Materiały źródłowe

• #1 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10037292/

  Achalasia cardia, type of esophageal dynamic disorder, is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter. Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia, and is more likely to occur in the elderly. […] Although histological changes in the esophageal mucosa have long been considered part of the pathogenesis of achalasia cardia, recent studies have found that inflammation and genetic changes may also contribute to achalasia at the molecular level. Currently, the etiology and pathogenesis of achalasia cardia remain unclear; however, it is generally believed that the histological changes of the esophageal mucosa caused by the loss of esophageal nerve cell function play a key role in its pathophysiology. Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration.

• #2 Pathogenesis of achalasia cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3386318/

  Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. […] In secondary achalasia, the cause for the degeneration of esophageal nerve fibers is known. Pathophysiologically, achalasia is caused by loss of inhibitory ganglion cells in the myenteric plexus. Since the initial description, several studies have attempted to explore initiating agents that may cause the disease such as viral infection, other environmental factors, autoimmunity, and genetic factors. However, the exact pathogenesis of primary achalasia is still not known. […] The pathophysiology of achalasia is outlined in a simplified manner in Figure 1. In healthy esophagus, progressive delay in contractility of the lower esophageal muscles results from the presence of inhibitory neurotransmitters such as nitric oxide and its receptors in the lower esophagus. In the initial stage of the disease, degeneration of inhibitory nerve fibers in the esophagus results in unopposed action of excitatory neurotransmitter such as acetylcholine, which leads to high amplitude non-peristaltic contractions (not progressively delayed or simultaneous). This stage of achalasia is known as vigorous achalasia (average amplitude of contractions in lower esophagus 40 mmHg). Progressive loss of cholinergic neurons results in dilation and low amplitude simultaneous contractions in the esophageal body; this stage of achalasia is called classic achalasia.

• #3 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection.

• #4 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  Achalasia is a rare esophageal motor disorder characterized by selective loss of esophageal inhibitory neuronal function, particularly at the lower esophageal sphincter (LES), where unopposed contractile tone leads to incomplete LES relaxation following swallows. […] The pathophysiologic basis is hypothesized to be initiated by an environmental trigger, probably a viral infection, in genetically predisposed individuals. […] Given similar antigenic structure and an associated mimicry, antibodies formed against the environmental trigger cause inflammation and damage to esophageal neurons and ganglia. […] If this process results in neuronal death, classic achalasia features develop, with esophageal body aperistalsis and loss of LES relaxation. […] The primary neuronal abnormality in achalasia is a selective loss of inhibitory neurons in the myenteric plexus of the distal esophagus and LES, with consequent imbalance of excitatory and inhibitory activity.

• #5 The Pathogenesis and Management of Achalasia: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl14446

  Pathophysiologically, the loss of the inhibitory innervation of the esophagus can be due to either extrinsic or intrinsic causes. Extrinsic causes may include central nervous system (CNS) lesions involving the DMN or the vagal nerve fibers, while intrinsic loss may be due to loss of the inhibitory ganglion cells in the myenteric plexus. […] Studies suggest that the more likely neuronal abnormality in achalasia is the imbalance between the excitatory and inhibitory neurons of the myenteric plexus. […] However, unlike the intact excitatory innervation, many physiologic studies show either absent or abnormal inhibitory innervation in achalasia. […] Loss of inhibitory neurons as the primary pathology in idiopathic achalasia was further strengthened by studies on inhibitory neurotransmitters.

• #6 Pathogenesis of achalasia cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3386318/

  Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. […] In secondary achalasia, the cause for the degeneration of esophageal nerve fibers is known. Pathophysiologically, achalasia is caused by loss of inhibitory ganglion cells in the myenteric plexus. Since the initial description, several studies have attempted to explore initiating agents that may cause the disease such as viral infection, other environmental factors, autoimmunity, and genetic factors. However, the exact pathogenesis of primary achalasia is still not known. […] The pathophysiology of achalasia is outlined in a simplified manner in Figure 1. In healthy esophagus, progressive delay in contractility of the lower esophageal muscles results from the presence of inhibitory neurotransmitters such as nitric oxide and its receptors in the lower esophagus. In the initial stage of the disease, degeneration of inhibitory nerve fibers in the esophagus results in unopposed action of excitatory neurotransmitter such as acetylcholine, which leads to high amplitude non-peristaltic contractions (not progressively delayed or simultaneous). This stage of achalasia is known as vigorous achalasia (average amplitude of contractions in lower esophagus 40 mmHg). Progressive loss of cholinergic neurons results in dilation and low amplitude simultaneous contractions in the esophageal body; this stage of achalasia is called classic achalasia.

