Achalasia

• Achalasia is a primary oesophageal motility disorder characterised by the progressive degeneration of inhibitory nitrinergic neurons in the myenteric plexus. This neuronal loss disrupts peristalsis and impairs lower oesophageal sphincter (LES) relaxation, leading to functional obstruction at the gastro-oesophageal junction. 
• While the precise cause remains unknown, several contributing factors have been proposed, including infectious, autoimmune, and genetic mechanisms.
  
  

Infectious Triggers

• Chagas Disease
  • Trypanosoma cruzi infection leads to neuronal destruction in the oesophageal wall, resulting in a motility disorder that mimics achalasia. This form of secondary achalasia is commonly reported in regions where Chagas disease is endemic.

• Viral Infections
  • Herpes simplex virus type 1 (HSV-1) and measles virus have been implicated as potential triggers, with increased antibody titres detected in affected individuals.
  • T-cell reactivity to HSV-1 antigens has been observed within the myenteric plexus, suggesting a viral-driven autoimmune response.
    
    

Autoimmune Mechanisms

• Myenteric Plexus Antibodies
  • A significant proportion of patients exhibit circulating autoantibodies targeting enteric neurons, supporting an immune-mediated pathogenesis.

• T-cell Mediated Inflammation
  • Histological examination frequently reveals T-cell infiltration in the myenteric plexus, contributing to neuronal loss.

• HLA Associations
  • Certain human leukocyte antigen (HLA) class II alleles have been linked to an increased susceptibility, with strong associations found in European studies.
  • Similar genetic markers have been implicated in other autoimmune disorders, suggesting a shared immunopathogenic mechanism.
    
    

Genetic Factors

• Familial Achalasia
  • Although rare, familial clustering has been reported, particularly in cases with a history of consanguinity.

• Triple A (Allgrove) Syndrome
  • This autosomal recessive disorder, featuring achalasia, alacrima, and adrenal insufficiency, has been mapped to mutations on chromosome 12.

• Single Nucleotide Polymorphisms (SNPs)
  • The rs1799724 SNP, positioned between the lymphotoxin-alpha (LTA) and tumour necrosis factor-alpha (TNFα) genes, has been linked to increased disease risk.
  • A genome-wide association study identified multiple SNPs in the major histocompatibility complex region of chromosome 6, a locus associated with various autoimmune conditions.
    
    

Neurophysiological Basis

• The smooth muscle of the distal oesophagus and LES is controlled by vagal pre-ganglionic fibres originating in the dorsal motor nucleus. These fibres synapse in the myenteric plexus with post-ganglionic neurons, which regulate motor function.
• Two key types of neurons are involved:
  • Excitatory cholinergic neurons that release acetylcholine and substance P, promoting muscle contraction.
  • Inhibitory nitrinergic neurons that release nitric oxide (NO) and vasoactive intestinal peptide (VIP), facilitating muscle relaxation.
    
    

Neuronal Degeneration and Functional Impairment

• The loss of inhibitory neurons leads to persistent LES contraction and the absence of coordinated peristalsis.
• Histopathological studies show a reduction in myenteric ganglion cells, often with an associated inflammatory response involving lymphocytes, eosinophils, and mast cells.
• The selective loss of NO-producing neurons eliminates the normal latency gradient required for sequential contractions along the oesophageal body, resulting in either simultaneous contractions or complete aperistalsis.
  
  

Inflammatory and Autoimmune Contributions

• The presence of T-cell infiltration and fibrosis in the myenteric plexus suggests an immune-mediated mechanism.
• Some patients exhibit circulating antibodies targeting enteric neurons, further supporting an autoimmune role in the disease process.
• Genetic associations, particularly with certain human leukocyte antigen (HLA) class II variants, suggest an immunogenetic predisposition.
• Viral infections, including herpes simplex virus type 1 (HSV-1) and measles virus, have been proposed as potential triggers for immune-mediated neuronal destruction, although direct causation remains uncertain.
  
