Esophageal motility disorders & Achalasia Division of Gastroenterology Department of Internal Medicine R4 Woo Yong Sik/Prof. Jang Jae young

Normal physiology of esophagus

Normal eosphageal manometer and fluroscopy of barium swallow

Examples of esophageal peristalsis and LES relaxation during three swallows each of 5 mL of water.

Classification of esophageal motility abnormalities Inadequate LES relaxation Classic achalasia Atypical disorders of LES relaxation Uncoordinated contraction Diffuse esophageal spasm Hypercontraction Nutcracker esophagus Isolated hypertensive LES Hypocontraction Ineffective esophageal motility Gut 2001;49:145–151

Motility patterns in esophageal smooth muscle disorders Motility patterns in esophageal smooth muscle disorders. Harrison's Principles of Internal Medicine. 16th ed 1739–1745.

Esophageal manometric findings in classic achalasia and vigorous achalasia

Esophageal manometric findings in diffuse esophageal spasm.

Esophageal manometric findings in Nutcracker esophagus

Esophageal manometric findings in systemic sclerosis.

Achalasia

Introduction Sir Thomas Willis, first described in 1674 who described a man in good health who vomited ‘whatever eaten’ treated with whale bone rod with small piece of sponge on its end inserted into esophagus to relieve obstruction ‘achalasia of the cardia’ by Hurst in 20th century term achalasia comes from Greek for failure to relax

normal condition : excitatory, Ach motor neurons inhibitory, NO motor neurons Achalasia : resulting from loss of inhibitory neurons results in elevation in basal LESP and absence of relaxation of LES Achalasia with complete loss of myenteric neurons. basal LESP is below normal owing to absent excitatory neurons,

Pathophysiology neurodegenerative insult secondary achalasia inflammatory origin with possibly (slow) viral involvement. genetic, autoimmune or infectious origin of the neural damage, secondary achalasia associated with Chagas disease caused by trypanozoma cruzi endemic to Southern America

Important causes of achalasia

Clinical feature Achalasia is a rare disease affecting both genders annual incidence between 0.5~1/100.000 per yr incidence peaks in the 3rd and 7th life decade chest pain is reported by 1/3~1/2 of pt with achalsia wt. loss is common, confused with eating disorder combination of dysphagia for both “solid and liquids” suggesting achalasia over mechanical obstruction “symptoms rather than physical finding are hallmark”

Diagnosis typically delayed 2-3 yrs from onset of symptoms suspected from carefully obtained history duration correlation with esophageal diameter

Endoscopy Retention of undigested food in esophagus regarded as a more specific parameter in diagnosing achalasia only in pt with advanced disease and severe transit impairment Candida esophagitis in immune competent pt

Radiographic studies Typical radiographic findings smooth tapering in the distal esophagus with “bird´s beak” or “champagne glass” appearance lack of primary peristalsis noticed during fluoroscopy formation of a contrast column above LES none be present in early phase of disease normal barium esophagogram not rule out achalasia

Conventional barium esophagogram in achalasia Bird’s beak Conventional barium esophagogram in achalasia

“Timed barium” swallow in achalasia. Images were 1, 3 and 5 min after ingestion of 50-100ml barium. monitor patients after therapy in order to detect recurring disease before becoming clinically overt. Before (A), after (B) treatment.

Esophageal manometry “gold standard” in diagnosing calssic achalasia three characteristic manometric features elevated resting LES pr (above 45 mmHg) incomplete LES relaxation after swallow aperistalsis in smooth muscle portion of esophageal body Vigorous achalasia simultaneous esophageal contractions amplitudes >60 mmHg prognostic & therapeutic value of this separation controversial

Esophageal manometric findings in classic achalasia and vigorous achalasia

Treatment of achalasia goal in management of achalasia early diagnosis and treatment before reaching this end-stage phase when esophagectomy becomes inevitable restoring neurons of myenteric plexi Not available currently aim at facilitating bolus transit across LES Phamacologic treatment Botulinum toxin injections Pneumatic balloon dilatation Surgical lower esophageal myotomy

Oral pharmacologic treatment smooth muscle relaxants CCB, nitrates and phosophodiestarase inhibitors aimed at reducing LES pr. clinically available pharmacologic therapies limited value in treatment of achalasia. Indication pts not willing or unable to undergo any other procedure pts waiting for more definitive therapy supportive treatment for refractory chest pain in achalasia.

Botulinum toxin injections Pasricha et al reported on use of botulinum toxin A (Botox) injections in LES to treat achalasia. NEJM 1995;332:774-778. original protocol, 80~100IU of BoTox are injected in 4 quadrants just above Z-line, an area LES Initial beneficial effect occurs in 60~75% duration of BoTox treatment varies according to various studies , generally on average 6-12 mo.

Mechanism of Action of Botulinum Toxin A, Release of acetylcholine at the neuromuscular junction is mediated by the assembly of a synaptic fusion complex that allows the membrane of the synaptic vesicle containing acetylcholine to fuse with the neuronal cell membrane. The synaptic fusion complex is a set of SNARE proteins, which include synaptobrevin, SNAP-25, and syntaxin. After membrane fusion, acetylcholine is released into the synaptic cleft and then bound by receptors on the muscle cell. B, Botulinum toxin binds to the neuronal cell membrane at the nerve terminus and enters the neuron by endocytosis. The light chain of botulinum toxin cleaves specific sites on the SNARE proteins, preventing complete assembly of the synaptic fusion complex and thereby blocking acetylcholine release. Botulinum toxins types B, D, F, and G cleave synaptobrevin; types A, C, and E cleave SNAP-25; and type C cleaves syntaxin. Without acetylcholine release, the muscle is unable to contract. SNARE indicates soluble NSF-attachment protein receptor; NSF, N-ethylmaleimide-sensitive fusion protein; and SNAP-25, synaptosomal-associated protein of 25 kd. JAMA 2001;285;1059~1070

Dilatation oldest treatment modality and first described > 300 yrs ago with a tool of time – whale fishbone Pneumatic dilators are conventionally used no clear consensus on technical details of balloon dilatation trend to begin with smaller diameter (3cm in adult) dilator increase diameter in graded fashion subsequently Good response was reported 60~95% Symptomatic outcome depends on reduction LES pr. and emptying unlike phamacologic treatment and BoTox

Efficacy reduced by half for subsequent dilatation poor initial result or rapid recurrence lesser response Morbidity in 3% of patients, Mortality rarely reported most related to esophageal perforation, Perforation more likely in severe malnurished pt. Disadvantages - lesser short- and long-term efficacy in comparison with myotomy, particlularly in young patients

Esophagomyotomy Goal of surgical theraphy to reduce LES resting pr without completely compromising reflux Ernst Heller first described in 1914 two-cardiomyotomy technique (one ant. and one post.) along GEJ Modification of this procedure (Heller myotomy and Toupet posterior fundoplication)

Esophagomyotomy Good results from open myotomy occur in 80~90% reduces LED pr. more than pneumatic dilatation accounting for greater efficacy Minimally invasive approaches to myotomy as effective as open counterpart surgical procedure of choice as limited long-term data

Comparison of Primary Treatments for Idiopathic Achalasia

Complication related to retention and stasis in esophagus esophagitis, up to 30% nocturnal coughing Prevelence of carcinoma is higher in achalasia rate of ranging from 2~7% in larger case series 50 times in general population Squamous hyperplasia, apperance of p53 mutation in response to chronic stasis