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Mittal RK, Gupta A, Fu J, Stark P, Candipali S, Sun L, Nemeh C, Sharma A, Zifan A. Fibrosis in the Hiatus of Esophagus in Patients With Primary Esophageal Motor Disorders: Radiomic Analysis. Neurogastroenterol Motil 2025:e70085. [PMID: 40391471 DOI: 10.1111/nmo.70085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/30/2025] [Accepted: 05/06/2025] [Indexed: 05/21/2025]
Abstract
INTRODUCTION In normal subjects, the esophagus and crus of the diaphragm slide relative to each other during esophageal peristalsis, which is not the case in patients with achalasia esophagus. OBJECTIVE To examine the tissue characteristics of the esophageal hiatus in patients with achalasia esophagus, high amplitude esophageal contractions (HAEC), esophagogastric junction outflow obstruction (EGJOO), and normal subjects using radiomics analysis of the CT images. METHODS A large number of medical records (1221 controls, 409 achalasia, 562 EGJOO, and 349 HAEC) were screened to identify subjects with a CT scan of the abdomen/chest in their record that met the pre-determined criteria. Using multiplanar rotation of CT images, the esophageal hiatus was visualized in a 2D plane. The grayscale intensity distributions (GSID) of the three regions of interest, i.e., (1) subcutaneous adipose tissue, (2) a posterior spine muscle (marker of fibro-connective tissue), and (3) esophageal hiatus were determined. RESULTS No differences in the mean GSID of subcutaneous adipose tissue and muscle were found among the four groups. On the other hand, the esophageal hiatus mean GSID was significantly higher in the three patient groups compared to controls. The GSIDs were higher in achalasia patients than in HAEC and EGJOO patients. The mean GSI of the hiatus was closer to that of the muscle with greater overlap between the hiatus and muscle in the three patient groups; the overlap was greater in achalasia as compared to HAEC and EGJOO patients. CONCLUSION A higher GSI of the hiatus with greater overlap between the hiatus and muscle suggests an increase in fibro-connective tissue in the esophageal hiatus of patients with primary esophageal motility disorders (EMD). We propose that fibrosis in the esophageal hiatus restricts axial separation between the LES and crural diaphragm, which may be important in the pathogenesis of esophageal motor disorders.
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Affiliation(s)
- Ravinder K Mittal
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Anant Gupta
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Jerry Fu
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Paul Stark
- Department of Radiology, San Diego VA Medical Center, San Diego, California, USA
| | - Shreeya Candipali
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Lixin Sun
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Carlos Nemeh
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Arshia Sharma
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
| | - Ali Zifan
- Department of Medicine, Division of Gastroenterology, University of California, San Diego, California, USA
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Wattchow DA, Brookes SJH, Spencer NJ, De Giorgio R, Costa M, Dinning PG. Gut Neuropathies and Intestinal Motility Disorders. Neurogastroenterol Motil 2025:e14995. [PMID: 39777822 DOI: 10.1111/nmo.14995] [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: 04/09/2024] [Revised: 11/26/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND The enteric nervous system plays a key role in the coordination of gastrointestinal motility together with sympathetic, parasympathetic, and extrinsic sensory pathways. In some cases, abnormalities in neural activity in these pathways contribute to disorders of gut motility. Where this is associated with damage or death of enteric neurons, usually detected by microscopy, this is considered a gut neuropathy. PURPOSE This review summarizes recent advances in the identification of neuropathies in a range of gastrointestinal motility disorders.
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Affiliation(s)
- David A Wattchow
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
- Department of Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Simon J H Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Nick J Spencer
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
- Department of Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
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Li XY, Xiang AY, Liu XY, Wang KH, Wang Y, Pan HT, Zhang JY, Yao L, Liu ZQ, Xu JQ, Li XQ, Zhang ZC, Chen WF, Zhou PH, Li QL. Association of circulating cytokine levels and tissue-infiltrating myeloid cells with achalasia: results from Mendelian randomization and validation through clinical characteristics and single-cell RNA sequencing. J Gastroenterol 2024; 59:1079-1091. [PMID: 39377966 DOI: 10.1007/s00535-024-02155-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 09/27/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND Achalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood. METHODS We utilized Mendelian randomization (MR) to explore the causal effects of cytokine levels on achalasia, with cis-expression/protein quantitative trait loci (cis-eQTLs/pQTLs) for 47 cytokines selected from a genome-wide association study (GWAS) meta-analysis and GWAS data for achalasia obtained from FinnGen. For cytokines significantly linked to achalasia, we analyzed their plasma concentrations and expression differences in the lower esophageal sphincter (LES) using enzyme-linked immunosorbent assay and single-cell RNA sequencing (scRNA-seq) profiling, respectively. We further employed bioinformatics approaches to investigate underlying mechanisms. RESULTS We revealed positive associations of circulating Eotaxin, macrophage inflammatory protein-1b (MIP1b), soluble E-selectin (SeSelectin) and TNF-related apoptosis-inducing ligand (TRAIL) with achalasia. When combining MR findings with scRNA-seq data, we observed upregulation of TRAIL (OR = 2.70, 95% CI, 1.20-6.07), encoded by TNFSF10, in monocytes and downregulation of interleukin-1 receptor antagonist (IL-1ra) (OR = 0.70, 95% CI 0.59-0.84), encoded by IL1RN, in FOS_macrophages in achalasia. TNFSF10high monocytes in achalasia displayed activated type I interferon signaling, and IL1RNlow FOS_macrophages exhibited increased intercellular communications with various lymphocytes, together shaping the proinflammatory microenvironment of achalasia. CONCLUSIONS We identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10high monocytes and IL1RNlow macrophages may play a role in the pathogenesis of achalasia.
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Affiliation(s)
- Xin-Yue Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - An-Yi Xiang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Xin-Yang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Ke-Hao Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Yun Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Hai-Ting Pan
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Ji-Yuan Zhang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Lu Yao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Zu-Qiang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Jia-Qi Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Xiao-Qing Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Zhao-Chao Zhang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Wei-Feng Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Ping-Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China.
| | - Quan-Lin Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China.
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Patel J, Kalikar V, Patankar R, Supe A. Is Indocyanine Green the New Gold Standard for Checking Completion of Laparoscopic Heller's Cardiomyotomy? Cureus 2024; 16:e75344. [PMID: 39781145 PMCID: PMC11707402 DOI: 10.7759/cureus.75344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2024] [Indexed: 01/12/2025] Open
Abstract
Achalasia cardia is a primary motility disorder of the esophagus marked by the absence of peristalsis and the failure of the lower esophageal sphincter (LES) to relax during swallowing. The preferred surgical approach is laparoscopic Heller's cardiomyotomy with Dor's fundoplication. Given the significant risks of mucosal perforation and the possibility of incomplete myotomy, which can lead to symptom recurrence, it is essential to ensure both the completeness of the myotomy and the preservation of the mucosal integrity. In this study, we present a case series of 15 patients diagnosed with achalasia cardia who underwent laparoscopic Heller's cardiomyotomy with Dor's fundoplication. Intraoperatively, we utilized intraluminal administration of indocyanine green (ICG) dye as an alternative to endoscopy to assess the completeness of the myotomy and to check for any mucosal perforations.
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Affiliation(s)
- Jainil Patel
- Department of Surgery, Zen Hospital, Mumbai, IND
| | | | | | - Avinash Supe
- Department of Surgery, Zen Hospital, Mumbai, IND
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Savarino EV, Salvador R, Ghisa M, Mari A, Forattini F, Costantini A, De Giorgio R, Zaninotto G. Research gap in esophageal achalasia: a narrative review. Dis Esophagus 2024; 37:doae024. [PMID: 38525929 DOI: 10.1093/dote/doae024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 03/08/2024] [Indexed: 03/26/2024]
Abstract
In recent years, new translational evidence, diagnostic techniques, and innovative therapies have shed new light on esophageal achalasia and revamped the attention on this relatively rare motility disorder. This narrative review aims to highlight the most recent progress and the areas where further research is needed. The four senior authors identified five topics commonly discussed in achalasia management: i.e. pathogenesis, role of functional lumen imaging probe in the diagnostic flow chart of achalasia, how to define the outcome of achalasia treatments, how to manage persistent chest pain after the treatment, and if achalasia patients' may benefit from a regular follow-up. We searched the bibliographic databases to identify systematic reviews, meta-analyses, randomized control trials, and original research articles in English up to December 2023. We provide a summary with the most recent findings in each of the five topics and the critical points where to address future research, such as the immune-genetic patterns of achalasia that might explain the transition among the different phenotypes, the need for a validated clinical definition of treatment success, the use of neuromodulators to manage chest pain, and the need for identifying achalasia patients at risk for cancer and who may benefit of long-term follow-up. Although undoubtedly, progress has been made on the definition and management of achalasia, unmet needs remain. Debated aspects range from mechanistic insights, symptoms, objective measure relationships, and accurate clinical responses to therapeutic interventions. Translational research is eagerly awaited to answer these unresolved questions.
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Affiliation(s)
- Edoardo Vincenzo Savarino
- Gastroenterology Unit, Azienda Ospedale Università of Padua, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Renato Salvador
- Chirurgia Generale 1, Azienda Ospedale Università of Padua, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Matteo Ghisa
- Gastroenterology Unit, Azienda Ospedale Università of Padua, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, The Azrieli Faculty of Medicine, Bar-Ilan University, Tel Aviv, Israel
| | - Francesca Forattini
- Chirurgia Generale 1, Azienda Ospedale Università of Padua, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Andrea Costantini
- Chirurgia Generale 1, Azienda Ospedale Università of Padua, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
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6
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Goyal RK, Rattan S. Role of mechanoregulation in mast cell-mediated immune inflammation of the smooth muscle in the pathophysiology of esophageal motility disorders. Am J Physiol Gastrointest Liver Physiol 2024; 326:G398-G410. [PMID: 38290993 PMCID: PMC11213482 DOI: 10.1152/ajpgi.00258.2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 01/15/2024] [Accepted: 01/29/2024] [Indexed: 02/01/2024]
Abstract
Major esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated with smooth muscle hypertrophy and hypercontractility, whose cause is unknown. This review investigated immune inflammation in the causation of smooth muscle changes in obstructive esophageal bolus transport. Findings suggest that smooth muscle hypertrophy occurs above the obstruction and is due to mechanical stress on the smooth muscles. The mechanostressed smooth muscles release cytokines and other molecules that may recruit and microlocalize mast cells to smooth muscle bundles, so that their products may have a close bidirectional effect on each other. Acting in a paracrine fashion, the inflammatory cytokines induce genetic and epigenetic changes in the smooth muscles, leading to smooth muscle hypercontractility, hypertrophy, and impaired relaxation. These changes may worsen difficulty in the esophageal transport. Immune processes differ in the first phase of obstructive bolus transport, and the second phase of muscle hypertrophy and hypercontractility. Moreover, changes in the type of mechanical stress may change immune response and effect on smooth muscles. Understanding immune signaling in causes of obstructive bolus transport, type of mechanical stress, and associated smooth muscle changes may help pathophysiology-based prevention and targeted treatment of esophageal motility disorders.NEW & NOTEWORTHY Esophageal disorders such as esophageal stricture or achalasia, and diffuse esophageal spasm are associated with smooth muscle hypertrophy and hypercontractility, above the obstruction, yet the cause of such changes is unknown. This review suggests that smooth muscle obstructive disorders may cause mechanical stress on smooth muscle, which then secretes chemicals that recruit, microlocalize, and activate mast cells to initiate immune inflammation, producing functional and structural changes in smooth muscles. Understanding the immune signaling in these changes may help pathophysiology-based prevention and targeted treatment of esophageal motility disorders.