  

Oesophageal Dysfunction and Structural Changes

• Loss of Peristalsis and Oesophageal Dilatation
  • The absence of effective peristalsis results in oesophageal stasis and retention of food.
  • Chronic obstruction at the gastro-oesophageal junction leads to progressive oesophageal dilatation, which contributes to further motility impairment.

• Upper Oesophageal Sphincter (UES) Dysfunction
  • Some patients exhibit impaired UES relaxation, leading to difficulty in venting swallowed air.
  • Experimental studies show that oesophageal air insufflation often triggers a paradoxical increase in UES pressure rather than relaxation, contributing to symptoms such as chest discomfort and bloating.

• Post-Treatment Oesophageal Adaptations
  • Following therapeutic interventions aimed at reducing LES pressure, such as pneumatic dilation or myotomy, residual contractile activity may be observed.
  • Imaging studies assessing oesophageal distensibility post-intervention indicate partial restoration of function in some patients.
    
    

Incidence and Prevalence

• The estimated annual incidence of achalasia ranges from 1.6 to 2.92 per 100,000 persons in North America, with similar rates reported in some European populations.
• In South Australia, the incidence is estimated at 2.3 to 2.8 per 100,000 persons per year.
• Lower incidence rates are observed in some Asian and African populations:
  • Korea: 0.39 per 100,000 persons per year
  • Zimbabwe: 0.03 per 100,000 persons per year
  • Singapore: 0.3 per 100,000 persons per year
• The prevalence of achalasia varies widely, with estimates ranging from 8.0 to 27.1 per 100,000 persons.
• Some studies indicate an increasing incidence over time, particularly in Western countries. This trend may be due to better disease recognition, improved diagnostic techniques, and broader access to high-resolution manometry.
  
  
  

Age and Sex Distribution

• Achalasia can occur at any age, though it is most frequently diagnosed between 25 and 60 years.
• The median age at diagnosis is 53 years.
• The condition affects males and females equally, with a 1:1 ratio.
• Childhood achalasia is rare, accounting for less than 5% of cases.
  
  

Geographic and Ethnic Variability

• Significant regional and racial differences in achalasia incidence have been observed:
  • In New Zealand, Pacific Islanders and Māori have a higher incidence compared to the white population.
  • In Singapore, achalasia is more common in Chinese and Indian populations than in Malays.
  • In the United States, incidence appears similar across racial groups.
• The variation in achalasia incidence between populations suggests an interaction of genetic susceptibility and environmental influences.
  
  
  

Associations with Other Conditions

• Spinal Cord Injury (SCI): Oesophageal motility abnormalities resembling achalasia have been observed in up to 12% of paraplegic and 4% of tetraplegic patients.
• Eating Disorders: Achalasia-like motility dysfunction has been reported in patients with anorexia nervosa.
• Post-Sclerotherapy Changes: Endoscopic sclerotherapy for oesophageal varices has been associated with oesophageal dysmotility, including defective lower oesophageal sphincter function.
• Paediatric Achalasia: A study in the Netherlands reported an annual incidence of 0.1 per 100,000 persons in children.
  
  

Trends in Treatment Utilisation

• The use of Heller myotomy for achalasia has increased over time, with a shift from open surgery to laparoscopic techniques.
• This trend is likely due to higher disease recognition, as well as advancements in minimally invasive surgical approaches that improve patient outcomes.
  
  

Key Diagnostic Features

• Dysphagia (Most Common Symptom)
  • Affects both solids and liquids, which helps distinguish it from structural causes of oesophageal obstruction, where dysphagia to liquids is uncommon unless the disease is advanced.
  • Progressive in nature, often prompting patients to modify their eating habits, such as increasing fluid intake or taking smaller bites.