• #7 Pathogenesis of achalasia cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3386318/

  Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. […] In secondary achalasia, the cause for the degeneration of esophageal nerve fibers is known. Pathophysiologically, achalasia is caused by loss of inhibitory ganglion cells in the myenteric plexus. Since the initial description, several studies have attempted to explore initiating agents that may cause the disease such as viral infection, other environmental factors, autoimmunity, and genetic factors. However, the exact pathogenesis of primary achalasia is still not known. […] The pathophysiology of achalasia is outlined in a simplified manner in Figure 1. In healthy esophagus, progressive delay in contractility of the lower esophageal muscles results from the presence of inhibitory neurotransmitters such as nitric oxide and its receptors in the lower esophagus. In the initial stage of the disease, degeneration of inhibitory nerve fibers in the esophagus results in unopposed action of excitatory neurotransmitter such as acetylcholine, which leads to high amplitude non-peristaltic contractions (not progressively delayed or simultaneous). This stage of achalasia is known as vigorous achalasia (average amplitude of contractions in lower esophagus 40 mmHg). Progressive loss of cholinergic neurons results in dilation and low amplitude simultaneous contractions in the esophageal body; this stage of achalasia is called classic achalasia.

• #8 The Pathogenesis and Management of Achalasia: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl14446

  More recent studies, however, point to NO as the primary inhibitory neurotransmitter in the myenteric plexus. […] Human studies also suggest a significantly decreased or absent NO innervation in the myenteric plexus of patients with achalasia. […] There may be a spectrum of histopathological changes at different stages of achalasia. Early in the disease, there is myenteric inflammation with ganglionitis without ganglion cell loss or neural fibrosis. This is consistent with the previous studies showing intact number of myenteric ganglion cells in the early stage of achalasia. […] The disease then progresses to classic achalasia (types I and II) with progressive destruction of inhibitory neurons and neural fibrosis.

• #9 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Achalasia: The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. […] The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter. […] Numerous heterogeneous studies on the pathogenesis of achalasia have proved that achalasia is caused by the neurodegeneration in the LES. Neurodegeneration is defined as the selective loss of inhibitory neurons in the myenteric plexus of the distal esophagus. […] Taking account of all the established evidence involved in achalasia, we proposed a hypothesis on the pathogenesis which was plotted in the Figure, where susceptible individuals with genetic background, are affected by viruses or other environmental factors, which subsequently triggers an autoimmune response that involves many mediators such as cytokines, chemokines, autoantibodies, complements, and extracellular proteolytic enzymes.

• #10 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis/print

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection. A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. It has also been suggested that there may be an allergy-driven form of achalasia.

• #11 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10037292/

  Achalasia cardia, type of esophageal dynamic disorder, is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter. Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia, and is more likely to occur in the elderly. […] Although histological changes in the esophageal mucosa have long been considered part of the pathogenesis of achalasia cardia, recent studies have found that inflammation and genetic changes may also contribute to achalasia at the molecular level. Currently, the etiology and pathogenesis of achalasia cardia remain unclear; however, it is generally believed that the histological changes of the esophageal mucosa caused by the loss of esophageal nerve cell function play a key role in its pathophysiology. Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration.

• #12 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection.

• #13 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://www.wjgnet.com/2307-8960/full/v11/i8/1741.htm

  Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration. […] In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] A small amount of data suggests that eosinophils and mast cells may play a role in the development of achalasia and esophageal obstructive motility disorders. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, autoantibodies against sarcomeres are present in serum samples from patients with achalasia cardia, particularly in carriers of the HLA DQA1*0103 and DQB1*0603 alleles.

• #14 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection.

• #15 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  A localized decrease of inhibitory neurotransmitters (VIP and NO) in concert with unopposed excitatory activity results in abnormal LES relaxation and absence of orderly esophageal peristalsis. […] Two pathways have been proposed for neuronal dysfunction in achalasia. […] In the traditional pathway associated with classic achalasia, there is immune mediated destruction of myenteric neurons resulting in aperistalsis and abnormal LES relaxation. […] Evidence exists supporting an autoimmune basis for achalasia, where an antibody response to a common antigen, perhaps a virus, selectively knocks out esophageal autonomic control mechanisms at the myenteric plexus ganglia and neurons. […] Herpes simplex virus type I (HSV-1) has been proposed as an infectious trigger; other viruses implicated include measles and human papilloma virus.

• #16 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Herein we reviewed the characteristics of neurodegeneration of LES in achalasia and the precipitating factors involved in the process of neurodegeneration in order to deepen the understanding of achalasia and provide enlightenment for potential therapeutic targets of achalasia. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality. […] Therefore, genetic factors are involved in the occurrence and development of achalasia. […] The presence of viral infection in achalasia has been confirmed by multiple studies. […] When viral infection occurs in susceptible populations, inflammation and immunity might be activated and cause sustained damage to myenteric neurons of the distal esophagus.