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Affiliation(s)
- Raj K Goyal
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts, United States
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts, United States
| | - Satish Rattan
- Department of Medicine, Division of Gastroenterology and Hepatology, Sidney Kummel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, United States
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Becker CB, Jensen HE. Clinicopathologic evaluation of congenital idiopathic megaesophagus in a Gordon Setter puppy: a case report and development and application of peripherin immunohistochemistry for detection of ganglion cells. J Vet Diagn Invest 2024; 36:254-257. [PMID: 38305240 PMCID: PMC10929633 DOI: 10.1177/10406387241226950] [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: 02/03/2024] Open
Abstract
We examined a case of congenital idiopathic megaesophagus (CIM) in a 5-wk-old female Gordon Setter puppy by means of contrast radiography, autopsy, histopathology, and immunohistochemistry. Clinical and radiologic findings included weight stagnation and marked generalized esophageal dilation with ventral displacement of the heart and lungs. These findings were confirmed at autopsy, and segments of the thoracic esophagus were sampled for histopathology. On histopathology, diffuse esophageal muscular atrophy, mucosal erosions, mononuclear inflammation, and a marked reduction in the number of myenteric plexus structures and number of ganglion cells were present (aganglionosis). The latter was determined immunohistochemically using an anti-peripherin antibody as the primary reagent, which provides a strong tool for the histologic confirmation of CIM. The histologic findings share some similarities to lesions associated with megaesophagus in Friesian foals, as well as esophageal achalasia and Hirschsprung disease in humans.
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Affiliation(s)
- Cecilie B. Becker
- Section for Special Pathology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Henrik E. Jensen
- Section for Special Pathology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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8
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Chuah KH, Ramasami N, Mahendran HA, Shanmuganathan G, Koleth GG, Voon K, Gew LT, Jahit MS, Lau PC, Muthukaruppan R, Said RHM, Mahadeva S, Ho SH, Lim SY, Tee SC, Siow SL, Ooi WK, Lee YY. Malaysian joint societies' consensus recommendations on diagnosis and management of disorders of esophagogastric junction outflow. J Gastroenterol Hepatol 2024; 39:431-445. [PMID: 38087846 DOI: 10.1111/jgh.16403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 09/13/2023] [Accepted: 10/18/2023] [Indexed: 03/05/2024]
Abstract
Disorders of esophagogastric junction (EGJ) outflow, including achalasia and EGJ outflow obstruction, are motility disorders characterized by inadequate relaxation of lower esophageal sphincter with or without impaired esophageal peristalsis. Current guidelines are technical and less practical in the Asia-Pacific region, and there are still massive challenges in timely diagnosis and managing these disorders effectively. Therefore, a Malaysian joint societies' task force has developed a consensus on disorders of EGJ outflow based on the latest evidence, while taking into consideration the practical relevance of local and regional context and resources. Twenty-one statements were established after a series of meetings and extensive review of literatures. The Delphi method was used in the consensus voting process. This consensus focuses on the definition, diagnostic investigations, the aims of treatment outcome, non-surgical or surgical treatment options, management of treatment failure or relapse, and the management of complications. This consensus advocates the use of high-resolution esophageal manometry for diagnosis of disorders of EGJ outflow. Myotomy, via either endoscopy or laparoscopy, is the preferred treatment option, while pneumatic dilatation can serve as a secondary option. Evaluation and management of complications including post-procedural reflux and cancer surveillance are recommended.
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Affiliation(s)
- Kee Huat Chuah
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Naveen Ramasami
- Gastroenterology and Hepatology Unit, Department of Medicine, Sultanah Bahiyah Hospital, Alor Setar, Kedah, Malaysia
| | | | | | - Glenn George Koleth
- Gastroenterology and Hepatology Unit, Department of Medicine, Sultan Ismail Hospital, Johor Bahru, Johor, Malaysia
| | - Kelvin Voon
- Department of General Surgery, Penang General Hospital, George Town, Penang, Malaysia
| | - Lai Teck Gew
- Gastroenterology and Hepatology Unit, Department of Medicine, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia
| | | | - Peng Choong Lau
- Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
- Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Raman Muthukaruppan
- Gastroenterology and Hepatology Unit, Department of Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
| | - Rosaida Hj Md Said
- Gastroenterology and Hepatology Unit, Department of Medicine, Serdang Hospital, Serdang, Selangor, Malaysia
| | - Sanjiv Mahadeva
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Shiaw-Hooi Ho
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Shyang Yee Lim
- Department of General Surgery, Penang General Hospital, George Town, Penang, Malaysia
| | - Sze Chee Tee
- Department of Surgery, National Cancer Institute, Putrajaya, Malaysia
| | - Sze Li Siow
- Department of General Surgery, Sarawak General Hospital, Kuching, Sarawak, Malaysia
| | - Wei Keat Ooi
- Department of Surgery, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia
- GI Function and Motility Unit, Universiti Sains Malaysia Hospital, Kota Bharu, Kelantan, Malaysia
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9
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Dervin H, Endersby J, Sanagapalli S, Mills H, Sweis R. Assessing the diagnostic yield of achalasia using provocative testing in high-resolution esophageal manometry: Serial diagnostic study. Neurogastroenterol Motil 2023; 35:e14668. [PMID: 37846024 DOI: 10.1111/nmo.14668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 07/27/2023] [Accepted: 08/19/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND Chicago Classification v4.0 recommends that if achalasia is demonstrated with single water swallows (SWS); provocative testing is not required. We determine whether provocative testing in patients with suspected achalasia can change manometric findings and reproduce symptoms. METHODS Between 2016 and 2022, 127 consecutive manometry studies of patients with achalasia were retrospectively analyzed. All patients underwent SWS, a solid meal (SM) and/or a rapid drink challenge (RDC). Demographic data, fluoroscopy, gastroscopy, and pre-and post-treatment Eckardt scores were collated. KEY RESULTS Of 127 achalasia patients (50.6 ± 16.6 years and 54.6% male), all completed a SM and 116 (91.3%) completed RDC; overall 83 were naïve (65.4%) to previous therapy. 15.4% patients with normal integrated relaxation pressure (IRP) on SWS demonstrated obstruction with RDC. SM gave a different achalasia phenotype in 44.9% of patients (p ⟨ 0.001). Twelve patients with normal IRP during SWS had persistent/recurrent obstruction during provocative testing; 83.3% had previous achalasia therapy. None of 13 patients with Type III (TIII) achalasia with SWS exhibited a change in manometric findings with provocative testing. Impedance bolus heights were lower in patients with TIII achalasia and those with normal IRP with SWS. During the SM, symptoms were reproduced in 56.7% of patients. Forty-six of 103 patients (44.7%) underwent therapy based upon the final achalasia subtype which was defined by the provocative test result of the high-resolution manometry (HRM) study. All treatments were effective, regardless of the achalasia subtype. CONCLUSIONS AND INFERENCES Manometric findings remain unchanged when TIII achalasia is diagnosed with SWS. In patients with normal IRP, Type I, or Type II achalasia during SWS, provocative testing can alter achalasia phenotype or uncover achalasia where diagnosis is unclear. Further, it can reproduce symptoms. Such findings can personalize and guide effective therapeutic decisions.
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Affiliation(s)
- Humayra Dervin
- GI Physiology Unit, University College London, London, UK
| | - James Endersby
- GI Physiology Unit, University College London, London, UK
| | - Santosh Sanagapalli
- GI Physiology Unit, University College London, London, UK
- St Vincent's Hospital, Sydney, Victoria, Australia
| | - Holly Mills
- GI Physiology Unit, University College London, London, UK
| | - Rami Sweis
- GI Physiology Unit, University College London, London, UK
- University College London, London, UK
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10
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Yip JLK, Xavier S, Balasuriya GK, Hill-Yardin EL, Spencer SJ. Macrophage regulation of the "second brain": CD163 intestinal macrophages interact with inhibitory interneurons to regulate colonic motility - evidence from the Cx3cr1-Dtr rat model. Front Immunol 2023; 14:1269890. [PMID: 37868978 PMCID: PMC10585175 DOI: 10.3389/fimmu.2023.1269890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 09/22/2023] [Indexed: 10/24/2023] Open
Abstract
Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on gastrointestinal motility through interaction with myenteric neurons that contribute to the gut-brain axis, but this mechanism is yet to be properly characterised. The CX3CR1 chemokine receptor is expressed in the majority of intestinal macrophages, so we used a conditional knockout Cx3cr1-Dtr (diphtheria toxin receptor) rat model to transiently ablate these cells. We then utilized ex vivo video imaging to evaluate colonic motility. Our previous studies in brain suggested that Cx3cr1-expressing cells repopulate by 7 days after depletion in this model, so we performed our experiments at both the 48 hr (macrophage depletion) and 7-day (macrophage repopulation) time points. We also investigated whether inhibitory neuronal input driven by nitric oxide from the enteric nervous system is required for the regulation of colonic motility by intestinal macrophages. Our results demonstrated that CD163-positive resident intestinal macrophages are important in regulating colonic motility in the absence of this major inhibitory neuronal input. In addition, we show that intestinal macrophages are indispensable in maintaining a healthy intestinal structure. Our study provides a novel understanding of the interplay between the enteric nervous system and intestinal macrophages in colonic motility. We highlight intestinal macrophages as a potential therapeutic target for gastrointestinal motility disorders when inhibitory neuronal input is suppressed.
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Affiliation(s)
- Jackson L. K. Yip
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
| | - Soniya Xavier
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
| | - Gayathri K. Balasuriya
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
- Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan
| | - Elisa L. Hill-Yardin
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
| | - Sarah J. Spencer
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
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11
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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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12
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Liu ZQ, Dai H, Yao L, Chen WF, Wang Y, Ma LY, Li XQ, Lin SL, He MJ, Gao PT, Liu XY, Xu JX, Xu XY, Wang KH, Wang L, Chen L, Zhou PH, Li QL. A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia. Nat Commun 2023; 14:4685. [PMID: 37542039 PMCID: PMC10403544 DOI: 10.1038/s41467-023-39750-5] [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: 06/22/2022] [Accepted: 06/28/2023] [Indexed: 08/06/2023] Open
Abstract
Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.
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Affiliation(s)
- Zu-Qiang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Hao Dai
- Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
| | - Lu Yao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Wei-Feng Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Yun Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Li-Yun Ma
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Xiao-Qing Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Sheng-Li Lin
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Meng-Jiang He
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Ping-Ting Gao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Xin-Yang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Jia-Xin Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Xiao-Yue Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Ke-Hao Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Li Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China
| | - Luonan Chen
- Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
- Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
| | - Ping-Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China.
| | - Quan-Lin Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
- Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China.
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13
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Deguchi K, Zambaiti E, De Coppi P. Regenerative medicine: current research and perspective in pediatric surgery. Pediatr Surg Int 2023; 39:167. [PMID: 37014468 PMCID: PMC10073065 DOI: 10.1007/s00383-023-05438-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/01/2023] [Indexed: 04/05/2023]
Abstract
The field of regenerative medicine, encompassing several disciplines including stem cell biology and tissue engineering, continues to advance with the accumulating research on cell manipulation technologies, gene therapy and new materials. Recent progress in preclinical and clinical studies may transcend the boundaries of regenerative medicine from laboratory research towards clinical reality. However, for the ultimate goal to construct bioengineered transplantable organs, a number of issues still need to be addressed. In particular, engineering of elaborate tissues and organs requires a fine combination of different relevant aspects; not only the repopulation of multiple cell phenotypes in an appropriate distribution but also the adjustment of the host environmental factors such as vascularisation, innervation and immunomodulation. The aim of this review article is to provide an overview of the recent discoveries and development in stem cells and tissue engineering, which are inseparably interconnected. The current status of research on tissue stem cells and bioengineering, and the possibilities for application in specific organs relevant to paediatric surgery have been specifically focused and outlined.
