3Achalasia
Section snippets
The lower oesophageal sphincter and swallow-induced relaxation
The junction between the oesophagus and the stomach is a specialised region, composed of the LOS and its adjacent anatomic structures, the gastric sling and the crural diaphragm.2 Together these structures aim to prevent reflux of gastric contents across the oesophagogastric junction (OGJ) into the oesophagus. However, with each swallow, the LOS has to relax to allow passage of ingested food into the stomach. Swallow-induced relaxation is part of primary peristalsis, a complex reflex generated
Loss of inhibitory innervation in achalasia
As described above, the LOS pressure decreases upon swallowing in order to allow passage of the ingested food to the stomach. In patients with achalasia, however, manometry typically shows an incomplete relaxation of the LOS upon deglutition.*19, 20 In addition, oesophageal peristalsis is absent and resting tone of the LOS will often be elevated. The loss of the nitrergic neurons results in the absence of relaxation of the LOS in response to various stimuli both in vitro and in vivo. Muscle
Epidemiology and diagnosis
Achalasia is a rare disorder with an estimated prevalence of 0.5–1 per 100 000 per year without a clear age predilection.20 In children, it is part of the Triple A syndrome, characterised by achalasia, alacrima and adrenocorticotrophic hormone resistant adrenal insufficiency, and has been suggested to be part of Alport's syndrome in some patients. Recent observations also suggest that achalasia is more frequent in Down's syndrome,39 and may even be related to previous trauma.40 In a
Treatment
The treatment of achalasia is aimed at improving bolus transport across the LOS by reducing the pressure at the LOS. At present, treatment options in achalasia are pharmacotherapy, pneumatic dilatation, surgery or injection of botulinum toxin. For a detailed overview, the reader is referred to excellent reviews on this matter.51, 52
Increased risk of oesophageal carcinoma?
In the Amsterdam cohort of patients,60 32 of the 249 patients had deceased, 6 (19%) of them died of oesophageal carcinoma. Three had a squamous cell carcinoma, two had an adenocarcinoma while the cause of cancer was unknown in the remaining patients. Similar data were reported previously83 confirming that achalasia is a risk factor for oesophageal carcinoma. Earlier reports have indeed indicated that the incidence of oesophageal carcinoma in achalasia patients is up to 33 times higher83, 84, 85
Summary
Although achalasia is a well defined and intensely studied disorder, the insight into the underlying pathogenesis is still very limited. Moreover, although the ultimate goal of treatment should be restoration of oesophageal peristalsis and LOS relaxation, gastroenterologists and surgeons continue to destroy the LOS. Heller myotomy and pneumatic dilatation are successful in 70–90% of patients in the first years, but the success rate slowly declines with time. Which of these treatments is the
References (89)
- et al.
Central mechanisms of lower esophageal sphincter control
Gastroenterol Clin North Am
(2002) - et al.
Neuronal pathways and transmission to the lower esophageal sphincter of the guinea pig
Gastroenterology
(1998) - et al.
Lower esophageal sphincter is achalasic in nNOS(−/−) and hypotensive in W/W(v) mutant mice
Gastroenterology
(2001) - et al.
Role of nitric oxide in lower esophageal sphincter relaxation to swallowing
Life Sci
(1992) - et al.
Characterization and mediation of inhibitory junction potentials from opossum lower esophageal sphincter
Gastroenterology
(1993) - et al.
The effects of recombinant human hemoglobin on esophageal motor functions in humans
Gastroenterology
(1995) - et al.
Manometric heterogeneity in patients with idiopathic achalasia
Gastroenterology
(2001) Oesophageal motility disorders
Lancet
(2001)- et al.
Clinical relevance of nitric oxide in the gut
Lancet
(1994) - et al.
Paradoxical lower esophageal sphincter contraction induced by cholecystokinin-octapeptide in patients with achalasia
Gastroenterology
(1981)
Histopathologic features in esophagomyotomy specimens from patients with achalasia
Gastroenterology
Esophageal achalasia: is the herpes simplex virus really innocent?
J Gastrointest Surg
Achalasia and Down's syndrome: coincidental association or something else?
