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Achalasia

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Achalasia is a rare motor disorder of the oesophagus, characterised by the absence of peristalsis and impaired swallow-induced relaxation. These motor abnormalities result in stasis of ingested food in the oesophagus, leading to clinical symptoms, such as dysphagia, regurgitation of food, retrosternal pain and weight loss. Although it is well demonstrated that loss of myenteric oesophageal neurons is the underlying problem, it still remains unclear why these neurons are preferentially attacked and destroyed by the immune system. This limited insight into pathophysiology explains the fact that treatment is limited to interventions aimed at reducing the pressure of the lower oesophageal sphincter. The most successful therapies are clearly pneumatic dilatation and Heller myotomy with short-term success rates of 70–90%, declining to 50–65% after more than 15 years. The challenge for the coming years will undoubtedly be to get more insight into the underlying disease mechanisms and to develop a treatment to restore function.

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

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