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Affiliation(s)
- Koichi Deguchi
- Stem Cells and Regenerative Medicine Section, University College London Great Ormond Street Institute of Child Health, London, UK
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Elisa Zambaiti
- Stem Cells and Regenerative Medicine Section, University College London Great Ormond Street Institute of Child Health, London, UK
- UOC Chirurgia Pediatrica, Ospedale Infantile Regina Margherita, Turin, Italy
| | - Paolo De Coppi
- Stem Cells and Regenerative Medicine Section, University College London Great Ormond Street Institute of Child Health, London, UK.
- NIHR BRC SNAPS Great Ormond Street Hospitals, London, UK.
- Stem Cells and Regenerative Medicine Section, Faculty of Population Health Sciences, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
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14
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Hata Y, Sato H, Shimamura Y, Abe H, Shiwaku A, Shiota J, Sato C, Ominami M, Fukuda H, Ogawa R, Nakamura J, Tatsuta T, Ikebuchi Y, Yokomichi H, Ihara E, Inoue H. Impact of peroral endoscopic myotomy on high-resolution manometry findings and their association with the procedure's outcomes. Gastrointest Endosc 2023; 97:673-683.e2. [PMID: 36328208 DOI: 10.1016/j.gie.2022.10.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 10/15/2022] [Accepted: 10/20/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. METHODS In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. RESULTS Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR, .22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR, .42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. CONCLUSIONS Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.
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Affiliation(s)
- Yoshitaka Hata
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroki Sato
- Division of Gastroenterology & Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Yuto Shimamura
- Digestive Diseases Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
| | - Hirofumi Abe
- Department of Gastroenterology, Kobe University Hospital, Kobe, Japan
| | - Akio Shiwaku
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Junya Shiota
- Department of Gastroenterology & Hepatology, Nagasaki University Hospital, Nagasaki, Japan
| | - Chiaki Sato
- Division of Advanced Surgical Science and Technology, Tohoku University School of Medicine, Sendai, Japan
| | - Masaki Ominami
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Fukuda
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Ryo Ogawa
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Jun Nakamura
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Tetsuya Tatsuta
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Aomori, Japan
| | - Yuichiro Ikebuchi
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Hiroshi Yokomichi
- Department of Health Sciences, University of Yamanashi, Yamanashi, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Haruhiro Inoue
- Digestive Diseases Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
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15
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Kahrilas PJ, Carlson DA, Pandolfino JE. Advances in the Diagnosis and Management of Achalasia and Achalasia-Like Syndromes: Insights From HRM and FLIP. GASTRO HEP ADVANCES 2023; 2:701-710. [PMID: 37503535 PMCID: PMC10373628 DOI: 10.1016/j.gastha.2023.02.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
High-resolution manometry, Chicago Classification v4.0, the functional lumen imaging probe, Panometry, and peroral endoscopic myotomy (POEM) are all now integral parts of the landscape for managing achalasia or, more precisely, achalasia-like syndromes. This narrative review examines the impact of these innovations on the management of achalasia-like syndromes. High-resolution manometry was the disruptive technology that prompted the paradigm shift to thinking of motility disorders as patterns of obstructive physiology involving the esophagogastric junction and/or the distal esophagus rather than as siloed entities. An early observation was that the cardinal feature of achalasia-impaired lower esophageal sphincter relaxation-can occur in several subtypes: without peristalsis, with pan-esophageal pressurization, with premature (spastic) distal esophageal contractions, or even with preserved peristalsis (esophagogastric junction outlet obstruction). Furthermore, there being no biomarker for achalasia, no manometric pattern is perfectly sensitive or specific for 'achalasia' and there is also no 'gold standard' for the diagnosis. Consequently, complimentary physiological testing with a timed barium esophagram or functional lumen imaging probe are employed both to improve the detection of patients likely to respond to treatments for 'achalasia' and to characterize other syndromes also likely to benefit from achalasia therapies. These findings have become particularly relevant with the development of a minimally invasive technique for performing a tailored esophageal myotomy, POEM. Now and in the future, optimal achalasia management is to render treatment in a phenotype-specific manner, that is, POEM calibrated in a patient-specific manner for obstructive physiology including the distal esophagus and more conservative strategies such as a short POEM or pneumatic dilation for obstructive physiology limited to the lower esophageal sphincter.
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Affiliation(s)
- Peter J Kahrilas
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Dustin A Carlson
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - John E Pandolfino
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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16
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Rolland S, Paterson W, Bechara R. Achalasia: Current therapeutic options. Neurogastroenterol Motil 2023; 35:e14459. [PMID: 36153803 DOI: 10.1111/nmo.14459] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 07/13/2022] [Accepted: 08/01/2022] [Indexed: 12/31/2022]
Abstract
Achalasia is an esophageal motor disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and absent peristalsis in the smooth muscle esophageal body. As a result, patients typically experience dysphagia, regurgitation, chest pain, and weight loss. Over the past 10-15 years, there has been a resurgence of interest in the evaluation of therapies for achalasia. Unfortunately, little progress in the development of effective pharmacological treatments has been made. Botulinum toxin injection provides some relief of symptoms in many patients but requires periodic reinjection that may provide progressively less benefit over time. There are now three well-established, safe, and effective therapies for the treatment of achalasia: pneumatic dilation (PD), laparoscopic Heller myotomy (LHM), and peroral endoscopic myotomy (POEM) which can lead to marked symptom improvement in most patients. Each treatment has a specific constellation of risks, benefits, and recurrence rate. The first-line treatment used will depend on patient preference, achalasia subtype, and local expertise. The recent impressive advances in both the art and science of achalasia therapy are explored with a comprehensive review of the various treatment modalities and comparative controlled clinical trials. In addition, key technical pearls of the procedural treatments are demonstrated.
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Affiliation(s)
- Sebastien Rolland
- Division of Gastroenterology, Hôpital Maisonneuve-Rosemont and Université de Montreal, Montreal, Quebec, Canada
| | - William Paterson
- Division of Gastroenterology and GI Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Robert Bechara
- Division of Gastroenterology and GI Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
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17
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Zhao W, Wang B, Zhang L, Jin H. Eosinophils Infiltration in Esophageal Muscularis Propria Induces Achalasia-like Esophageal Motility Disorder in Mice. Biomolecules 2022; 12:biom12121865. [PMID: 36551293 PMCID: PMC9775547 DOI: 10.3390/biom12121865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 12/08/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Eosinophil infiltration in esophageal muscularis propria is common in achalasia (AC). This study aims to evaluate the effect of eosinophil infiltration in muscularis propria of the esophagus on esophageal motility in mice. A mouse model with eosinophil infiltration in the esophageal muscle layer was established by long term Ovalbumin (OVA) exposure. The histopathology features of esophageal muscularis propria as well as parameters of esophageal motility, such as lower esophageal sphincter pressure (LESP) and esophageal emptying, were compared between model and control group. In addition, the histopathology and motility of esophagus at each time point in the model group were compared. The esophageal motor function severely deteriorated in the model group, mimicking the abnormal esophageal motility of AC, with more eosinophils and fewer SOX-10-IR cells in esophageal muscularis propria in the model group, compared with control. With the prolongation of OVA treatment, esophageal motility disorder was aggravated, accompanied by increased eosinophils in the the muscle layer of esophagus and decreased SOX-10-IR cells in the model group. In addition, the eosinophil count was negatively correlated with SOX-10-IR cells. Long-term exposure to OVA assisted by alum may induce eosinophil infiltration in esophageal muscularis propria, reduced SOX-10-IR cells and abnormal esophageal motility, which simulates the functional and histopathological features of some AC patients. This suggests that eosinophil infiltration in esophageal muscularis propria may play a role in the pathogenesis of a subgroup of AC.
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Affiliation(s)
| | | | - Lili Zhang
- Correspondence: (L.Z.); (H.J.); Tel./Fax: +86-2260362608 (H.J.)
| | - Hong Jin
- Correspondence: (L.Z.); (H.J.); Tel./Fax: +86-2260362608 (H.J.)
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18
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Abstract
BACKGROUND Laparoscopic Heller's cardiomyotomy (LHC) is the preferred treatment of achalasia. It improves dysphagia by dividing muscles of the lower oesophageal sphincter, but this intervention can result in debilitating gastro-oesophageal reflux symptoms in some patients. To prevent these reflux symptoms, most surgeons add a fundoplication to Heller's cardiomyotomy, but there is no consensus regarding this or the type of fundoplication which is best suited for the purpose. OBJECTIVES To assess how the addition of a fundoplication affects postoperative reflux and dysphagia in people undergoing LHC and compare the different types of fundoplications used in combination with LHC to determine which is better at controlling reflux without worsening the dysphagia. SEARCH METHODS We searched three databases (CENTRAL, MEDLINE and Embase) on 31 October 2021 and trial registers to identify all published and unpublished randomised controlled trials (RCTs) in any language, comparing different fundoplications used in combination with LHC to treat achalasia. We also included RCTs where LHC with a fundoplication is compared with LHC without any fundoplication. SELECTION CRITERIA We only included RCTs which recruited adult participants with achalasia undergoing LHC with minimal hiatal dissection. We excluded non-randomised studies or studies involving paediatric participants. We also excluded studies where the procedure was done by open surgery and where circumferential hiatal dissection of the oesophagus was carried out, unless it was necessary to reduce a hiatus hernia or to facilitate a Toupet or Nissen fundoplication. DATA COLLECTION AND ANALYSIS Two review authors independently identified studies to be included, assessed risk of bias using the Cochrane RoB 1 tool, and extracted the data. We calculated the risk ratio (RR) with 95% confidence interval (CI) using both fixed-effect and random-effect models with Review Manager (RevMan) software. MAIN RESULTS We included eight studies in this review, with a total of 571 participants with an average age of 45 years (range 33.5 to 50). LHC without any fundoplication was performed in 65 (11.3%) participants, 298 (52.1%) had Dor fundoplication, 81 (14.1%) had Toupet fundoplication, 72 (12.6%) had Nissen's fundoplication, and 55 (9.6%) participants had angle of His accentuation. Three studies with a total of 143 participants compared LHC + Dor to LHC without fundoplication. We found that the evidence is very uncertain as to whether the addition of a Dor fundoplication made any difference to the outcome of postoperative pathological acid reflux (RR 0.37, 95% CI 0.07 to 1.89; I2 = 56%; 2 studies, 97 participants; very low-certainty evidence) and uncertain for severe postoperative dysphagia (RR 3.00, 95% CI 0.34 to 26.33; I2 = 0%; 3 studies, 142 participants; low-certainty evidence). Three studies with 174 participants compared LHC + Dor to LHC + Toupet. The evidence suggests that there may be little to no difference in the outcomes of postoperative pathological acid reflux (RR 0.75, 95% CI 0.23 to 2.43; I2 = 60%; 3 studies, 105 participants; low-certainty evidence) and severe postoperative dysphagia (RR 0.78, 95% CI 0.19 to 3.15; I2 = 0%; 3 studies, 123 participants; low-certainty evidence) between the two interventions, but the certainty of the evidence is low. One study with 138 participants compared LHC + Dor to LHC + Nissen. Nissen fundoplication caused increased severe postoperative dysphagia (RR 0.19, 95% CI 0.04 to 0.83; 1 study, 138 participants; high-certainty evidence) when compared to Dor fundoplication. This study did not show a difference in postoperative pathological acid reflux (RR 4.72, 95% CI 0.23 to 96.59; 1 study, 138 participants; low-certainty evidence), but the certainty of evidence is low. One study with 110 participants compared LHC + Dor with LCH + angle of His accentuation, and reported that severe postoperative dysphagia was similar between the two interventions (RR 1.56, 95% CI 0.27 to 8.95; 1 study, 110 participants; moderate-certainty evidence), with moderate certainty of evidence. This study did not report on postoperative pathological acid reflux. AUTHORS' CONCLUSIONS When LHC was performed with minimal hiatal dissection, we were very uncertain whether the addition of a Dor fundoplication made a difference in controlling postoperative reflux, and we were uncertain if it increased the risk of severe postoperative dysphagia. There may be little to no difference in the outcomes of postoperative pathological acid reflux or severe dysphagia between Dor and Toupet fundoplications when used in combination with LHC, but the certainty of the evidence is low. Nissen (total) fundoplication used in combination with LHC for achalasia increased the risk of severe postoperative dysphagia. The angle of His accentuation and Dor fundoplication had a similar effect on severe postoperative dysphagia when combined with LHC, but their effect on postoperative pathological acid reflux was not reported.
