic cardiomyotomy from 1982 to 2008 in Mashhad (Ghaem and Omid) hospital and at least 2 years follow up for evaluated result of surgery. RESULTS The mean age was 39.2 ± 9.42 years and the M/F = 0.89. The most common symptom was dysphagia (100%). The interval between beginnings of symptoms to a definitive diagnosis was 10.6 ± 8.3 month. The ratio between the two techniques was 35/35 = 1. In 67.1% of patients, a previous history of pneumatic dilation was reported. Long-term good results after surgery were seen in 77.2% of patients. Recurrence after surgical treatment was seen in 22.8%. A comparison of the two techniques (with or without antireflux surgery), showed a greater failure rate in transabdominal cardiomyotomy without the antireflux protocol (8/15 = 40%), but by the chi- square test, the difference was not statistically significant (P = 0.107). The most common complication after surgery was esophageal leakage (2.85%), and mortality was zero. In recurrence, most patients underwent pneumatic dilation (9/16 = 56.2%), and if surgery was needed, all patients underwent a transthoracic approach with antireflux treatment. CONCLUSION Based on the good, long-term results with the surgical treatment of achalasia, surgery is recommended in most patients. A transthoracic or transabdominal approach had good, long-term results, but a transthoracic approach had better results and usually did not need antireflux surgery.
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Affiliation(s)
- Reza Bagheri
- Thoracic Surgery, Mashhad University of Medical Sciences, Ahmad Abad Street, Mashhad, Iran.
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Nuñez C, García-González MA, Santiago JL, Benito MS, Mearín F, de la Concha EG, de la Serna JP, de León AR, Urcelay E, Vigo AG. Association of IL10 promoter polymorphisms with idiopathic achalasia. Hum Immunol 2011; 72:749-52. [PMID: 21641950 DOI: 10.1016/j.humimm.2011.05.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Revised: 04/18/2011] [Accepted: 05/13/2011] [Indexed: 12/21/2022]
Abstract
Idiopathic achalasia is an esophageal motor disorder of unknown etiology. A wealth of evidence supports the concept that achalasia is an immune-mediated disease. According to this evidence, achalasia has been significantly associated with specific alleles of the human leukocyte antigen class II, PTPN22 and IL23R. Several studies have demonstrated association of the IL10 gene with different inflammatory disorders. Our aim was to evaluate the role of functional IL10 promoter polymorphisms in susceptibility to idiopathic achalasia. A case-control study was performed with the -1082, -819, and -592 IL10 promoter polymorphisms in 282 patients and 529 controls and in an independent replication set of 75 patients and 575 controls. The GCC haplotype of the IL10 promoter was reported to be associated with a lower risk of achalasia in the discovery sample (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.64-0.98, p = 0.029). This association was validated in a replication set (OR = 0.69, 95% CI = 0.48-1.00, p = 0.04). In the combined analysis no heterogeneity was observed between the 2 sample sets and the GCC haplotype was significantly associated with the disease (OR(MH) = 0.76, 95% CI = 0.63-0.91, p = 0.003). Our results provide the first evidence for an association between IL10 promoter polymorphisms and idiopathic achalasia, suggesting that the interleukin-10 cytokine may contribute to the pathogenesis of this disease.
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Affiliation(s)
- Concepción Nuñez
- Clinical Immunology Department, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain
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Abstract
Several theories on the etiology and pathophysiology of achalasia have been reported but, to date, it is widely accepted that loss of peristalsis and absence of swallow-induced relaxation of the lower esophageal sphincter are the main functional abnormalities. Treatment of achalasia often aims to alleviate the symptoms of achalasia and not to correct the underlying disorder. Medical therapy has poor efficacy, so patients who are good surgical candidates should be offered either laparoscopic myotomy or pneumatic balloon dilatation. Their own preference should be included in the decision-making process, and treatment should meet the local expertise with these procedures. Laparoscopic surgical esophagomyotomy is a safe and effective modality. It can be considered as initial management or as secondary treatment if the patient does not respond to less invasive modalities. Pneumatic dilatation has proven to be a safe, effective, and durable modality of treatment when performed by experienced individuals, and appears to be the most cost-effective alternative. For patients with multiple comorbidities and for elderly patients, who are not good surgical candidates, endoscopic injection of botulinum toxin should be considered a safe and effective procedure. However, its positive effect diminishes over time, and the need for multiple repeated sessions must be taken into consideration. In the management of patients with achalasia, nutritional aspects play an important role. When lifestyle changes are insufficient, it is necessary to proceed to percutaneous gastrostomy under radiological guidance. In the future, intraluminal myotomy or endoscopic mucosectomy will possibly be an option. Further studies are needed to investigate the role of immunosuppressive therapies in those cases in which an autoimmune etiology is suspected.