• #17 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. It has also been suggested that there may be an allergy-driven form of achalasia.

• #18 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Herein we reviewed the characteristics of neurodegeneration of LES in achalasia and the precipitating factors involved in the process of neurodegeneration in order to deepen the understanding of achalasia and provide enlightenment for potential therapeutic targets of achalasia. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality. […] Therefore, genetic factors are involved in the occurrence and development of achalasia. […] The presence of viral infection in achalasia has been confirmed by multiple studies. […] When viral infection occurs in susceptible populations, inflammation and immunity might be activated and cause sustained damage to myenteric neurons of the distal esophagus.

• #19 Pathogenesis of achalasia cardia

  https://www.wjgnet.com/1007-9327/full/v18/i24/3050.htm

  Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. […] Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Downs syndrome and Parkinsons disease.

• #20 Esophageal achalasia – Wikipedia

  https://en.wikipedia.org/wiki/Esophageal_achalasia

  Autopsy and myotomy specimens have, on histological examination, shown an inflammatory response consisting of CD3/CD8-positive cytotoxic T lymphocytes, variable numbers of eosinophils and mast cells, loss of ganglion cells, and neurofibrosis; these events appear to occur early in achalasia. Thus, it seems there is an autoimmune context to achalasia, most likely caused by viral triggers. Other studies suggest hereditary, neurodegenerative, genetic and infective contributions.

• #21 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10037292/

  In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. Enteric herpes zoster virus, herpes simplex virus, measles, and human papillomavirus can impair the regulation of functional esophageal movement and LES control in patients with achalasia, but not in all patients with viral infections. […] A small amount of data suggests that eosinophils and mast cells may play a role in the development of achalasia and esophageal obstructive motility disorders. The aggregation of eosinophils and mast cells in the esophagus causes an increased concentration of inflammatory cytokines; this leads to fibrosis remodeling of the esophageal wall, ultimately causing esophageal dysfunction and related symptoms.

• #22 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://www.wjgnet.com/2307-8960/full/v11/i8/1741.htm

  Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration. […] In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] A small amount of data suggests that eosinophils and mast cells may play a role in the development of achalasia and esophageal obstructive motility disorders. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, autoantibodies against sarcomeres are present in serum samples from patients with achalasia cardia, particularly in carriers of the HLA DQA1*0103 and DQB1*0603 alleles.

• #23 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Studies have demonstrated the elevation of cytokines and chemokines in achalasia, suggesting that inflammation is an indispensable part of the pathogenesis of achalasia. […] A matched case-control study including 6769 patients with achalasia and 27 076 controls found that the incidence of autoimmune diseases in patients with achalasia was significantly higher than that in controls, supporting the hypothesis that achalasia has an autoimmune component.

• #24 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://www.wjgnet.com/2307-8960/full/v11/i8/1741.htm

  Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration. […] In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] A small amount of data suggests that eosinophils and mast cells may play a role in the development of achalasia and esophageal obstructive motility disorders. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, autoantibodies against sarcomeres are present in serum samples from patients with achalasia cardia, particularly in carriers of the HLA DQA1*0103 and DQB1*0603 alleles.

• #25 Achalasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/169974-overview

  Achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) in response to swallowing. The LES is hypertensive in about 50% of patients. These abnormalities cause a functional obstruction at the gastroesophageal junction (GEJ). […] Although much is known about the factors that contribute to achalasia, the exact pathogenesis remains unclear. Lower esophageal sphincter (LES) pressure and relaxation are regulated by excitatory (eg, acetylcholine, substance P) and inhibitory (eg, nitric oxide, vasoactive intestinal peptide) neurotransmitters. Persons with achalasia lack nonadrenergic, noncholinergic, inhibitory ganglion cells, causing an imbalance in excitatory and inhibitory neurotransmission. The result is a hypertensive nonrelaxed esophageal sphincter.

• #26 The Pathogenesis and Management of Achalasia: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl14446

  Pathophysiologically, the loss of the inhibitory innervation of the esophagus can be due to either extrinsic or intrinsic causes. Extrinsic causes may include central nervous system (CNS) lesions involving the DMN or the vagal nerve fibers, while intrinsic loss may be due to loss of the inhibitory ganglion cells in the myenteric plexus. […] Studies suggest that the more likely neuronal abnormality in achalasia is the imbalance between the excitatory and inhibitory neurons of the myenteric plexus. […] However, unlike the intact excitatory innervation, many physiologic studies show either absent or abnormal inhibitory innervation in achalasia. […] Loss of inhibitory neurons as the primary pathology in idiopathic achalasia was further strengthened by studies on inhibitory neurotransmitters.