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Affiliation(s)
- Sumit Midya
- Department of General Surgery, Frimley Park Hospital, Frimley, UK
| | - Debasish Ghosh
- Department of General Surgery, Royal Berkshire Hospital, Reading, UK
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19
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Jain AS, Allamneni C, Kline M, Dalsania R, Godiers M, Keilin S, Srinivasan S, Mittal R. Relationship between dysphagia, lower esophageal sphincter relaxation, and esophagogastric junction distensibility. Neurogastroenterol Motil 2022; 34:e14319. [PMID: 35060256 DOI: 10.1111/nmo.14319] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/30/2021] [Accepted: 01/05/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND It is debated whether high-resolution manometric (HRM) integrated relaxation pressure (IRP) or functional lumen imaging probe (FLIP) distensibility index (DI) is the superior measure of esophagogastric junction (EGJ) opening. We examined the relationship between the DI and IRP and assessed correlations with dysphagia symptoms in patients with achalasia and EGJ outflow obstruction (EGJOO). METHODS Patients with achalasia and those with barium tablet retention at the EGJ were grouped as follows: Group 1:Achalasia (IRP ≥ 15 mmHg + complete absence of normal peristalsis); Group 2: Manometric +FLIP EGJOO (IRP ≥ 15 mmHg with some intact peristalsis + DI ≤ 2.8 mm2 /mmHg); Group 3: Abnormal DI only (DI ≤ 2.8 mm2 /mmHg + IRP <15 mmHg); and Group 4: Normal IRP and DI (IRP ≥ 15 mmHg + DI > 2.8 mm2 /mmHg). Correlation between the DI, baseline lower esophageal sphincter pressure (BLESP), IRP, and dysphagia (Eckardt score) was assessed. Multivariable analysis was used to assess variables associated with dysphagia score ≥2. KEY RESULTS A total of 79 patients were included: Group 1 (n = 31), Group 2 (n = 33), Group 3 (n = 14), and Group 4 (n = 1). DI did not correlate with BLESP or IRP in the whole sample or subgroups. DI was the only variable associated with dysphagia score ≥2 (p = 0.006). DI < 1.25 mm2 /mmHg had sensitivity of 87% and specificity of 52% (p = 0.0003) for dysphagia score ≥2. CONCLUSIONS & INFERENCES DI does not correlate with HRM EGJ measurements and is the metric with the strongest effect on dysphagia severity. The various biological elements that may cause restrictive EGJ function should be the subject of future studies.
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Affiliation(s)
- Anand S Jain
- Division of Digestive Diseases, Emory University Department of Medicine, Atlanta, Georgia, USA
| | - Chaitanya Allamneni
- Division of Digestive Diseases, Emory University Department of Medicine, Atlanta, Georgia, USA
| | - Meredith Kline
- Emory University School of Medicine, Atlanta, Georgia, USA
| | - Raj Dalsania
- Division of Digestive Diseases, Emory University Department of Medicine, Atlanta, Georgia, USA
| | - Marie Godiers
- Division of Digestive Diseases, Emory University Department of Medicine, Atlanta, Georgia, USA
| | - Steven Keilin
- Division of Digestive Diseases, Emory University Department of Medicine, Atlanta, Georgia, USA
| | - Shanthi Srinivasan
- Division of Digestive Diseases, Emory University Department of Medicine, Atlanta, Georgia, USA
| | - Ravinder Mittal
- Division of Gastroenterology and Digestive Diseases, University of California-San Diego Department of Medicine, San Diego, California, USA
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20
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Effect of esophageal muscle fibrosis on prognosis of per-oral endoscopic myotomy (POEM) in achalasia patients. Surg Endosc 2022; 36:7477-7485. [PMID: 35534736 DOI: 10.1007/s00464-022-09172-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 02/21/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND AND AIMS Although esophageal smooth muscle fibrosis of achalasia (AC) patients has been described, the role and mechanism remain unclear. The aim of this study was to evaluate the fibrosis in the distal esophageal muscle in patients with AC and explore its relationship with prognosis of per-oral endoscopic myotomy (POEM). METHODS Lower esophageal sphincter (LES) muscle from forty patients undergoing POEM for AC were obtained at the time of surgery. Control specimens consisted of similar muscle taken from distal esophagectomy for gastric tumors. The muscle fibrosis were assessed by Masson staining and confirmed by immunohistochemistry for collagen I and III. The total number of eosinophil within the myenteric propria were counted. In addition, clinical data were obtained through electronic medical records. Statistical comparison between groups were made. RESULTS A significantly higher proportion of fibrosis in AC as compared with controls (P = 0.000). Eosinophil count, TGF-β1, collagen I, and III were higher than those of control (P = 0.000, P = 0.001, P = 0.011, and P = 0.002, respectively). TGF-β1, collagen I, and III were positively correlated with eosinophil count (all P < 0.05). Furthermore, the proportion of severe LES fibrosis in patients who failed to respond to POEM two years after operation was higher than that in responders (P = 0.028). And, Eckardt score two years after POEM was also positively correlated with degree of fibrosis-related cytokines (all P < 0.05). CONCLUSION Smooth muscle fibrosis was prominent in lower part of esophagus of AC and positively correlated with severity of symptoms two years after POEM. The fibrosis might be relevant to eosinophil infiltration and TGF-β1. Further studies are required to more clearly delineate the mechanism of muscle fibrosis and its correlation with prognosis of therapy for this idiopathic disease.
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21
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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: 60] [Impact Index Per Article: 20.0] [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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22
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Hakimi T, Karimi R. Childhood esophageal achalasia: Case report from Afghanistan with literature review. Int J Surg Case Rep 2022; 94:107112. [PMID: 35658288 PMCID: PMC9118120 DOI: 10.1016/j.ijscr.2022.107112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/17/2022] [Accepted: 04/17/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction and importance Esophageal achalasia is a motility disorder of the esophagus with unknown etiology characterized by the failure of lower esophageal sphincter relaxation. Diagnosis is made by barium esophagography, endoscopy, and esophageal manometery. Heller Esophagomyotomy along with Dor's fundoplication is the treatment of choice. Persisting undiagnosed cases may lead to malnutrition. Case presentation We present a case of an 8-year-old child suffering from dysphagia and regurgitation. The child was misdiagnosed and maltreated for the suspicion of respiratory tract and gastrointestinal problems in the local clinics. During this time, he remained unresponsive to the mentioned treatments, and the local physician advised him to have an upper gastrointestinal (GI) endoscopy, which revealed esophageal achalasia (EA). On admission to our pediatric surgery ward, the patient had coexistent parotitis, which was treated conservatively. Following recovery, the patient was prepared for surgery and underwent esophageal myotomy along with Dor's fundoplication. Clinical discussion Esophageal achalasia is rare in children, but poses major health challenges to children if left untreated. Symptomatic treatment may mask the actual picture of the problem and last for years. Following surgery and discharge from the hospital in a three-month follow-up interval of time, our patient exhibited full recovery, with gaining 4 kg weight. Conclusions Respiratory and gastrointestinal conditions with similar signs and symptoms should always be considered in differential diagnosis of esophageal achalasia, especially where there is no direct access to a pediatric specialized complex. On-time evaluation and treatment will further prevent children from malnutrition in long-lasting undiagnosed patients.
Esophageal achalasia is a motility disorder with unknown etiology. Esophageal achalasia is rare in children. Dysphagia and respiratory infection will mask the actual picture of the problem. Unprofessional symptomatic treatment for a long time is the main cause of undiagnosed patient and may lead to malnutrition.
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Affiliation(s)
- Turyalai Hakimi
- Department of Pediatric Surgery, Kabul University of medical science, Maiwand teaching hospital, Kabul, Afghanistan.
| | - Ramazan Karimi
- Department of Pediatric Surgery, Kabul University of medical science, Maiwand teaching hospital, Kabul, Afghanistan
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Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy. Dig Dis Sci 2022; 67:170-176. [PMID: 33502676 PMCID: PMC7838844 DOI: 10.1007/s10620-021-06827-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 01/06/2021] [Indexed: 01/17/2023]
Abstract
BACKGROUND The relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia. PATIENTS AND METHODS All enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined. KEY RESULTS Twenty consecutive patients (65% female, age range: 21-84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy. CONCLUSIONS AND INFERENCES Submucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.
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24
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Liu X, Kuo E, Wang K, Perbtani YB, Yang D, Draganov P. Histologic Findings in Mucosa and Muscularis Propria Biopsied During Peroral Endoscopic Myotomy in Patients With Achalasia. Gastroenterology Res 2021; 14:281-289. [PMID: 34804272 PMCID: PMC8577593 DOI: 10.14740/gr1454] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 08/24/2021] [Indexed: 11/11/2022] Open
Abstract
Background Peroral endoscopic myotomy (POEM) has been increasingly used to treat achalasia. Previous studies have reported high frequency of muscular eosinophilic infiltration in achalasia. Esophageal mucosal changes in achalasia have only been studied in esophagectomy specimens. Cardia mucosal changes in achalasia have not been reported previously. We aimed to further characterize the esophageal, gastric cardia, and muscularis propria changes in achalasia. Methods This was a pilot study. Patients with clinically and radiographically confirmed achalasia who underwent POEM were enrolled in the study. Mucosal biopsies were taken 1 cm proximal and 1 cm distal to the gastroesophageal junction, and muscularis propria biopsies were taken from the mid esophagus. Tissues were submitted for histological evaluation. Results Eighteen patients (10 male and eight female, mean age: 60.7 (standard deviation (SD): 13) years) were enrolled in this pilot study. Nine patients had type II achalasia, two type III, one type I, five esophageal gastric outlet obstruction, and one unspecific type achalasia. The mean duration of symptoms prior to POEM was 79 (range 1 - 480) months. All patients had a dilated esophagus on examination, but no endoscopic evidence of Barrett's esophagus. Esophageal, gastric cardia, and muscular biopsies were performed in 17, 13, and 17 patients, respectively. Basal hyperplasia, spongiosis, ballooning, and parakeratosis were seen in 92.3%, 100%, 100%, and 76.5% of cases, respectively. Intraepithelial lymphocytosis was seen in 70.5% of cases, and active esophagitis was seen in 23.5% of case. Six (35.3%) cases had few intraepithelial eosinophils, but none of them had > 15 eosinophils per high power field. Histologic findings in gastric cardia mucosa included carditis (69.2%), H. pylori gastritis (7.6%), and reactive gastropathy (15.4%). One case (7.6%) showed low-grade dysplasia arising from intestinal metaplasia in the cardia. Absence of ganglion cells in the muscular biopsies was noted in 88.2% of cases, and the remaining two showed rare residual ganglion cells with ganglionitis in one case (5.8%). Muscular atrophy and interstitial fibrosis were observed in 52.9% and 82.3% of the cases, respectively. Two cases (11.7%) had eosinophilic inflammation in the muscularis propria and one of them was accompanied by lymphocytic inflammation. Conclusions Muscular biopsies in our study revealed loss of ganglion cells, supporting the view that achalasia is a primary esophageal disease with ganglion cell depletion. Squamous mucosa in achalasia showed changes mimicking reflux and lymphocytic esophagitis. Cardia mucosa in achalasia patients often were inflamed and uncommonly showed intestinal metaplasia and glandular dysplasia.
