Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-resolution manometry and recently described analysis algorithms, summarized in the Chicago Classification, have increased the recognition of achalasia. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or with peristalsis. Any of these phenotypes could indicate achalasia; however, without a disease-specific biomarker, no manometric pattern is absolutely specific. Laboratory studies indicate that achalasia is an autoimmune disease in which esophageal myenteric neurons are attacked in a cell-mediated and antibody-mediated immune response against an uncertain antigen. This autoimmune response could be related to infection of genetically predisposed subjects with herpes simplex virus 1, although there is substantial heterogeneity among patients. At one end of the spectrum is complete aganglionosis in patients with end-stage or fulminant disease. At the opposite extreme is type III (spastic) achalasia, which has no demonstrated neuronal loss but only impaired inhibitory postganglionic neuron function; it is often associated with accentuated contractility and could be mediated by cytokine-induced alterations in gene expression. Distinct from these extremes is progressive plexopathy, which likely arises from achalasia with preserved peristalsis and then develops into type II achalasia and then type I achalasia. Variations in its extent and rate of progression are likely related to the intensity of the cytotoxic T-cell assault on the myenteric plexus. Moving forward, we need to integrate the knowledge we have gained into treatment paradigms that are specific for individual phenotypes of achalasia and away from the one-size-fits-all approach.
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PMID:The spectrum of achalasia: lessons from studies of pathophysiology and high-resolution manometry. 2397 23

High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular achalasia. It has become apparent that the cardinal feature of achalasia - impaired lower oesophageal sphincter (LES) relaxation - can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting achalasia criteria that also benefit from therapies formerly reserved for achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of achalasia and achalasia-like syndromes.
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PMID:Expert consensus document: Advances in the management of oesophageal motility disorders in the era of high-resolution manometry: a focus on achalasia syndromes. 2962 12