• #27 Pathophysiology of achalasia and diffuse esophageal spasm : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo22.html

  Achalasia is the best understood example of an esophageal motility disorder and characterized by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter. […] The histopathology of achalasia involves inflammation of the myenteric plexus of the esophagus with diminution of ganglion cells. Significant reduction in nitric oxide synthase containing neurons has been demonstrated using immunohistochemical staining. […] Autoimmune, neurodegenerative, and viral etiologies have been implicated in the pathogenesis of achalasia. However, the exact cause has yet to be elucidated. […] Pharmacologic studies in achalasia patients support the selective loss of inhibitory, nitrergic neurons with preservation of cholinergic innervation. […] Animal models that include genetically engineered mice with targeted disruption of the gene encoding for the neuronal form of nitric oxide synthase and pharmacologic administration of inhibitors of nitric oxide substantiate the role of nitrergic denervation in achalasia.

• #28 Pathogenesis of Achalasia

  https://www.helicojournal.org/journal/view.php?number=249

  Achalasia is a rare esophageal motility disorder characterized by loss of myenteric neurons leading to aperistalsis of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). […] Achalasia may be an autoimmune disease targeting esophageal myenteric neurons with cell-mediated and antibody-mediated attack to an unidentified antigen. […] Initial immunologic reactions can begin in genetically predisposed persons who had viral infection, such as herpes simplex virus 1. […] The type of immune response and the intensity of the cytotoxic T-cell attack can determine the clinical presentation of the disease. […] Patients with Chicago Classification type III achalasia may present with chronic inflammation in the absence of neuronal loss, whereas patients with Chicago Classification type I or II achalasia present with a predominantly cytotoxic immune response with progressive loss of myenteric neurons. […] Further well controlled researches which reveal the unknown facts of pathogenesis are needed.

• #29 Pathogenesis of Achalasia

  https://www.helicojournal.org/journal/view.php?number=249

  Achalasia is a rare esophageal motility disorder characterized by loss of myenteric neurons leading to aperistalsis of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). […] Achalasia may be an autoimmune disease targeting esophageal myenteric neurons with cell-mediated and antibody-mediated attack to an unidentified antigen. […] Initial immunologic reactions can begin in genetically predisposed persons who had viral infection, such as herpes simplex virus 1. […] The type of immune response and the intensity of the cytotoxic T-cell attack can determine the clinical presentation of the disease. […] Patients with Chicago Classification type III achalasia may present with chronic inflammation in the absence of neuronal loss, whereas patients with Chicago Classification type I or II achalasia present with a predominantly cytotoxic immune response with progressive loss of myenteric neurons. […] Further well controlled researches which reveal the unknown facts of pathogenesis are needed.

• #30

  https://www.asge.org/home/resources/key-resources/blog/view/practical-solutions/2023/09/27/case-7–achalasia

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus of the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES) and loss of peristalsis in the distal esophagus. […] The etiology of primary achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor disorders similar or identical to primary achalasia (e.g., gastric carcinoma, Chagas Disease and sarcoidosis). […] Achalasia is diagnosed by high-resolution esophageal manometry. Typical findings include impaired relaxation of the LES, as evidenced by an elevated integrated relaxation pressure as well as abnormal peristalsis. Manometry findings of achalasia can be classified into three distinct subtypes: type I, with complete absence of peristalsis; type II, with pan-esophageal pressurization; and type III, with spastic peristalsis.

• #31 Pathogenesis of Achalasia

  https://www.helicojournal.org/journal/view.php?number=249

  Achalasia is a rare esophageal motility disorder characterized by loss of myenteric neurons leading to aperistalsis of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). […] Achalasia may be an autoimmune disease targeting esophageal myenteric neurons with cell-mediated and antibody-mediated attack to an unidentified antigen. […] Initial immunologic reactions can begin in genetically predisposed persons who had viral infection, such as herpes simplex virus 1. […] The type of immune response and the intensity of the cytotoxic T-cell attack can determine the clinical presentation of the disease. […] Patients with Chicago Classification type III achalasia may present with chronic inflammation in the absence of neuronal loss, whereas patients with Chicago Classification type I or II achalasia present with a predominantly cytotoxic immune response with progressive loss of myenteric neurons. […] Further well controlled researches which reveal the unknown facts of pathogenesis are needed.