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Affiliation(s)
- Xiuli Liu
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
| | - Enoch Kuo
- Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Kai Wang
- Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Yassen B Perbtani
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Dennis Yang
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Peter Draganov
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
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25
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Goto O, Higuchi K, Tatsuguchi A, Koizumi E, Noda H, Onda T, Omori J, Kaise M, Iwakiri K. Novel Method of Sampling the Gastrointestinal Muscle Layer: Feasibility of Endoscopic Muscular Resection with a Ligation Device in an in Vivo Porcine Model. J NIPPON MED SCH 2021; 88:441-447. [PMID: 34789604 DOI: 10.1272/jnms.jnms.2021_88-602] [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]
Abstract
BACKGROUND Gastrointestinal muscular sampling is useful in the histological assessment of functional gastrointestinal disorders. We devised a new sampling method to obtain a large volume of muscle tissues and then investigated the feasibility and safety of endoscopic muscular resection with a ligation device in an in vivo porcine model. METHODS After establishing a submucosal tunnel, a rubber band was placed on the muscle tissue by sucking the exposed muscle layer. Thereafter, the established pseudopolyp was removed using an electrocautery snare, and the entry site of the submucosal tunnel was closed endoscopically. This procedure was performed at three sites in the esophagus and stomach of two pigs. The technical success, histology, and survival rate on postoperative day 7 were examined postoperatively. RESULTS We successfully completed the mentioned procedure in 11 of the 12 sites (92%), without the occurrence of severe adverse events. The median diameters of obtained tissues from the esophagus and stomach, respectively, were 5 mm and 10 mm. Histologically, both the inner and outer muscle layers were included in all specimens. The postprocedural course was found uneventful in both pigs during the observatory period. CONCLUSIONS Endoscopic muscular resection using a ligation device enabled us to obtain large and thick muscle tissue samples. This approach may facilitate more precise histological assessments of functional gastrointestinal disorders.
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Affiliation(s)
- Osamu Goto
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Kazutoshi Higuchi
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Atsushi Tatsuguchi
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Eriko Koizumi
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Hiroto Noda
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Takeshi Onda
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Jun Omori
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Mitsuru Kaise
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
| | - Katsuhiko Iwakiri
- Department of Gastroenterology and Hepatology, Nippon Medical School Hospital
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26
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Chen S, Zhang M, Liang M, Tan N, Cui Y, Wang J, Xin X, Ye Z, Zhuang Q, Xiao Y. The Number of Interstitial Cells of Cajal Differs Among Different Subtypes of Achalasia and is Related to Patients' Prognosis. Clin Transl Gastroenterol 2021; 12:e00388. [PMID: 34428185 PMCID: PMC8386899 DOI: 10.14309/ctg.0000000000000388] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 07/08/2021] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Achalasia is a primary esophageal motility disorder with heterogeneous manometric subtypes and prognosis, characterized by degeneration of the esophageal myenteric plexus, and reduction in interstitial cells of Cajal (ICCs). This study aimed to explore the histopathologic characteristics of lower esophageal sphincter (LES) muscle from patients with achalasia with different subtypes and different prognosis. METHODS We examined specimens of LES muscle from 122 patients with achalasia who underwent peroral endoscopic myotomy and from 10 control patients who underwent esophagectomy for esophageal cancer. Hematoxylin-eosin staining was performed to assess inflammation infiltration, fibrosis, and atrophy. Specific immunohistochemical staining was performed to identify ICCs and neuronal nitric oxide synthase (nNOS). RESULTS The number of ICCs in patients with type I achalasia was significantly lower than that in patients with type II achalasia, followed by that in control patients (type I vs type II vs control group= 0.4 vs 1.2 vs 9.5; P < 0.001). The number of nNOS-positive cells was significantly lower in patients with achalasia than that in control patients (type I vs type II vs control group = 0.0 vs 0.0 vs 8.0; P < 0.001). Nonrecurrent group had significantly more ICCs than recurrent group (type I: nonrecurrent vs recurrent = 1.0 vs 0.1; P = 0.010; type II: nonrecurrent vs recurrent = 2.0 vs 0.4; P = 0.004). DISCUSSION ICCs and nNOS-positive cells reduced significantly in LES muscle of patients with achalasia. The number of ICCs differed among different achalasia subtypes and was related to patients' clinical prognosis.
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Affiliation(s)
- Songfeng Chen
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Mengyu Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Mengya Liang
- Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Niandi Tan
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Yi Cui
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Jinhui Wang
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Xiangbin Xin
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Ziyin Ye
- Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Qianjun Zhuang
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
| | - Yinglian Xiao
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
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Mari A, Abu Baker F, Pellicano R, Khoury T. Diagnosis and Management of Achalasia: Updates of the Last Two Years. J Clin Med 2021; 10:3607. [PMID: 34441901 PMCID: PMC8397142 DOI: 10.3390/jcm10163607] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Achalasia is a rare neurodegenerative disorder causing dysphagia and is characterized by abnormal esophageal motor function as well as the loss of lower esophageal sphincter (LES) relaxation. The assessment and management of achalasia has significantly progressed in recent years due to the advances in high-resolution manometry (HRM) technology along with the improvements and innovations of therapeutic endoscopy procedures. The recent evolution of HRM technology with the inclusion of an adjunctive test, fluoroscopy, and EndoFLIP has enabled more precise diagnoses of achalasia to be made and the subgrouping into therapeutically meaningful subtypes. Current management possibilities include endoscopic treatments such as Botulinum toxin injected to the LES and pneumatic balloon dilation. Surgical treatment includes laparoscopic Heller myotomy and esophagectomy. Furthermore, in recent years, per oral endoscopic myotomy (POEM) has established itself as a principal endoscopic therapeutic alternative to the traditional laparoscopic Heller myotomy. The latest randomized trials report that POEM, pneumatic balloon dilatation, and laparoscopic Heller's myotomy have comparable effectiveness and complications rates. The aim of the current review is to provide a practical clinical approach to dysphagia and to shed light on the most recent improvements in diagnostics and treatment of achalasia over the last two years.
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Affiliation(s)
- Amir Mari
- Department of Gastroenterology, Nazareth Hospital, Faculty of Medicine, Bar-Ilan University, Safed 16100, Israel
| | - Fadi Abu Baker
- Hillel Yaffe Medical Center, Department of Gastroenterology and Hepatology, Hadera 38100, Israel;
| | | | - Tawfik Khoury
- Galilee Medical Center, Department of Gastroenterology, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 13100, Israel;
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Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures. Sci Rep 2021; 11:15889. [PMID: 34354183 PMCID: PMC8342505 DOI: 10.1038/s41598-021-95434-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 07/26/2021] [Indexed: 11/12/2022] Open
Abstract
Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remain unclear. Therefore, we aimed to examine ENSC integration using an adapted ex vivo organotypic culture system. Donor ENSC were obtained from Wnt1cre/+;R26RYFP/YFP mice allowing specific labelling, selection and fate-mapping of cells. YFP+ neurospheres were transplanted to C57BL6/J (6–8-week-old) colonic tissue and maintained in organotypic culture for up to 21 days. We analysed and quantified donor cell integration within recipient tissues at 7, 14 and 21 days, along with assessing the structural and molecular consequences of ENSC integration. We found that organotypically cultured tissues were well preserved up to 21-days in ex vivo culture, which allowed for assessment of donor cell integration after transplantation. Donor ENSC-derived cells integrated across the colonic wall in a dynamic fashion, across a three-week period. Following transplantation, donor cells displayed two integrative patterns; longitudinal migration and medial invasion which allowed donor cells to populate colonic tissue. Moreover, significant remodelling of the intestinal ECM and musculature occurred upon transplantation, to facilitate donor cell integration within endogenous enteric ganglia. These results provide critical evidence on the timescale and mechanisms, which regulate donor ENSC integration, within recipient gut tissue, which are important considerations in the future clinical translation of stem cell therapies for enteric disease.
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Oldfield EC, Parekh PJ, Johnson DA. Diagnosis and Treatment of Esophageal Chest Pain. THE ESOPHAGUS 2021:18-37. [DOI: 10.1002/9781119599692.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Muller K, Xiao J, Putra J, Rothstein R, McCourt C, Konnikova L, Lisovsky M. Lymphocytic Esophagitis With Predominance of CD4 T Cells and Expansion of Th1 Cells Is Associated With Achalasia. Am J Clin Pathol 2021; 156:278-287. [PMID: 33609026 PMCID: PMC12096299 DOI: 10.1093/ajcp/aqaa239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES Although histologic features in biopsies suggesting a possibility of achalasia would be helpful diagnostically, such features remain unknown. The goal of this study was to explore the prevalence, histologic features, and immunophenotype of lymphocytic esophagitis (LyE) in achalasia biopsies. METHODS The study group consisted of 57 patients with achalasia. Controls comprised 52 patients with severe gastroesophageal reflux disease (GERD) and normal esophageal motility. CD4/CD8 immunophenotype of lymphocytes was analyzed by immunohistochemistry. RESULTS LyE was identified in 30% (17/57) of patients with achalasia and 6% (3/52) of patients with GERD, indicating a strong association with achalasia (odds ratio, 6.94; 95% confidence interval, 1.90-25.38). LyE was focal in 59% (10/17) of the cases and diffuse in 41% (7/17). CD4 T-cell predominance over CD8 T cells was observed in 88% of patients with achalasia and LyE. T helper 1 (Th1) cells, but not T helper 2 cells, were expanded in CD4 T cells; in the absence of evident infection, this was compatible with the role of Th1 cells in organ-specific autoimmunity. CONCLUSIONS Achalasia should be considered in the differential diagnosis of clinical entities associated with CD4-predominant LyE. Additional studies to explore the significance of Th1 cells in achalasia-associated LyE are warranted.