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Affiliation(s)
| | | | | | - Fabio Cisarò
- Gastroenterology and Hepatology Unit, Department of Medicine, San Giovanni Battista Hospital, Torino, Italy
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Gockel HR, Schumacher J, Gockel I, Lang H, Haaf T, Nöthen MM. Achalasia: will genetic studies provide insights? Hum Genet 2010. [PMID: 20700745 DOI: 10.1007/s00439-010-0874-8.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Despite increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia and its association with well-defined genetic syndromes suggest the involvement of genetic factors. Mutant mouse models display gastrointestinal disturbances that are similar to those observed in achalasia patients. The candidate gene approach has revealed some promising results; however, it has not established conclusive links to specific genes so far. The aim of this review was to summarize current knowledge of the genetics of achalasia. We also discuss the extent to which our understanding of achalasia is likely to be enhanced through future molecular genetic research.
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Affiliation(s)
- Henning R Gockel
- Department of General and Abdominal Surgery, Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany
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Gockel HR, Schumacher J, Gockel I, Lang H, Haaf T, Nöthen MM. Achalasia: will genetic studies provide insights? Hum Genet 2010; 128:353-64. [PMID: 20700745 DOI: 10.1007/s00439-010-0874-8] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2010] [Accepted: 08/02/2010] [Indexed: 12/15/2022]
Abstract
Despite increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia and its association with well-defined genetic syndromes suggest the involvement of genetic factors. Mutant mouse models display gastrointestinal disturbances that are similar to those observed in achalasia patients. The candidate gene approach has revealed some promising results; however, it has not established conclusive links to specific genes so far. The aim of this review was to summarize current knowledge of the genetics of achalasia. We also discuss the extent to which our understanding of achalasia is likely to be enhanced through future molecular genetic research.
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Affiliation(s)
- Henning R Gockel
- Department of General and Abdominal Surgery, Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany
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Affiliation(s)
- Dawn L Francis
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
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35
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de León AR, de la Serna JP, Santiago JL, Sevilla C, Fernández-Arquero M, de la Concha EG, Nuñez C, Urcelay E, Vigo AG. Association between idiopathic achalasia and IL23R gene. Neurogastroenterol Motil 2010; 22:734-8, e218. [PMID: 20367798 DOI: 10.1111/j.1365-2982.2010.01497.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Idiopathic achalasia is a primary esophageal motor disorder of unknown etiology. Different evidences have been reported in support of achalasia as the result of an autoimmune and inflammatory process leading to neuronal cell loss. According to this, idiopathic achalasia has been significantly associated with specific alleles of the human leukocyte antigen system class II, although few reports studying association with other loci can be found in the literature. Recent studies have shown association of a non-synonymous polymorphism within the IL23R gene with different chronic inflammatory disorders, including Barrett's esophagus. The purpose of this study was to assess whether the IL23R coding variant Arg381Gln polymorphism is involved in susceptibility to idiopathic achalasia. METHODS We performed a case-control study including 262 patients with idiopathic achalasia and 802 healthy subjects, all of them white Spaniards. Achalasia patients were diagnosed on the basis of clinical, radiographic, endoscopic, and manometric criteria. All samples were genotyped for the IL23R Arg381Gln polymorphism using TaqMan technology. KEY RESULTS The minor allele of the Arg381Gln polymorphism was significantly increased in patients compared with healthy controls (OR = 1.46, 95% CI = 1.01-2.11, P = 0.036). This association seems to be specific to male patients with disease onset after 40 years (OR = 2.33, 95% CI = 1.29-4.16, P = 0.002). CONCLUSIONS & INFERENCES Our results suggest a role of IL23R in idiopathic achalasia predisposition and extend the evidence of the general influence of this gene in autoimmune and inflammatory diseases.