• #32 The Pathogenesis and Management of Achalasia: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl14446

  More recent studies, however, point to NO as the primary inhibitory neurotransmitter in the myenteric plexus. […] Human studies also suggest a significantly decreased or absent NO innervation in the myenteric plexus of patients with achalasia. […] There may be a spectrum of histopathological changes at different stages of achalasia. Early in the disease, there is myenteric inflammation with ganglionitis without ganglion cell loss or neural fibrosis. This is consistent with the previous studies showing intact number of myenteric ganglion cells in the early stage of achalasia. […] The disease then progresses to classic achalasia (types I and II) with progressive destruction of inhibitory neurons and neural fibrosis.

• #33 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Achalasia: The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. […] The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter. […] Numerous heterogeneous studies on the pathogenesis of achalasia have proved that achalasia is caused by the neurodegeneration in the LES. Neurodegeneration is defined as the selective loss of inhibitory neurons in the myenteric plexus of the distal esophagus. […] Taking account of all the established evidence involved in achalasia, we proposed a hypothesis on the pathogenesis which was plotted in the Figure, where susceptible individuals with genetic background, are affected by viruses or other environmental factors, which subsequently triggers an autoimmune response that involves many mediators such as cytokines, chemokines, autoantibodies, complements, and extracellular proteolytic enzymes.

• #34 Pathogenesis of achalasia cardia

  https://www.wjgnet.com/1007-9327/full/v18/i24/3050.htm

  Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus. […] The pathophysiology of achalasia is outlined in a simplified manner in Figure 1. In healthy esophagus, progressive delay in contractility of the lower esophageal muscles results from the presence of inhibitory neurotransmitters such as nitric oxide and its receptors in the lower esophagus. […] Studies demonstrating reduction in number of ganglion cells in the esophageal body at autopsy of patients with achalasia and an inverse correlation between number of ganglion cells and duration of disease support their involvement in the disease process. […] All the above data suggest that achalasia results from degeneration of the esophageal nerve plexus, particularly the inhibitory fibers.

• #35 Pathogenesis of achalasia cardia

  https://www.wjgnet.com/1007-9327/full/v18/i24/3050.htm

  Achalasia is caused by loss of inhibitory ganglion in the myenteric plexus in the esophagus. Gradual progression of neuronal degeneration is associated with progression of the disease from vigorous to classic achalasia. Though several studies have attempted to explore initiating agents that may cause the disease, the exact factors responsible for the degeneration of ganglion cells in the myenteric plexus are poorly understood. The disease is likely to be multi-factorial involving host genetic factors, autoimmunity, and environmental factors such as infections. More studies are needed to explore the exact cause of this enigmatic disease.

• #36 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  The second pathway consists of immune mediated inflammatory injury that damages but does not kill the myenteric neurons, resulting in an imbalance between excitatory and inhibitory influences. […] This myenteric plexitis leads to exaggerated, premature and rapid esophageal body contraction, with or without esophageal outflow obstruction. […] In addition to traditional inflammatory pathways, eosinophilic inflammation has been identified in esophageal smooth muscle in some phenotypes of type 3 achalasia and EGJOO. […] This raises the question as to whether an allergic or hypersensitivity based mechanism underlies the pathophysiology of some achalasia phenotypes. […] Achalasia is an esophageal motor disorder where esophageal inhibitory function is irreversibly compromised, leading to abnormal LES relaxation and lack of effective esophageal body peristalsis. […] Current understanding of achalasia pathophysiology implicates an environmental insult, potentially viral, in a genetically predisposed individual, resulting in an antibody response that targets esophageal ganglia and neurons because of a shared antigenic structure with the insulting agent.

• #37 Pathogenesis of achalasia cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3386318/

  Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. […] In secondary achalasia, the cause for the degeneration of esophageal nerve fibers is known. Pathophysiologically, achalasia is caused by loss of inhibitory ganglion cells in the myenteric plexus. Since the initial description, several studies have attempted to explore initiating agents that may cause the disease such as viral infection, other environmental factors, autoimmunity, and genetic factors. However, the exact pathogenesis of primary achalasia is still not known. […] The pathophysiology of achalasia is outlined in a simplified manner in Figure 1. In healthy esophagus, progressive delay in contractility of the lower esophageal muscles results from the presence of inhibitory neurotransmitters such as nitric oxide and its receptors in the lower esophagus. In the initial stage of the disease, degeneration of inhibitory nerve fibers in the esophagus results in unopposed action of excitatory neurotransmitter such as acetylcholine, which leads to high amplitude non-peristaltic contractions (not progressively delayed or simultaneous). This stage of achalasia is known as vigorous achalasia (average amplitude of contractions in lower esophagus 40 mmHg). Progressive loss of cholinergic neurons results in dilation and low amplitude simultaneous contractions in the esophageal body; this stage of achalasia is called classic achalasia.