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Affiliation(s)
- Kristen Muller
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Jenny Xiao
- Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Juan Putra
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Richard Rothstein
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Collin McCourt
- Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Liza Konnikova
- Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
- Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Mikhail Lisovsky
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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31
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Tabaeian SP, Anushiravani A, Fazlollahi N, Asl Soleimani H, Mikaeli J. Comparison of Treatment Response in Different Types of Achalasia: A Long-Term Study. Middle East J Dig Dis 2021; 13:186-192. [PMID: 36606219 PMCID: PMC9489460 DOI: 10.34172/mejdd.2021.224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 05/10/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Three manometric patterns are seen in high-resolution manometry (HRM). Response to treatment has been reported to be different in these subtypes. We aimed to investigate the frequency and response to treatment in subtypes of achalasia. METHODS 306 patients between 15 to 60 years old, naïve to treatment with idiopathic achalasia (IA) were evaluated prospectively in a cohort study for 8 years. The patients were treated with pneumatic balloon dilation (PBD), and evaluated before and one month after PBD with Achalasia Symptom Score (ASS) and timed barium esophagogram (TBE) and then every 6 months with ASS. The primary study outcome was defined as a reduction in ASS (equal to or less than 4) and a reduction greater than 80% in the volume of barium in TBE at 1 month after PBD compared with baseline values. RESULTS According to HRM, 57 were classified as type I (18.62%), 223 as type II (72.9%), and 26 as type III (8.5%). The mean lower esophageal sphincter (LES) residual pressures before treatment were 34.05 ± 31.55, 32.99 ± 17.90, and 37.47 ± 14.07 mmHg in types I, II, and III, respectively (p = 0.18). The mean ASS values before treatment were 12.23, 11.50, and 11.50, for types I, II, and III, respectively (p = 0.29). The ASS dropped to 2.50 in type I, 2.40 in type II, and 2.12 in type III at 1 month after treatment (p = 0.83). Eventually, at the end of follow-up, 24 patients with type I (83%), 82 patients with type II (67%), and five patients with type III (83%) showed sustained good responses (p = 0.528). CONCLUSION Manometric subtypes of achalasia did not have an important role in clinical success in the long term. Achalasia has no definite cure, but with current treatment modalities, palliation of symptoms is possible in over 90% of patients.
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Affiliation(s)
- Seidamir Pasha Tabaeian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
,Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Anushiravani
- Assistant professor of medicine, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Narges Fazlollahi
- Medical physician, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Asl Soleimani
- Associate Professor of Medicine, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Javad Mikaeli
- Professor of Medicine, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital: Karegar Shomali Ave, Tehran, Iran
,Corresponding Author: Javad Mikaeli, MD Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital: Karegar Shomali Ave, Tehran, Iran, postal code: 14117- 13135 Tel: + 98 21 82415000 Fax: + 98 21 82415400
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32
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Per-oral Endoscopic Myotomy Biopsies of Achalasia Patients Reveal Schwann Cell Depletion in the Muscularis Propria. Clin Gastroenterol Hepatol 2021; 19:1294-1295. [PMID: 32668343 DOI: 10.1016/j.cgh.2020.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/01/2020] [Accepted: 07/01/2020] [Indexed: 02/07/2023]
Abstract
Achalasia is a neurodegenerative condition resulting in abnormal lower esophageal sphincter relaxation and impaired upstream esophageal body peristalsis.1 The pathophysiology and natural history of achalasia remain unclear, and evaluation of the histopathogenesis of achalasia has traditionally been challenging because the esophageal wall muscularis propria is not typically accessible via routine endoscopic biopsies.
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33
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Achem SR, Vazquez-Elizondo G, Fass R. Jackhammer Esophagus: Current Concepts and Dilemmas. J Clin Gastroenterol 2021; 55:369-379. [PMID: 33337637 DOI: 10.1097/mcg.0000000000001472] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/23/2020] [Indexed: 12/27/2022]
Abstract
Jackhammer esophagus (JE) is a recently recognized esophageal motility disorder that is characterized by hypercontractile peristalsis. More than 500 cases have been reported in the literature. Among patients referred for esophageal motility disorders, the prevalence of JE ranges from 0.42% to 9%, with most series describing a prevalence of 2% to 4%. Most cases are women (60.5%). The mean reported age of patients with JE is 65.2 years, and patients commonly have dysphagia (62.8%). Reflux symptoms occur in ∼40% of patients, and chest pain affects more than one-third of patients (36.4%). JE is a heterogenous disorder that is associated with several conditions, including obesity, opioid use, lung transplantation, eosinophilic infiltration of the esophagus, neoplasia, and systemic diseases. The cause and pathogenesis remain unknown, but several observations suggest that it is the result of multiple conditions that likely precipitate increased excitation and abnormal inhibition of neuromuscular function. The natural course of JE also is unknown, but progression to achalasia has been observed in a few patients. Treatment is challenging, in part because of the insufficient understanding of the disorder's underlying mechanisms. Various therapeutic modalities have been used, ranging from observation only to pharmacologic and endoscopic interventions (eg, botulinum toxin injection) to peroral endoscopic myotomy. Treatment efficacy remains largely anecdotal and insufficiently studied.
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Affiliation(s)
- Sami R Achem
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | | | - Ronnie Fass
- Division of Gastroenterology and Hepatology, Metro Health Medical Center, Cleveland, OH
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34
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Nelson M, Zhang X, Genta RM, Turner K, Podgaetz E, Paris S, Cardenas J, Gu J, Leeds S, Ward M, Nguyen A, Konda V, Furuta GT, Pan Z, Souza RF, Spechler SJ. Lower esophageal sphincter muscle of patients with achalasia exhibits profound mast cell degranulation. Neurogastroenterol Motil 2021; 33:e14055. [PMID: 33280206 DOI: 10.1111/nmo.14055] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/23/2020] [Accepted: 11/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Eosinophils and mast cells are key effectors of allergy. When they accumulate in the esophagus, their myoactive, pro-inflammatory, and cytotoxic products potentially could cause achalasia-like motility abnormalities and neuronal degeneration. We hypothesized that there is an allergy-mediated form of achalasia. METHODS LES muscle samples obtained during Heller myotomy from patients with achalasia or EGJ outflow obstruction (EGJOO) and from organ donor controls were immunostained for tryptase. Eosinophil and mast cell density, and mast cell degranulation were assessed. LES muscle was evaluated by qPCR for genes mediating smooth muscle Ca2+ handling and contraction. KEY RESULTS There were 13 patients (7 men, median age 59; 10 achalasia, 3 EGJOO) and 7 controls (4 men, median age 42). Eosinophils were infrequent in LES muscle, but mast cells were plentiful. Patients and controls did not differ significantly in LES mast cell density. However, 12 of 13 patients exhibited profound LES mast cell degranulation involving perimysium and myenteric plexus nerves, while only mild degranulation was seen in 2 of 7 controls. Hierarchical clustering analysis of qPCR data revealed two "mototype" LES gene expression patterns, with all type II patients in one mototype, and type I and III patients in the other. CONCLUSIONS & INFERENCES LES muscle of patients with achalasia or EGJOO exhibits striking mast cell degranulation, and patients with different achalasia manometric phenotypes exhibit different LES patterns of expression for genes mediating Ca2+ handling and muscle contraction. Although these findings are not definitive, they support our hypothesis that achalasia can be allergy-driven.
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Affiliation(s)
- Melissa Nelson
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Xi Zhang
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Robert M Genta
- Inform Diagnostics, Irving, TX, USA.,Department of Pathology, Baylor College of Medicine, Houston, TX, USA
| | | | - Eitan Podgaetz
- Center for Thoracic Surgery, Center for Esophageal Diseases, Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Shere Paris
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Jacob Cardenas
- Biostatistics Core, Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Jinghua Gu
- Biostatistics Core, Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Steven Leeds
- Department of Surgery, Center for Esophageal Diseases, Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Marc Ward
- Department of Surgery, Center for Esophageal Diseases, Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Anh Nguyen
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Vani Konda
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Glenn T Furuta
- Department of Pediatrics and Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, CO, USA
| | - Zui Pan
- College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX, USA
| | - Rhonda F Souza
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
| | - Stuart Jon Spechler
- Department of Medicine, Center forEsophageal Diseases/Baylor University Medical Center, Center for Esophageal Research/Baylor Scott & White Research Institute, Dallas, TX, USA
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35
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Vackova Z, Mares J, Krajciova J, Rabekova Z, Zdrhova L, Loudova P, Spicak J, Stirand P, Hucl T, Martinek J. Esophageal Motility Patterns After Peroral Endoscopic Myotomy in Patients With Achalasia. J Neurogastroenterol Motil 2021; 27:205-214. [PMID: 33462158 PMCID: PMC8026367 DOI: 10.5056/jnm20126] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/28/2020] [Accepted: 09/20/2020] [Indexed: 01/16/2023] Open
Abstract
Background/Aims Several studies have reported partial recovery of peristalsis in patients with achalasia after myotomy. The aim of our study is to analyze esophageal motility patterns after peroral endoscopic myotomy (POEM) and to assess the potential predictors and clinical impact of peristaltic recovery. Methods We performed a retrospective analysis of prospectively collected data of consecutive patients with achalasia undergoing POEM at a tertiary center. High-resolution manometry (HRM) studies prior to and after POEM were reviewed and the Chicago classification was applied. Results A total of 237 patients were analyzed. The initial HRM diagnoses were achalasia type I, 42 (17.7%); type II, 173 (73.0%); and type III, 22 (9.3%). Before POEM, peristaltic fragments were present in 23 (9.7%) patients. After POEM the Chicago classification diagnoses were 112 absent contractility, 42 type I achalasia, 15 type II, 11 type III, 26 ineffective esophageal motility, 18 esophagogastric junction outflow obstruction, 10 fragmented peristalsis, and 3 distal esophageal spasm. Altogether 68 patients (28.7%) had signs of contractile activity, but the contractions newly appeared in 47 patients (47/214, 22.0%). Type II achalasia showed a trend for appearance of contractions (P = 0.097). Logistic regression analysis did not identify any predictors of peristaltic recovery. The post-POEM Eckardt score did not differ between patients with and without contractions nor did the parameters of timed barium esophagogram. Conclusions More than 20% of achalasia patients have signs of partial recovery of esophageal peristalsis after POEM. It occurs predominantly in type II achalasia but the clinical relevance seems to be negligible.
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Affiliation(s)
- Zuzana Vackova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jan Mares
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jana Krajciova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Zuzana Rabekova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Lucie Zdrhova
- Department of Internal Medicine, University Hospital Plzen, Czech Republic
| | - Pavla Loudova
- Department of Gastroenterology, Hospital Kolin, Czech Republic; and 5Ostrava University, Faculty of Medicine, Ostrava, Czech Republic
| | - Julius Spicak
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Petr Stirand
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Tomas Hucl
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jan Martinek
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
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36
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Wu XY, Liu ZQ, Wang Y, Chen WF, Gao PT, Li QL, Zhou PH. The etiology of achalasia: An immune-dominant disease. J Dig Dis 2021; 22:126-135. [PMID: 33583137 DOI: 10.1111/1751-2980.12973] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 02/09/2021] [Accepted: 02/10/2021] [Indexed: 02/06/2023]
Abstract
There is accumulating evidence suggesting that an autoimmune component is involved in esophageal achalasia. An increase in immune cells, cytokines, chemokines, and autoimmune antibodies in serum and infiltration of immune cells in tissues support the view that immune-mediated inflammation is a crucial pathogenesis of inhibitory neuron degeneration in the lower esophageal sphincter. Infection of viruses such as the herpes virus family has been suspected of provoking the autoimmune reaction. Meanwhile, previous reports on immunogenetics have proposed that specific risk alleles on the human leukocyte antigen complex define the susceptible population to achalasia. In this study we reviewed current knowledge regarding the immune-related factors of achalasia, including immunology, viral infection and immunogenetic variations.