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Affiliation(s)
- A R de León
- Gastroenterology Department, Hospital Clínico San Carlos, Madrid, Spain
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Roll GR, Rabl C, Ciovica R, Peeva S, Campos GM. A controversy that has been tough to swallow: is the treatment of achalasia now digested? J Gastrointest Surg 2010; 14 Suppl 1:S33-45. [PMID: 19760373 PMCID: PMC2825313 DOI: 10.1007/s11605-009-1013-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2009] [Accepted: 08/25/2009] [Indexed: 01/31/2023]
Abstract
Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the lower esophageal sphincter that presents within a spectrum of disease severity related to progressive pathological changes, most commonly resulting in dysphagia. The pathophysiology of achalasia is still incompletely understood, but recent evidence suggests that degeneration of the postganglionic inhibitory nerves of the myenteric plexus could be due to an infectious or autoimmune mechanism, and nitric oxide is the neurotransmitter affected. Current treatment of achalasia is directed at palliation of symptoms. Therapies include pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic dilation, and surgery. Until the late 1980s, endoscopic dilation was the first line of therapy. The advent of safe and effective minimally invasive surgical techniques in the early 1990s paved the way for the introduction of laparoscopic myotomy. This review will discuss the most up-to-date information regarding the pathophysiology, diagnosis, and treatment of achalasia, including a historical perspective. The laparoscopic Heller myotomy with partial fundoplication performed at an experienced center is currently the first line of therapy because it offers a low complication rate, the most durable symptom relief, and the lowest incidence of postoperative gastroesophageal reflux.
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Affiliation(s)
- Garrett R. Roll
- Department of Surgery, University of Wisconsin, School of Medicine and Public Health, 600 Highland Avenue, H4/744 CSC, Madison, WI 53792-7375 USA
| | - Charlotte Rabl
- Department of Surgery, University of Wisconsin, School of Medicine and Public Health, 600 Highland Avenue, H4/744 CSC, Madison, WI 53792-7375 USA
| | - Ruxandra Ciovica
- Department of Surgery, University of Wisconsin, School of Medicine and Public Health, 600 Highland Avenue, H4/744 CSC, Madison, WI 53792-7375 USA
| | - Sofia Peeva
- Department of Surgery, University of Wisconsin, School of Medicine and Public Health, 600 Highland Avenue, H4/744 CSC, Madison, WI 53792-7375 USA
| | - Guilherme M. Campos
- Department of Surgery, University of Wisconsin, School of Medicine and Public Health, 600 Highland Avenue, H4/744 CSC, Madison, WI 53792-7375 USA
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Paladini F, Cocco E, Cascino I, Belfiore F, Badiali D, Piretta L, Alghisi F, Anzini F, Fiorillo MT, Corazziari E, Sorrentino R. Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene. Neurogastroenterol Motil 2009; 21:597-602. [PMID: 19309439 DOI: 10.1111/j.1365-2982.2009.01284.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio-pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti-inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.
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Affiliation(s)
- F Paladini
- Department of Cell Biology and Development, Sapienza University of Rome, Rome, Italy
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Abstract
Esophageal dysphagia can arise from a variety of causes such as motility disorders, mechanical and inflammatory diseases. Adequate management includes a detailed history, evaluation with upper endoscopy, barium radiography and manometry. Treatment is usually tailored to the underlying disease process and in some cases, as in inoperable cancer, palliative management may be necessary.
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Affiliation(s)
- Adeyemi Lawal
- Medical College of Wisconsin, Department of Medicine, Division of Gastroenterology and Hepatology, Froedtert East, FEC-4510, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
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39
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Abstract
Achalasia is the best understood and most readily treatable esophageal motility disorder. It serves as a prototype for disorders of the enteric nervous system with degeneration of the myenteric neurons that innervate the lower esophageal sphincter (LES) and esophageal body. Investigations into the pathogenesis have highlighted the importance of nitric oxide and the possible role of an autoimmune response to a viral insult in genetically susceptible individuals. Advances in diagnostic testing have delineated manometric variants of achalasia that have implications for management. Treatment studies have demonstrated the limited efficacy of botulinum toxin as well as less than ideal, long-term effectiveness of both pneumatic dilation and Heller myotomy. This article incorporates these recent developments into the current understanding of achalasia.