• #38

  https://www.asge.org/home/resources/key-resources/blog/view/practical-solutions/2023/09/27/case-7–achalasia

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus of the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES) and loss of peristalsis in the distal esophagus. […] The etiology of primary achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor disorders similar or identical to primary achalasia (e.g., gastric carcinoma, Chagas Disease and sarcoidosis). […] Achalasia is diagnosed by high-resolution esophageal manometry. Typical findings include impaired relaxation of the LES, as evidenced by an elevated integrated relaxation pressure as well as abnormal peristalsis. Manometry findings of achalasia can be classified into three distinct subtypes: type I, with complete absence of peristalsis; type II, with pan-esophageal pressurization; and type III, with spastic peristalsis.

• #39 Achalasia Cardia: A Comprehensive Review | EMJ Reviews

  https://www.emjreviews.com/gastroenterology/article/achalasia-cardia-a-comprehensive-review/

  Autoimmune degeneration is mediated by both cytotoxic T cells (cell-mediated immunity) and antibodies to enteric neurons and complement activation (humoral immunity). […] Achalasia cardia is associated with other neurodegenerative diseases like Parkinsons disease, as evidenced by the presence of Lewy bodies in ganglion cells. […] Achalasia, like oesophageal dysmotility, can be caused by ganglion cell degeneration by Trypanosoma cruzi, which causes Chagas disease (endemic in South America). […] The combination of achalasia, alacrima, and adrenal insufficiency is known as Allgrove syndrome, or triple A syndrome, which is a rare autosomal recessive disorder.

• #40 Achalasia Cardia: A Comprehensive Review | EMJ Reviews

  https://www.emjreviews.com/gastroenterology/article/achalasia-cardia-a-comprehensive-review/

  Autoimmune degeneration is mediated by both cytotoxic T cells (cell-mediated immunity) and antibodies to enteric neurons and complement activation (humoral immunity). […] Achalasia cardia is associated with other neurodegenerative diseases like Parkinsons disease, as evidenced by the presence of Lewy bodies in ganglion cells. […] Achalasia, like oesophageal dysmotility, can be caused by ganglion cell degeneration by Trypanosoma cruzi, which causes Chagas disease (endemic in South America). […] The combination of achalasia, alacrima, and adrenal insufficiency is known as Allgrove syndrome, or triple A syndrome, which is a rare autosomal recessive disorder.

• #41 Differences between idiopathic and chagasic achalasia

  https://www.oaepublish.com/articles/2574-1225.2017.25

  While in idiopathic achalasia neural destruction has been suggested to be more intense in inhibitory nerves than in excitatory nerves, in achalasia caused by Trypanosoma cruzi infection neural impairment involves both inhibitory and excitatory innervations. […] Consequently lower esophageal sphincter pressure is frequently increased in idiopathic achalasia and frequently decreased in Chagas disease which may explain the variation in the lower esophageal sphincter pressure, and the heterogeneity seen in these patients. […] Taken together, both Chagas disease-related and idiopathic achalasia have similar clinical and radiologic manifestations, including nonrelaxing or partially relaxing lower esophageal sphincter and esophageal aperistalsis, although the pathophysiology of the diseases should not be the same.

• #42

  https://www.asge.org/home/resources/key-resources/blog/view/practical-solutions/2023/09/27/case-7–achalasia

  Treatment of achalasia is focused on decreasing the LES pressure. Temporary relief can be achieved with endoscopic injection of botulinum toxin into the LES, typically lasting for three to six months. Definitive therapeutic options include pneumatic dilation with a large-diameter balloon under fluoroscopic guidance, peroral endoscopic myotomy (POEM) or Heller myotomy (laparoscopic or open surgery) with partial fundoplication. […] POEM, Heller myotomy with partial fundoplication, and pneumatic dilation are effective treatments for patients with type I and type II achalasia, whereas evidence suggests POEM is more effective in type III achalasia.

• #43

  https://www.asge.org/home/resources/key-resources/blog/view/practical-solutions/2023/09/27/case-7–achalasia

  Treatment of achalasia is focused on decreasing the LES pressure. Temporary relief can be achieved with endoscopic injection of botulinum toxin into the LES, typically lasting for three to six months. Definitive therapeutic options include pneumatic dilation with a large-diameter balloon under fluoroscopic guidance, peroral endoscopic myotomy (POEM) or Heller myotomy (laparoscopic or open surgery) with partial fundoplication. […] POEM, Heller myotomy with partial fundoplication, and pneumatic dilation are effective treatments for patients with type I and type II achalasia, whereas evidence suggests POEM is more effective in type III achalasia.