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Affiliation(s)
- Xing Yue Wu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Medical College, Fudan University, Shanghai, China
| | - Zu Qiang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yun Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wei Feng Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping Ting Gao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Quan Lin Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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37
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Schizas D, Syllaios A, Vailas M, Sotiropoulou M, Triantafyllou T, Tsapralis D, Papanikolaou IS, Theodorou D. Eosinophilic Esophagitis and Achalasia: Two Distinct Nosologic Entities or a Possible Etiopathogenic Association? Dig Dis 2021; 39:553-560. [PMID: 33647902 DOI: 10.1159/000515520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 02/26/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Despite the fact that researchers have made significant progress in elucidating the pathophysiology of esophageal diseases, the understanding of esophageal motility alterations in patients with eosinophilic esophagitis (EoE) is in its infancy and current published medical literature remains rather scarce on this topic. A growing body of scientific data regarding associations between esophageal motor disorders, such as achalasia and EoE, exists nowadays. SUMMARY It seems that the association of EoE and achalasia does not constitute a cause and effect relationship, as it is not clear whether esophageal motility abnormalities are the result of EoE or vice versa. As such, there is no universally accepted treatment algorithm for patients presenting with both of these entities. Key Messages: The aim of this article is to review the existing data on achalasia-like motility disorders in patients with EoE, highlighting a possible association between these 2 esophageal disorders. Moreover, we seek to describe the clinical presentation in such cases, diagnostic modalities to be used, and current treatment strategies in patients suspected to suffer from both disorders.
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Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Athanasios Syllaios
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Michail Vailas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Maria Sotiropoulou
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Tania Triantafyllou
- First Propedeutic Department of Surgery, National and Kapodistrian University of Athens, Hippocration General Hospital, Athens, Greece
| | | | - Ioannis S Papanikolaou
- Hepatogastroenterology Unit, Second Department of Internal Medicine and Research Institute, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Dimitrios Theodorou
- First Propedeutic Department of Surgery, National and Kapodistrian University of Athens, Hippocration General Hospital, Athens, Greece
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38
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Rieder E, Fernandez-Becker NQ, Sarosiek J, Guillaume A, Azagury DE, Clarke JO. Achalasia: physiology and diagnosis. Ann N Y Acad Sci 2020; 1482:85-94. [PMID: 33140485 DOI: 10.1111/nyas.14510] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 09/17/2020] [Accepted: 09/22/2020] [Indexed: 12/18/2022]
Abstract
Achalasia is a rare motility disorder with incomplete relaxation of the lower esophageal sphincter and ineffective contractions of the esophageal body. It has been hypothesized that achalasia does not result from only one pathway but rather involves a combination of infectious, autoimmune, and familial etiological components. On the basis of other observations, a novel hypothesis suggests that a muscular form of eosinophilic esophagitis is involved in the pathophysiology of achalasia in some patients. This appears to progressively diminish the myenteric plexus at stage III, gradually destroy it at stage II, and finally eliminate it at stage I, the most advanced and final stage of achalasia. Although high-resolution manometry has identified these three different types of achalasia, another subset of patients with a normal-appearing sphincter relaxation has been proposed. Provocative maneuvers, such as the rapid drinking challenge, have recently been demonstrated to improve diagnosis in certain borderline patients, but have to be studied in more detail. However, whether the different types of achalasia will have a long-term impact on tailored therapies is still a matter of debate. Additionally, novel aspects of the standard timed barium swallow appear to be an important adjunct of diagnosis, as it has been shown to have a diagnostic as well as a predictive value.
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Affiliation(s)
- Erwin Rieder
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | | | - Jerzy Sarosiek
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas
| | - Alexandra Guillaume
- Gastrointestinal Motility Center, Renaissance School of Medicine, Stony Brook University Hospital, Stony Brook, New York
| | - Dan E Azagury
- Minimally Invasive & Bariatric Surgery, Stanford University School of Medicine, Palo Alto, California
| | - John O Clarke
- Department of Medicine, Stanford University, Redwood City, California
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39
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Chen WF, Liu ZQ, Pu ZN, Xu JQ, Yao L, Wu XY, Xu XY, Xu JX, Zhu Y, Wang Y, Cheng J, Zhu L, Zhou PH, Li QL. Multiplex immunoassays reveal increased serum cytokines and chemokines associated with the subtypes of achalasia. Neurogastroenterol Motil 2020; 32:e13832. [PMID: 32134545 DOI: 10.1111/nmo.13832] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 02/15/2020] [Accepted: 02/18/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-ß1 (P < .001), TGF-ß2 (P < .001), TGF-ß3 (P < .001), IL-1ra (P < .001), IL-17 (P = .005), IL-18 (P < .001), IFN-γ (P < .001), MIG (P < .001), PDGF-BB (P < .001), IP-10 (P = .003), and SCGF-B (P < .001). Gene ontology (GO) and network functional enrichment analysis revealed regulation of signaling receptor activity and receptor-ligand activity were the most related pathways of these cytokines and chemokines. Levels of twelve cytokines and chemokines were significantly increased in type III compared with I/II achalasia, namely, TGF-ß2, IL-1ra, IL-2Ra, IL-18, MIG, IFN-γ, SDF-1a, Eotaxin, PDGF-BB, IP-10, MCP-1, and TRAIL. CONCLUSIONS AND INFERENCES Patients with achalasia exhibited increased levels of serological cytokines and chemokines. Levels of cytokines and chemokines were significantly increased in type III than in type I/II achalasia. Cytokines and chemokines might contribute to the inflammatory development of achalasia.
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Affiliation(s)
- Wei-Feng Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zu-Qiang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhe-Ning Pu
- Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Jia-Qi Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lu Yao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | - Xiao-Yue Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia-Xin Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yan Zhu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yun Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jing Cheng
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Liang Zhu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping-Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Quan-Lin Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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40
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Jung HK, Hong SJ, Lee OY, Pandolfino J, Park H, Miwa H, Ghoshal UC, Mahadeva S, Oshima T, Chen M, Chua ASB, Cho YK, Lee TH, Min YW, Park CH, Kwon JG, Park MI, Jung K, Park JK, Jung KW, Lim HC, Jung DH, Kim DH, Lim CH, Moon HS, Park JH, Choi SC, Suzuki H, Patcharatrakul T, Wu JCY, Lee KJ, Tanaka S, Siah KTH, Park KS, Kim SE. 2019 Seoul Consensus on Esophageal Achalasia Guidelines. J Neurogastroenterol Motil 2020; 26:180-203. [PMID: 32235027 PMCID: PMC7176504 DOI: 10.5056/jnm20014] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 03/08/2020] [Indexed: 12/13/2022] Open
Abstract
Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the "2019 Seoul Consensus on Esophageal Achalasia Guidelines") were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - John Pandolfino
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Hyojin Park
- Division of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sanjiv Mahadeva
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Yu Kyung Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, College of Medicine, Soonchunhyang University Hospital, Seoul, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Kyoungwon Jung
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Jong Kyu Park
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Hyun Lim
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Suck Chei Choi
- Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Korea
| | - Hidekazu Suzuki
- Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Tanisa Patcharatrakul
- Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
| | - Shinwa Tanaka
- Department of Gastroenterology, Kobe University Hospital, Hyogo, Japan
| | - Kewin T H Siah
- Division of Gastroenterology and Hepatology, National University Health System, Singapore City, Singapore
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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Diaz-Oliva SE, Aguilera-Matos I, Villa Jiménez OM, Escobedo AA. Oesophageal eosinophilia and oesophageal diseases in children: are the limits clear? BMJ Paediatr Open 2020; 4:e000680. [PMID: 32818156 PMCID: PMC7406026 DOI: 10.1136/bmjpo-2020-000680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/01/2020] [Accepted: 07/05/2020] [Indexed: 12/16/2022] Open
Abstract
Gastro-oesophageal reflux disease, eosinophilic oesophagitis and oesophageal motility disorders are among the most common diseases accompanying oesophageal eosinophilia. They have similarities and their limits are frequently not well defined. This article reviews the main characteristics relating to their similarities and differences, highlighting existing controversies among these diseases, in addition to current knowledge. In the case of a patient with symptoms of oesophageal dysfunction, it is suggested to carry out an integral analysis of the clinical features and diagnostic test results, including histology, while individualising each case before confirming a definitive diagnosis. Future investigation in paediatric patients is necessary to assess eosinophilic infiltration in the various layers of the oesophageal tissue, along with its clinical and pathophysiological implications.
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Affiliation(s)
| | | | | | - Angel A Escobedo
- Pediatric Gastroentrology, Institute of Gastroenterology, Havana, Cuba.,Research department, Epidemiology, Institute of Gastroenterology, Havana, Cuba
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Nikaki K, Sawada A, Ustaoglu A, Sifrim D. Neuronal Control of Esophageal Peristalsis and Its Role in Esophageal Disease. Curr Gastroenterol Rep 2019; 21:59. [PMID: 31760496 DOI: 10.1007/s11894-019-0728-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
PURPOSE OF REVIEW Esophageal peristalsis is a highly sophisticated function that involves the coordinated contraction and relaxation of striated and smooth muscles in a cephalocaudal fashion, under the control of central and peripheral neuronal mechanisms and a number of neurotransmitters. Esophageal peristalsis is determined by the balance of the intrinsic excitatory cholinergic, inhibitory nitrergic and post-inhibitory rebound excitatory output to the esophageal musculature. RECENT FINDINGS Dissociation of the longitudinal and circular muscle contractions characterizes different major esophageal disorders and leads to esophageal symptoms. Provocative testing during esophageal high-resolution manometry is commonly employed to assess esophageal body peristaltic reserve and underpin clinical diagnosis. Herein, we summarize the main factors that determine esophageal peristalsis and examine their role in major and minor esophageal motility disorders and eosinophilic esophagitis.
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Affiliation(s)
- K Nikaki
- Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, 26 Ashfield Street, Whitechapel, London, E1 2AJ, UK
| | - A Sawada
- Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, 26 Ashfield Street, Whitechapel, London, E1 2AJ, UK
| | - A Ustaoglu
- Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, 26 Ashfield Street, Whitechapel, London, E1 2AJ, UK
| | - D Sifrim
- Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, 26 Ashfield Street, Whitechapel, London, E1 2AJ, UK.