• Regurgitation
  • Typically occurs due to retention of undigested food and saliva in the oesophagus.
  • More pronounced when lying down, leading to nocturnal regurgitation and aspiration risk.
  • Unlike GERD, the regurgitate is bland rather than acidic.

• Retrosternal Pressure and Pain
  • Can be provoked by swallowing liquids but is sometimes relieved by continued drinking.
  • More commonly reported in younger individuals, with descriptions of a cramping or squeezing sensation.
  • May persist despite successful treatment such as dilation.

• Posturing to Aid Swallowing
  • Patients often develop compensatory behaviours to facilitate oesophageal emptying, including:
    • Arching the neck and shoulders.
    • Raising the arms.
    • Walking around after meals.

• Weight Loss
  • Usually mild and occurs gradually.
  • Rapid weight loss should prompt evaluation for pseudoachalasia, particularly malignancy-related causes.
    
    

Other Associated Symptoms

• Heartburn
  • More likely due to fermentation of retained food rather than reflux of gastric acid.
  • Can lead to misdiagnosis as GERD.

• Slow Eating and Prolonged Meal Times
  • Patients unconsciously adapt to dysphagia by eating slowly, chewing thoroughly, and drinking more fluids.

• Coughing or Choking When Recumbent
  • Occurs due to regurgitation of oesophageal contents.
  • Can lead to aspiration pneumonia, particularly in advanced cases.

• Globus Sensation
  • Some patients report a persistent feeling of a lump in the throat.

• Hiccups
  • Related to oesophageal retention of food and possible diaphragmatic irritation.
    
    

Risk Factors

• Triple A (Allgrove) Syndrome
  • A rare genetic disorder presenting with achalasia, alacrima, and adrenal insufficiency.

• Viral Associations
  • Increased antibody titres against herpes simplex virus (HSV-1) and measles virus have been detected in some patients, though causation remains unproven.

• Autoimmune Factors
  • Presence of antibodies against the myenteric plexus in some individuals supports an immune-mediated mechanism.

• Genetic Susceptibility
  • HLA class II antigens have been identified more frequently in patients with achalasia.
  • Familial achalasia is rare but has been observed, particularly in cases with consanguineous parentage.
    
    

Weight Loss

• Often mild and gradual, resulting from prolonged difficulty in swallowing.
• Rapid and significant weight loss should raise suspicion of pseudoachalasia, particularly malignancy-related causes.
• Posturing to Aid Swallowing
  • Patients may adopt compensatory positions to assist with oesophageal emptying, including:
    • Arching the neck and shoulders.
    • Raising the arms.
    • Walking around after meals.

Regurgitation and Its Consequences

• Retained food and liquids in the oesophagus lead to regurgitation, particularly in later stages of the disease.
  • Unlike gastro-oesophageal reflux, the regurgitated material is typically bland rather than acidic.
  • Nocturnal regurgitation may result in aspiration pneumonia.
• Coughing and Choking Episodes
  • Can occur due to aspiration of retained oesophageal contents, especially when recumbent.
  • Frequent aspiration may lead to recurrent chest infections or a persistent chronic cough.
• Heartburn
  • More commonly due to fermentation of retained food rather than acid reflux.
  • Often mistaken for gastro-oesophageal reflux disease (GERD), leading to misdiagnosis.
• Globus Sensation (Lump in the Throat)
  • Some patients report a sensation of a lump in the throat, unrelated to actual obstruction.
• Hiccups
  • May be triggered by prolonged oesophageal retention of food and subsequent irritation of the diaphragm.
• Oesophageal Dilatation and Its Effects
  • Chronic oesophageal outflow obstruction may lead to progressive oesophageal dilatation.
  • Advanced cases show structural remodelling of the oesophageal wall, contributing to impaired peristaltic clearance.
• Upper Oesophageal Sphincter Dysfunction
  • Some patients exhibit difficulty belching due to impaired relaxation of the upper oesophageal sphincter.
  • Studies indicate that oesophageal air insufflation in these patients may paradoxically increase upper oesophageal sphincter pressure rather than induce relaxation.
    