• #44

  https://www.asge.org/home/resources/key-resources/blog/view/practical-solutions/2023/09/27/case-7–achalasia

  Treatment of achalasia is focused on decreasing the LES pressure. Temporary relief can be achieved with endoscopic injection of botulinum toxin into the LES, typically lasting for three to six months. Definitive therapeutic options include pneumatic dilation with a large-diameter balloon under fluoroscopic guidance, peroral endoscopic myotomy (POEM) or Heller myotomy (laparoscopic or open surgery) with partial fundoplication. […] POEM, Heller myotomy with partial fundoplication, and pneumatic dilation are effective treatments for patients with type I and type II achalasia, whereas evidence suggests POEM is more effective in type III achalasia.

• #45 Role of botulinum toxin injection in treatment of achalasia – Heddle – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5438/html

  Achalasia is an uncommon disorder that can be found in children and adults of any age which typically presents with dysphagia, chest pain, and/or regurgitation of food. […] Idiopathic achalasia occurs due to a loss of the nitric oxide-releasing inhibitory nerves in the lower esophageal sphincter, which creates an imbalance between excitatory input added to intrinsic myotonic tone and inhibitory input. The concept behind botulinum toxin injection for achalasia is that it addresses this imbalance by blocking acetylcholine release from excitatory neurones acting on the lower esophageal sphincter. This results in a decrease in lower esophageal sphincter tone that can allow improved esophageal emptying. […] Current guidelines suggest a limited role for botulinum toxin injection into the lower esophageal sphincter, largely confined to older adults where other more definitive therapies are contraindicated because of co-morbidities.

• #46 Role of botulinum toxin injection in treatment of achalasia – Heddle – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5438/html

  The 2018 ISDE achalasia guidelines recommend that botulinum toxin injection for achalasia: (I) has little place in treatment of achalasia in those aged less than 50 years; (II) should mainly be used in those who are unfit for surgery or as a bridge to more definitive therapies such as surgery or balloon dilatation, and (III) repeat injections are safe but less effective than initial treatment. […] This study suggests that POEM may be the preferred modality for type 1 and 3 achalasia, and that results with type 2 achalasia are generally good (over 90% success with either laparoscopic Hellers myotomy or POEM) and reasonable results are seen with pneumatic dilatation (84% success). […] The literature supports the idea that botulinum toxin should be reserved for patients with achalasia who are not suitable for more definitive procedures such as laparoscopic cardiomyotomy, serial pneumatic dilatation of the lower esophageal sphincter, or peroral endoscopic esophageal myotomy (POEM).

• #47 Role of botulinum toxin injection in treatment of achalasia – Heddle – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5438/html

  Botulinum toxin retains a role in those individuals with poor life expectancy and perhaps those aged over 75 years, especially if they have significant comorbidities. Its advantages are that it is minimally invasive, it has a good safety profile, and it has good rate of initial success, particularly in those with type 2 achalasia.

• #48 Role of botulinum toxin injection in treatment of achalasia – Heddle – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5438/html

  The 2018 ISDE achalasia guidelines recommend that botulinum toxin injection for achalasia: (I) has little place in treatment of achalasia in those aged less than 50 years; (II) should mainly be used in those who are unfit for surgery or as a bridge to more definitive therapies such as surgery or balloon dilatation, and (III) repeat injections are safe but less effective than initial treatment. […] This study suggests that POEM may be the preferred modality for type 1 and 3 achalasia, and that results with type 2 achalasia are generally good (over 90% success with either laparoscopic Hellers myotomy or POEM) and reasonable results are seen with pneumatic dilatation (84% success). […] The literature supports the idea that botulinum toxin should be reserved for patients with achalasia who are not suitable for more definitive procedures such as laparoscopic cardiomyotomy, serial pneumatic dilatation of the lower esophageal sphincter, or peroral endoscopic esophageal myotomy (POEM).

• #49 Pathogenesis of achalasia cardia

  https://www.wjgnet.com/1007-9327/full/v18/i24/3050.htm

  Achalasia is caused by loss of inhibitory ganglion in the myenteric plexus in the esophagus. Gradual progression of neuronal degeneration is associated with progression of the disease from vigorous to classic achalasia. Though several studies have attempted to explore initiating agents that may cause the disease, the exact factors responsible for the degeneration of ganglion cells in the myenteric plexus are poorly understood. The disease is likely to be multi-factorial involving host genetic factors, autoimmunity, and environmental factors such as infections. More studies are needed to explore the exact cause of this enigmatic disease.