Am J Gastroenterol
Clinical presentations and complications of achalasia
Gastrointest Endosc Clin N Am
Botulinum toxin for spastic gastrointestinal disorders
Baillieres Best Pract Res Clin Gastroenterol
Long term results of pneumatic dilation in achalasia followed for more than 5 years
Am J Gastroenterol
The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia
Clin Gastroenterol Hepatol
Predictors of outcome of pneumatic dilation in achalasia
Clin Gastroenterol Hepatol
Achalasia: current evaluation and therapy
Ann Thorac Surg
Risk factors for immediate complications after progressive pneumatic dilation for achalasia
Am J Gastroenterol
Esophageal achalasia: laparoscopic versus conventional open Heller–Dor operation
Am J Surg
Treatment of esophageal achalasia with laparoscopic Heller myotomy and Dor partial anterior fundoplication: prospective evaluation of 100 consecutive patients
J Gastrointest Surg
Long-term outcome of laparoscopic Heller–Dor surgery for esophageal achalasia: possible detrimental role of previous endoscopic treatment
J Gastrointest Surg
A prospective randomized study comparing forceful dilatation and esophagomyotomy in patients with achalasia of the esophagus
Gastroenterology
Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract
Gastroenterology
Achalasia and squamous cell carcinoma of the esophagus: analysis of 241 patients
Ann Thorac Surg
Achalasia-associated squamous cell carcinoma of the esophagus: flow-cytometric and histological evaluation
Gastroenterology
Treatment of achalasia with pneumatic dilatations
Gut
The esophagogastric junction
N Engl J Med
Brain stem control of swallowing: neuronal network and cellular mechanisms
Physiol Rev
Neural circuits in swallowing and abdominal vagal afferent-mediated lower esophageal sphincter relaxation
Am J Med
Swallowing reflex and brain stem neurons activated by superior laryngeal nerve stimulation in the mouse
Am J Physiol Gastrointest Liver Physiol
The role of nitric oxide in inhibitory non-adrenergic non-cholinergic neurotransmission in the canine lower oesophageal sphincter
Br J Pharmacol
Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter
Am J Physiol
Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions
Neurogastroenterol Motil
Biphasic relaxation of the opossum lower esophageal sphincter: roles of NO, VIP, and CGRP
Am J Physiol
Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter
Dig Dis Sci
The role of the l-arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter
Acta Physiol Scand
Effect of l-NMMA on postprandial transient lower esophageal sphincter relaxations in healthy volunteers
Dig Dis Sci
Effects of postganglionic nerve stimulation in oesophageal achalasia: an in vitro study
Gut
Esophageal and lower esophageal sphincter response to balloon distention in patients with achalasia
Dig Dis Sci
Failure of transient lower oesophageal sphincter relaxation in response to gastric distension in patients with achalasia: evidence for neural mediation of transient lower oesophageal sphincter relaxations
Gut
Etiology and pathogenesis of achalasia
Gastrointest Endosc Clin N Am
Patients with achalasia lack nitric oxide synthase in the gastro-oesophageal junction
Eur J Clin Invest
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Childhood esophageal achalasia: Case report from Afghanistan with literature review
2022, International Journal of Surgery Case ReportsCitation Excerpt :Gastroscopy may show residual food, mucosal changes due to chronic irritation and finding of tight LES which doesn't open by air insufflation [9]. Manometry remains the gold standard for the diagnosis of achalasia with up to 90% efficacy [19,20]. It allows us to differentiate achalasia types according to Chicago classification [14,21].
High-Resolution Esophageal Manometry: Techniques and Use in the Diagnosis of Esophageal Motility Disorders and for Surgical Decision Making
2019, Shackelford's Surgery of the Alimentary Tract: 2 Volume SetClinical factors and high-resolution manometry predicting response to surgery for achalasia in children
2018, Journal of Surgical ResearchCitation Excerpt :At this time, there is little indication for pharmacologic intervention (e.g., nitrates, erythromycin, tricyclic antidepressants, and calcium channel blockers). These often lead to unpredictable results and side effects.8,29 Procedural treatment options include intrasphincteric botulinum toxin injection and endoscopic pneumatic dilation of the LES.6,7
Clinical and Translational Aspects of Normal and Abnormal Motility in the Esophagus, Small Intestine and Colon
2018, Physiology of the Gastrointestinal Tract, Sixth EditionPrimary Achalasia: Practice Implications
2016, Journal for Nurse PractitionersCitation Excerpt :However, the effects wear off after 1 to 3 months, and injections can only be given every 6 to 12 months.19 Boeckxstaens9 reported fewer relapses when the initial Botox injection is followed by a second injection 1 month later. Reynoso et al21 reported Botox therapy to be associated with very high symptomatic relapse after 2 years.
Surgical intervention for esophageal dysmotility
2015, Techniques in Gastrointestinal Endoscopy