    

First-Line Investigations

• Essential for excluding malignancy, particularly pseudoachalasia.
• Early-stage achalasia may have normal findings.
• Advanced cases may show:
  • Dilated oesophagus with retained food and saliva.
  • Mucosal changes with a frothy appearance due to stasis.
  • Tight gastro-oesophageal junction, which typically opens with gentle pressure.
• Biopsies from the cardia should be obtained to rule out malignancy.
  
  

• Frequently used as an initial imaging test.
• Findings vary depending on disease stage:
  • Early achalasia: May appear normal.
  • Advanced achalasia:
    • Dilated oesophagus with retained contrast.
    • Loss of peristalsis and delayed oesophageal emptying.
    • "Bird-beak" narrowing at the gastro-oesophageal junction.
    • In severe cases, a tortuous, sigmoid-shaped oesophagus.
      
      

• Detects incomplete relaxation of the lower oesophageal sphincter (LES) and absent peristalsis.
• Chicago Classification subtypes:
  • Type I (Classic Achalasia): Complete aperistalsis with no oesophageal pressurisation.
  • Type II: Pan-oesophageal pressurisation in ≥20% of swallows.
  • Type III (Spastic Achalasia): Premature distal oesophageal contractions in ≥20% of swallows.
    
    

Additional Investigations

• Low sensitivity but may suggest achalasia.
• Findings include:
  • Dilated oesophagus with air-fluid level.
  • Absence of gastric gas bubble.
    
    

• Used to differentiate achalasia from malignancy.
• Can detect:
  • Oesophageal wall thickening, which may indicate pseudoachalasia.
  • Dilatation of the oesophagus in longstanding cases.
• Recommended in older patients or those with rapid or significant weight loss.
  
  

• A series of radiographs taken at preset intervals after barium ingestion.
• Measures oesophageal emptying over time.
• Useful for monitoring treatment response and disease progression.
  
  

• Assesses delayed oesophageal transit.
• Less commonly used but helpful for treatment monitoring.
  
  

• Measures oesophageal distensibility and sphincter function.
• Used in cases where manometry results are inconclusive.
• Provides real-time assessment during endoscopy or surgery.
  
  

Primary Differential Diagnoses

• Signs and Symptoms:
  • Progressive dysphagia, initially for solids, later for liquids in advanced cases.
  • Significant weight loss.
• Investigations:
  • Barium swallow and endoscopy: Demonstrates tumour-related oesophageal obstruction.
  • Biopsy: Confirms malignancy.
  • CT scan: Assesses tumour invasion and metastasis.
    
    

• Cause:
  • Achalasia-like motility dysfunction secondary to malignancy, paraneoplastic syndromes, or post-surgical changes.
• Signs and Symptoms:
  • Rapid onset of dysphagia with greater weight loss and shorter symptom duration compared to idiopathic achalasia.
• Investigations:
  • Manometry: Findings indistinguishable from idiopathic achalasia.
  • Endoscopic ultrasound and biopsy: Essential to rule out malignancy.
    
    

Oesophageal Motility Disorders

• Signs and Symptoms:
  • Chest pain often more prominent than dysphagia.
  • Dysphagia is intermittent rather than progressive.
• Investigations:
  • Manometry: High-amplitude, uncoordinated contractions instead of aperistalsis.
  • Barium swallow: May reveal a “corkscrew” or “rosary bead” oesophagus.
    
    

• Signs and Symptoms:
  • Dysphagia due to inflammatory swelling or fibrotic peptic stricture.
  • Associated symptoms include heartburn and acid regurgitation.
• Investigations:
  • Endoscopy: May show oesophagitis or strictures.
  • Barium swallow: Demonstrates strictures or hiatus hernia.
  • pH monitoring: Confirms pathological reflux.
    