• #50 Pathogenesis of Achalasia

  https://www.helicojournal.org/journal/view.php?number=249

  Achalasia is a rare esophageal motility disorder characterized by loss of myenteric neurons leading to aperistalsis of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). […] Achalasia may be an autoimmune disease targeting esophageal myenteric neurons with cell-mediated and antibody-mediated attack to an unidentified antigen. […] Initial immunologic reactions can begin in genetically predisposed persons who had viral infection, such as herpes simplex virus 1. […] The type of immune response and the intensity of the cytotoxic T-cell attack can determine the clinical presentation of the disease. […] Patients with Chicago Classification type III achalasia may present with chronic inflammation in the absence of neuronal loss, whereas patients with Chicago Classification type I or II achalasia present with a predominantly cytotoxic immune response with progressive loss of myenteric neurons. […] Further well controlled researches which reveal the unknown facts of pathogenesis are needed.

• #51 Focus on Achalasia in the Omics Era

  https://www.mdpi.com/1422-0067/25/18/10148

  Achalasia is a rare and complex esophageal disease of unknown etiology characterized by difficulty in swallowing due to the lack of opening of the lower esophageal sphincter and the absence of esophageal peristalsis. […] Recent advancements in technology for analyzing DNA, RNA and biomolecules in high-throughput techniques are offering new opportunities to better understand the etiology and the pathogenetic mechanisms underlying achalasia. […] Achalasia is a heterogeneous condition with an etiology not fully understood. Autoimmune and inflammatory processes, possibly triggered by infectious agents, exposure to environmental factors, occurrence of familial achalasia, its association with well-defined genetic syndromes and a plethora of secondary causes, have been linked to the manifestation of the disease, and although there is a belief that genetic factors, along with their impacts on transcriptomics, microbiomics, viromics and proteomics may play a significant role, there is still a lack of concrete evidence.

• #52 Focus on Achalasia in the Omics Era

  https://www.mdpi.com/1422-0067/25/18/10148

  The most common form of achalasia is idiopathic (without a known or demonstrable cause) and mostly occurs sporadically, whereas in the minority of cases, it is a familial disorder that follows a dominant inheritance pattern. […] For this reason, genetics could be a valid tool to identify in advance at-risk patients who could benefit from targeted therapies and to prevent or slow the progression of the disease. […] The integration of various types of omics data, multi-omics and clinical data, enables the production of more detailed information and is commonly used to discover potential underlying changes that trigger diseases contributing to the understanding of the pathogenic mechanisms or to identify potential targets for treatments. […] The National Cancer Institute defined biomarkers as biological molecules in blood, bodily fluids, or tissues that reveal whether a process, condition, or disease is normal or aberrant.

• #53 Focus on Achalasia in the Omics Era

  https://www.mdpi.com/1422-0067/25/18/10148

  Despite great progress in this field, precise and definitive omics-based disease biomarkers have yet to be found for the majority of disorders, including inflammatory and neoplastic conditions. […] In this context, scientific evidence about the study of achalasia with an omics approach is scarce and only future studies will be able to elucidate new perspectives and open new avenues for the management of complex diseases like this. […] Achalasia is characterized by a loss of inhibitory ganglia and neurons in the esophageal neural plex. Although the cause of this neuronal degeneration is mainly unknown, immune cell- and antibody-mediated mechanisms seem to be involved, possibly triggered by infectious agents, in individuals with a genetic susceptibility. […] What emerges from this study of literature review on achalasia omics is that the field of genomics has allowed the identification of rare genetic variants and polymorphisms in likely candidates genes encoding for proteins involved in the immune response.

• #54 Focus on Achalasia in the Omics Era

  https://www.mdpi.com/1422-0067/25/18/10148

  Despite great progress in this field, precise and definitive omics-based disease biomarkers have yet to be found for the majority of disorders, including inflammatory and neoplastic conditions. […] In this context, scientific evidence about the study of achalasia with an omics approach is scarce and only future studies will be able to elucidate new perspectives and open new avenues for the management of complex diseases like this. […] Achalasia is characterized by a loss of inhibitory ganglia and neurons in the esophageal neural plex. Although the cause of this neuronal degeneration is mainly unknown, immune cell- and antibody-mediated mechanisms seem to be involved, possibly triggered by infectious agents, in individuals with a genetic susceptibility. […] What emerges from this study of literature review on achalasia omics is that the field of genomics has allowed the identification of rare genetic variants and polymorphisms in likely candidates genes encoding for proteins involved in the immune response.

• #55 Focus on Achalasia in the Omics Era

  https://www.mdpi.com/1422-0067/25/18/10148

  Deranged esophageal peristalsis and loss of LES function, due to imbalance between excitatory neurons releasing acetylcholine and inhibitory neurons that release NO and VIP, are the abnormalities and diagnostic characteristics of achalasia. […] Thus, polymorphisms in NOS, VIP and c-kit genes represented ideal candidates to explain the inflammation and the inhibitory neurotransmission observed in achalasia.

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