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Affiliation(s)
- Natasha Walzer
- Division of Gastroenterology, Northwestern University Feinberg School of Medicine, 676 North Saint Clair Street, Suite 1400, Chicago, IL 60611-3008, USA
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40
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Abstract
Achalasia, a motor disorder of the esophagus, is characterized by myenteric plexitis leading to neuronal loss. Cytotoxic T cells, isolated from the lower esophageal sphincter of achalasia patients, respond to human herpes virus-1 (HSV-1) with gamma-IFN (and to a lesser extent IL-2) production and clonal proliferation. In addition, HSV-1 DNA was demonstrated in the vast majority of patients, but also in controls. These exciting data suggest that achalasia is an immune-mediated inflammatory disease in which a (latent) infection with HSV-1 leads to persistent immune activation and self-destruction of esophageal neurons, most likely in genetic susceptible subjects only.
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41
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Esophagus Benign Diseases of the Esophagus. Surgery 2008. [DOI: 10.1007/978-0-387-68113-9_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Gender-specific association of the PTPN22 C1858T polymorphism with achalasia. Hum Immunol 2007; 68:867-70. [DOI: 10.1016/j.humimm.2007.07.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2007] [Revised: 07/20/2007] [Accepted: 07/30/2007] [Indexed: 12/20/2022]
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Abstract
Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES) relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg) is present in most but not in all patients. Heartburn occurs in 27%-42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram), and esophageal motility testing (esophageal manometry). Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients.
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Affiliation(s)
- Farnoosh Farrokhi
- Division of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Michael F Vaezi
- Division of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Abstract
AIM: To investigate some possible etiologies of achalasia by screening patients with achalasia for some autoimmune diseases such as thyroid disease.
METHODS: We examined 30 known cases of achalasia (20 females, 10 males). Their age ranged 15-70 years. All of them were referred to our institute for treatment. Their sera were evaluated to detect some possible associations with rheumatoid disease, thyroid disease, inflammatory process, anemia, etc.
RESULTS: Seven out of 30 patients (23%) had thyroid disease including four patients with hypothyroidism (13.3%), two patients with hyperthyroidism (6.6%), and one had only thyroid nodule but was in euthyroid state (3.3%). Two of these hypothyroid patients had no related clinical symptoms (subclinical) and two had clinical manifestations of hypothyroidism. There were no correlations between the intensity of thyroid diseases and the severity of achalasia symptoms.
CONCLUSION: The etiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. Thyroid disease presents concomitantly with achalasia in about one fourth of our patients who may have a common etiology.
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Affiliation(s)
- Mohammad Hassan Emami
- Isfahan University of Medical Sciences, Poursina Hakim Research Institution, Isfahan, Iran
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45
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Abstract
Esophageal achalasia is an infrequent motility disorder characterized by a progressive stasis and dilation of the oesophagus; with subsequent risk of aspiration, weight loss, and malnutrition. Although the treatment of achalasia has been traditionally based on a surgical approach, especially with the introduction of laparoscopic techniques, there is still some space for a medical approach. The present article reviews the non-surgical therapeutic options for achalasia.