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Midya S, Ghosh D, Mahmalat MW. Fundoplication in laparoscopic Heller's cardiomyotomy for achalasia. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2019. [DOI: 10.1002/14651858.cd013386] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Sumit Midya
- Royal Berkshire Hospital; Department of General Surgery; Reading UK RG1 5AN
| | - Debasish Ghosh
- Royal Berkshire Hospital; Department of General Surgery; Reading UK RG1 5AN
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Schizas D, Kapsampelis P, Tsilimigras DI, Kanavidis P, Moris D, Papanikolaou IS, Karamanolis GP, Theodorou D, Liakakos T. The 100 most cited manuscripts in esophageal motility disorders: a bibliometric analysis. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:310. [PMID: 31475180 PMCID: PMC6694239 DOI: 10.21037/atm.2019.06.34] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 05/10/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The use of bibliometrics can help us identify the most impactful articles on a topic or scientific discipline and their influence on clinical practice. We aimed to identify the 100 most cited articles covering esophageal motility disorders and examine their key characteristics. METHODS The Web of Science database was utilized to perform the search, using predefined search terms. The returned dataset was filtered to include full manuscripts written in the English language. After screening, we identified the 100 most cited articles and analyzed them for title, year of publication, names of authors, institution, country of the first author, number of citations and citation rate. RESULTS The initial search returned 29,521 results. The top 100 articles received a total of 20,688 citations. The most cited paper was by Inoue et al. (665 citations) who first described peroral endoscopic myotomy (POEM) for treating achalasia. The article with the highest citation rate was the third version of the Chicago Classification system, written by Kahrilas and colleagues. Gastroenterology published most papers on the list (n=32) and accrued the highest number of citations (6,675 citations). Peter Kahrilas was the most cited author (3,650 citations) and, along with Joel Richter, authored the highest number of manuscripts (n=14). Most articles were produced in the USA (n=66) between the years 1991 and 2000 (n=32). CONCLUSIONS By analyzing the most influential articles, this work is a reference on the articles that shaped our understanding of esophageal motility disorders, thus serving as a guide for future research.
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Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Panagiotis Kapsampelis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Diamantis I. Tsilimigras
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Prodromos Kanavidis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Ioannis S. Papanikolaou
- Hepatogastroenterology Unit, Second Department of Internal Medicine and Research Institute, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Georgios P. Karamanolis
- Gastroenterology Unit, Second Department of Surgery, National and Kapodistrian University of Athens, Aretaieio University Hospital, Athens, Greece
| | - Dimitrios Theodorou
- First Propedeutic Department of Surgery, National and Kapodistrian University of Athens, Hippocration General Hospital, Athens, Greece
| | - Theodore Liakakos
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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45
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Kim GH, Jung KW. [Emerging Issues in Esophageal Motility Diseases]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2019; 73:322-326. [PMID: 31234622 DOI: 10.4166/kjg.2019.73.6.322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 05/23/2019] [Accepted: 05/23/2019] [Indexed: 01/07/2023]
Abstract
With the advances in technology and medical knowledge, new diseases are being identified and investigated. Esophageal motility disorders have been re-defined using high-resolution manometry and their pathogenesis are being better understood. The use of opioid analgesics is increasing worldwide, particularly in the United States, but their chronic use can cause opioid-induced esophageal dysfunction, which mimics spastic motor disorders, including achalasia type 3 or 2 and esophagogastric junction outflow obstruction. Eosinophilic esophagitis is identified by eosinophilic infiltration confirmed on a pathological examination. The condition is often associated with esophageal motility abnormalities. On the other hand, recent studies have suggested that muscle-predominant eosinophilic infiltration, eosinophilic esophageal myositis, might manifest as spastic motor disorders, including achalasia or jackhammer esophagus. Lymphocytic esophagitis is an unusual esophageal condition, which is confirmed by the increased number of lymphocytes in the esophageal epithelium. Although several reports have supported the existence of lymphocytic esophagitis, it is still unclear whether lymphocytic esophagitis is a distinct disease entity or another spectrum of other esophageal diseases, such as gastroesophageal reflux disease or eosinophilic esophagitis. This review presents evidence and reports on the emerging issues in esophageal motility disorders, including opioid-induced esophageal dysfunction, eosinophilic esophagitis with eosinophilic esophageal myositis, and lymphocytic esophagitis.
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Affiliation(s)
- Ga Hee Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Pallabazzer G, Peluso C, de Bortoli N, Solito B, D'Imporzano S, Belluomini MA, Bellomini MG, Giusti P, Gianetri D, Santi S. Clinical and pathophysiological outcomes of the robotic-assisted Heller-Dor myotomy for achalasia: a single-center experience. J Robot Surg 2019; 14:331-335. [PMID: 31230265 DOI: 10.1007/s11701-019-00988-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 06/17/2019] [Indexed: 12/12/2022]
Abstract
Laparoscopic Heller myotomy and Dor fundoplication is considered a safe and effective treatment for achalasia. Robotic-assisted Heller-Dor procedure (RAHD) has emerged as an alternative approach due to improved visualization and fine motor control. The aim of this prospective study was to evaluate clinical, and functional results of RAHD. We evaluated a group of 66 patients with achalasia that underwent robotic-assisted Heller-Dor operation. Before treatment all patients underwent a diagnostic work-up such as upper endoscopy, esophageal barium swallow and high resolution manometry. The presence of postoperative gastroesophageal reflux disease was diagnosed by impedance and pH monitoring (MII-pH). Dysphagia improved in 92.4% of patients after treatment. Barium swallow series showed esophageal emptying in 100% of patients and a significant reduction of the esophageal diameter (p = 0.00235). Forty-five of 66 patients (68.2%) underwent upper endoscopy and 35 of 66 (53%) underwent MII-pH. Esophageal erosions were found in 4/45 (8,8%) and MII-pH showed abnormal results in 3/35 patients (8.6%). RAHD ensures a meticulous esophageal and gastric myotomy, allowing to visualize and divide each muscle fibers with a low rate of intraoperative and postoperative complications. resulting in turn in good clinical outcomes, radiological findings and functional results even if robotic tecnique definitely increases the surgical cost in the treatment of these functional esophageal disorders.
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Affiliation(s)
- G Pallabazzer
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy.
| | - C Peluso
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
| | - N de Bortoli
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, AOUP, Pisa, Italy
| | - B Solito
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
| | - S D'Imporzano
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
| | - M A Belluomini
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
| | - M G Bellomini
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
| | - P Giusti
- Division of Radiology, Department of Radiology, Vascular and Interventional Radiology and Nuclear Medicine, AOUP, Pisa, Italy
| | - D Gianetri
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
| | - S Santi
- Unit of Esophageal Surgery, Department of Surgery, Azienda Ospedaliero Universitaria Pisana (AOUP), Via Paradisa 2, 56124, Pisa, Italy
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Nesteruk K, Spaander MCW, Leeuwenburgh I, Peppelenbosch MP, Fuhler GM. Achalasia and associated esophageal cancer risk: What lessons can we learn from the molecular analysis of Barrett's-associated adenocarcinoma? Biochim Biophys Acta Rev Cancer 2019; 1872:188291. [PMID: 31059738 DOI: 10.1016/j.bbcan.2019.04.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 04/02/2019] [Accepted: 04/29/2019] [Indexed: 02/08/2023]
Abstract
Idiopathic achalasia and Barrett's esophagus (BE) are preneoplastic conditions of the esophagus. BE increases the risk of esophageal adenocarcinoma (EAC), while achalasia is associated with both EAC and esophageal squamous cell carcinoma (ESCC). However, while the molecular mechanisms underlying the transformation of esophageal epithelial cells in BE are relatively well characterized, less is known regarding these processes in achalasia. Nevertheless, both conditions are associated with chronic inflammation and BE can occur in achalasia patients, and it is likely that similar processes underlie cancer risk in both diseases. The present review will discuss possible lessons that we can learn from the molecular analysis of BE for the study of achalasia-associated cancer and contrast findings in BE with those in achalasia. First, we will describe cellular fate during development of BE, EAC, and ESCC, and consider the inflammatory status of the epithelial barrier in BE and achalasia in terms of its contribution to carcinogenesis. Next, we will summarize current data on genetic alterations and molecular pathways involved in these processes. Lastly, the plausible role of the microbiota in achalasia-associated carcinogenesis and its contribution to abnormal lower esophageal sphincter (LES) functioning, the maintenance of chronic inflammatory status and influence on the esophageal mucosa through carcinogenic by-products, will be discussed.
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Affiliation(s)
- K Nesteruk
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - M C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - I Leeuwenburgh
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis, Rotterdam, the Netherlands
| | - M P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - G M Fuhler
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands..
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Liu ZQ, Chen WF, Wang Y, Xu XY, Zeng YG, Lee Dillon D, Cheng J, Xu MD, Zhong YS, Zhang YQ, Yao LQ, Zhou PH, Li QL. Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia. Neurogastroenterol Motil 2019; 31:e13565. [PMID: 30868687 DOI: 10.1111/nmo.13565] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 12/10/2018] [Accepted: 01/11/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune-mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia. METHODS We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS-positive cells, and S-100-positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups. KEY RESULTS Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS-positive cells, and S-100-positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS-positive cells, and S-100-positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040). CONCLUSIONS & INFERENCES In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.
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Affiliation(s)
- Zu-Qiang Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wei-Feng Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yun Wang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiao-Yue Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi-Gang Zeng
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dustin Lee Dillon
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Jing Cheng
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mei-Dong Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yun-Shi Zhong
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi-Qun Zhang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li-Qing Yao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping-Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Quan-Lin Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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Gao Y, Liu JF, He X, Liu XB, Zhang LL, Zhao LM, Zhang C. Calcium Receptor and Nitric Oxide Synthase Expression in Circular Muscle of Lower Esophagus from Patients with Achalasia. Chin Med J (Engl) 2019; 131:2882-2885. [PMID: 30511698 PMCID: PMC6278202 DOI: 10.4103/0366-6999.246081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Affiliation(s)
- Yang Gao
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011; Graduate School, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Jun-Feng Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
| | - Xin He
- Graduate School, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Xin-Bo Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
| | - Ling-Ling Zhang
- Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
| | - Lian-Mei Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
| | - Chao Zhang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
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Watanabe D, Tanaka S, Kawara F, Abe H, Ariyoshi R, Nakano Y, Takao T, Morita Y, Toyonaga T, Umegaki E, Kodama Y. Clinical impact of peroral endoscopic myotomy for esophageal motility disorders on esophageal muscle layer thickness. Endosc Int Open 2019; 7:E525-E532. [PMID: 31041369 PMCID: PMC6447396 DOI: 10.1055/a-0838-5268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Previously, we reported that esophageal muscle layer thickness was associated with technical complexity of peroral endoscopic myotomy (POEM). However, there are no data regarding the mid-term effects of POEM procedures on esophageal muscle layer thickness. Therefore, we conducted this study to elucidate mid-term effects of POEM procedures, and to examine whether postoperative changes in esophageal muscle layer thickness were related to particular clinico-pathological features in patients with esophageal motility disorders. Patients and methods Seventy-four consecutive patients with esophageal motility disorders who underwent POEM at Kobe University Hospital from April 2015 to December 2016 were prospectively recruited into this study. First, we investigated the esophageal muscle layer thickness values obtained at 1 year after POEM. Second, we evaluated the effects of a reduction in muscle layer thickness on various clinico-pathological features. Results At 1 year after POEM, mean thickness of the inner circular muscle at 0 cm, 5 cm, and 10 cm from the esophagogastric junction was 1.06 ± 0.45 mm, 0.99 ± 0.36 mm, and 0.97 ± 0.44 mm, respectively. Among all sites, muscle layer thickness had significantly decreased after POEM. However, univariate logistic regression analysis demonstrated that no clinical factors were associated with esophageal muscle layer thickness after POEM procedure. Conclusions We demonstrated for the first time that thickness of the esophageal muscle layer was significantly decreased after POEM. This result reveals that changes in esophageal muscle layer thickness caused by esophageal motility disorders are reversible.
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Affiliation(s)
- Daisuke Watanabe
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Shinwa Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Fumiaki Kawara
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Hirohumi Abe
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Ryusuke Ariyoshi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Yoshiko Nakano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Toshitatsu Takao
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Yoshinori Morita
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Takashi Toyonaga
- Department of Gastroenterology, Kobe University Hospital, Kobe, Japan
| | - Eiji Umegaki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University, Kobe, Japan
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