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Mearin F, García-González MA, Strunk M, Zárate N, Malagelada JR, Lanas A. Association between achalasia and nitric oxide synthase gene polymorphisms. Am J Gastroenterol 2006; 101:1979-84. [PMID: 16848803 DOI: 10.1111/j.1572-0241.2006.00762.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Our group previously reported the absence of nitric oxide synthase (NOS) in the gastroesophageal junction of patients with achalasia. NOS exists in three distinct isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible isoform (iNOS). Some studies have shown that NO production is regulated by NOS polymorphisms. AIM To assess whether some functional polymorphisms in the nNOS, iNOS, or eNOS genes are involved in susceptibility to suffer from achalasia. METHODS Genomic DNA from 80 unrelated Spanish Caucasian patients with sporadic achalasia and 144 healthy subjects matched for age (+/-5 yr) and gender was typed by PCR and RFLP methods for the 27-bp variable number of tandem repeat (VNTR) polymorphism in intron 4 of the eNOS gene, a CA microsatellite repeat and a Nla III (C-->T) restriction fragment length polymorphism (RFLP) in exon 29 of the nNOS gene, and two nucleotide substitutions located in exon 16 (C-->T) and exon 22 (G-->A) of the iNOS gene. RESULTS No significant differences in carriage, genotype, and allele frequencies of the nNOS, iNOS, or eNOS gene polymorphisms were found between patients with achalasia and controls. Individuals homozygous for genotype iNOS22*A/A tended to be more frequent in achalasia (20%vs 11%, odds ratio [OR] 1.79, 95% confidence interval [CI] 0.89-3.59, p= 0.09) as were those homozygous for the rare eNOS*4a allele (6.2%vs 1.4%, OR 4.5, 95% CI 0.89-22.67, p= 0.1) although the difference did not reach statistical significance. No differences in genotype and allele distribution were found with respect to epidemiological and clinical characteristics of patients with achalasia. CONCLUSION Our data suggest that NOS gene polymorphisms are not involved in the susceptibility to and nature of the clinical course of sporadic achalasia. However, studies in a greater number of patients are required to analyze the tendency toward a higher prevalence of genotypes iNOS22*A/A and eNOS*4a4a.
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Affiliation(s)
- Fermín Mearin
- Institute of Functional and Motor Digestive Disorders, Centro Médico Teknon, Barcelona, Spain
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47
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Abstract
Achalasia is a disorder of esophageal motility that has been well documented for over 300 years. Despite this, the initiating factor or factors and the underlying mechanisms leading to the characteristic features of achalasia, the absence of distal esophageal peristalsis and abnormal lower esophageal sphincter relaxation, are still not well understood. Recent work has shed light on changes in neurotransmission and cell signaling in the lower esophagus and lower esophageal sphincter that lead to achalasia. A number of recent reviews have thoroughly discussed diagnostic and therapeutic modalities and the reader is referred to these for in-depth review of these topics. The focus of this review will be on our current understanding of the physiology of esophageal peristalsis and lower esophageal sphincter function as it relates to achalasia and on available evidence for etiology and proposed pathophysiologic mechanisms.
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Affiliation(s)
- R E Kraichely
- Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
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Zarate N, Wang XY, Tougas G, Anvari M, Birch D, Mearin F, Malagelada JR, Huizinga JD. Intramuscular interstitial cells of Cajal associated with mast cells survive nitrergic nerves in achalasia. Neurogastroenterol Motil 2006; 18:556-68. [PMID: 16771771 DOI: 10.1111/j.1365-2982.2006.00788.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Achalasia is dominated by injury to inhibitory nerves. As intramuscular interstitial cells of Cajal (ICC-IM) are proposed to form functional units with nitrergic nerves, their fate in achalasia may be critically important. We studied the relationship between loss of nitrergic nerves and injury to ICC-IM in patients with achalasia and determined associations between ICC-IM and mast cells (MC), using quantitative immunohistochemistry and electron microscopy. Loss of neuronal nitric oxide synthase (nNOS) immunoreactivity was completed within 3 years of acquiring achalasia. Thereafter, progressive ultrastructural injury to remaining nerve structures was evident. Within the first 2 years, the number of ICC-IM did not decline although ultrastructural injury was already present. Thereafter, loss of ICC-IM occurred unrelated to duration of disease. Damage to ICC-IM appeared unrelated to nerve injury. A significant MC infiltration was observed in the musculature; the number of MC was positively related to the persistent number of ICC-IM. Mast cell formed close contacts with ICC-IM and piecemeal-degranulation occurred towards ICC-IM. In conclusion, injury to ICC-IM in achalasia is variable, but not related to duration of disease and injury to nitrergic nerves. MC are prominent and form close functional contact with ICC-IM which may be responsible for their relatively long survival.
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Affiliation(s)
- N Zarate
- IDRP, McMaster University, ON, Canada.
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Latiano A, De Giorgio R, Volta U, Palmieri O, Zagaria C, Stanghellini V, Barbara G, Mangia A, Andriulli A, Corinaldesi R, Annese V. HLA and enteric antineuronal antibodies in patients with achalasia. Neurogastroenterol Motil 2006; 18:520-5. [PMID: 16771767 DOI: 10.1111/j.1365-2982.2006.00772.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The aetiopathogenesis of primary achalasia is largely unknown, although an immunogenetic predisposition is suspected. To establish whether a correlation exists among possible aetiological factors, including class II human leucocyte antigen (HLA) alleles and autoantibodies to enteric neurones, and clinical features of patients with achalasia, a total of 60 patients and 200 healthy subjects were typed by high-resolution HLA-DQ and HLA-DR alleles. Circulating antineuronal antibodies were investigated by using indirect immunofluorescence on enteric neurones of rat ileum and colon and immunoblotting assay in a subset of achalasic patients and in all controls. The DQB1*0502 and DQB1*0601 alleles were significantly increased in patients with achalasia compared with controls (P < 0.03, P < 0.001, respectively). Moreover a negative correlation with the DQB1*0201 allele was found (P = 0.016). As a whole, 14 of 60 (23.3%) achalasia patients were carriers of HLA risk alleles, and 10 of 41 (24.4%) presented antineuronal antibodies. No significant correlation among HLA risk alleles, antineuronal antibodies and clinical features was found. In achalasia, no correlation exists among HLA alleles, antineuronal antibodies and clinical features. However, given the association between achalasia and HLA-DQ1, further research is needed to clarify the role of HLA antigens and antineuronal antibodies in this disease.
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Affiliation(s)
- A Latiano
- U.O. Gastroenterologia, Ospedale CSS-IRCCS, San Giovanni Rotondo, Italy
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Gockel I, Bohl JRE, Doostkam S, Eckardt VF, Junginger T. Spectrum of histopathologic findings in patients with achalasia reflects different etiologies. J Gastroenterol Hepatol 2006; 21:727-33. [PMID: 16677160 DOI: 10.1111/j.1440-1746.2006.04250.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The etiology of achalasia is still unknown. The aim of the present study was to elucidate its underlying pathologies and their chronology by investigation of esophageal specimens in patients undergoing surgery (esophageal resection or myotomy) for achalasia. METHODS In 17 patients with achalasia, histopathologic examinations of the esophageal wall focussing on the myenteric plexus were performed. Preoperative diagnosis was based on clinical evaluation, esophagogastroscopy, barium esophagogram in all, and esophageal manometry in eight patients. The median age at the time of surgery was 54 years (range: 14-78 years). In eight cases, the complete esophageal, body and in nine cases a smooth muscle biopsy including parts of the myenteric plexus from the distal part of the esophagus (high pressure zone) was available. The tissue specimens were fixed in formalin and embedded in paraffin. The staining procedures were hematoxylin and eosin (HE), Elastica van Gieson (EvG), and periodic acid-Schiff (PAS) reaction. Immunohistochemical examinations were performed with antibodies against B and T lymphocytes, neurofilament, protein gene-related product (PGP 9.5), S-100 protein, myosin, desmin, smooth muscle actin and substance P. RESULTS In 13 of 17 patients, a significant reduction of the number of intramural ganglion cells was present. Common findings were a severe fibrosis of the smooth muscle layer (10/17) and obvious myopathic changes of the smooth muscle cells (5/17). Staining for B and T lymphocytes found signs of inflammation in mucosal and muscular areas. Three patients exhibited a marked invasion of eosinophilic granulocytes of the muscularis propria (eosinophilia). Esophageal carcinoma had developed in three patients (squamous cell carcinoma in two and carcinoma in situ in another patient with Barrett's esophagus and high-grade dysplasia). Severe inflammatory reactions (neural, eosinophilic and mucosal) dominated in patients with a longstanding history of achalasia (>10 years) as well as a marked endomysial fibrosis. CONCLUSIONS The histopathological investigations of the esophageal wall in 17 patients undergoing esophageal resection or myotomy for achalasia suggest that the reduction of intramural ganglion cells might be a secondary change, probably due to inflammation triggered by autoimmune mechanisms or a chronic degenerative process of the central and/or peripheral part of the vagal nerve. The primary lesion could also be a severe myopathy of the smooth muscle cells.
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Affiliation(s)
- Ines Gockel
- Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany.
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