    

• Signs and Symptoms:
  • Dysphagia and food bolus impaction, frequently in younger patients with a history of atopy.
• Investigations:
  • Endoscopy: May show a ringed oesophagus with furrows and white spots.
  • Oesophageal biopsy: Eosinophilic infiltration (>15 eosinophils per high-power field).
    
    

Neuromuscular and Systemic Disorders

• Signs and Symptoms:
  • Raynaud’s phenomenon, joint pain, and skin thickening.
• Investigations:
  • Serology: Antinuclear antibodies, rheumatoid factor, and creatine kinase.
  • Manometry: Low-amplitude contractions with ineffective oesophageal motility.
    
    

• Cause:
  • Trypanosoma cruzi infection leading to progressive oesophageal denervation.
• Signs and Symptoms:
  • Endemic to Latin America, often with associated cardiac and colonic involvement.
• Investigations:
  • Microscopy and PCR: Detect Trypanosoma cruzi in blood samples.
    
    

Endoscopic and Surgical Interventions

• First-line option for patients who are surgical candidates.
• Performed under sedation using air-inflated balloons to stretch and partially disrupt LES muscle fibres.
• Graded dilatation approach (30 mm followed by 35 mm or 40 mm if needed) has shown higher efficacy and safety.
• Remission rates:
  • 81% at 6 months, 77% at 12 months after a 30 mm balloon.
  • 40% at 5 years and 36% at 10–15 years after a single dilatation.
  • Success rates improve with repeated dilatations.
• Complications:
  • Perforation risk: 1% with a 30 mm balloon, higher with larger balloons or initial 35 mm dilatation.
  • Risk is increased in patients with oesophageal diverticula, prior surgery, or a dilated/tortuous oesophagus.
    
    

• 
  Preferred over dilatation for patients with type I and II achalasia.
• Involves surgical division of the LES muscle fibres to relieve obstruction.
• Fundoplication is performed concurrently to reduce post-operative gastro-oesophageal reflux.
• Outcomes:
  • Remission rates >75% at 5–10 years.
  • Superior symptom control compared to pneumatic dilatation for type II achalasia.
• Complications:
  • Postoperative acid reflux is common, requiring proton pump inhibitors (PPIs).
  • Perforation risk is <10%.
    
    

• Minimally invasive endoscopic procedure that enables precise myotomy.
• Most effective for type III achalasia, where spastic contractions extend beyond the LES.
• Success rates:
  • 92% at 2 years, superior to pneumatic dilatation.
  • More effective than Heller myotomy in long-term dysphagia control.
• Disadvantages:
  • Higher risk of reflux oesophagitis (41%) compared to surgical myotomy.
  • Requires expertise and high-volume centres for optimal outcomes.
    
    

Non-Surgical Management

• First-line for poor surgical candidates (frail, elderly, or those with severe comorbidities).
• Blocks acetylcholine release, lowering LES pressure and improving emptying.
• Efficacy:
  • Initial response >80%, but effects wane over time.
  • 68–75% symptom control at 2 years with repeat injections.
  • Long-term use may lead to antibody formation, reducing effectiveness.
    
    

• Used for temporary symptom relief while awaiting definitive treatment.
• Calcium channel blockers (e.g., nifedipine, verapamil) and nitrates (e.g., isosorbide dinitrate) relax the LES.
• Effectiveness:
  • Short-lived symptomatic relief.
  • Tolerance develops with chronic use, reducing long-term efficacy.
• Side effects: Hypotension, dizziness, headache.
  
  

• Gastrostomy for enteral feeding may be required in patients with severe dysphagia and malnutrition.
• Oesophagectomy is an option for patients with severely dilated (sigmoid) oesophagus or refractory disease despite repeated interventions.
  
  

Endoscopic and Surgical Interventions

• First-line option for patients who are surgical candidates.
• Performed under sedation using air-inflated balloons to stretch and partially disrupt LES muscle fibres.
• Graded dilatation approach (30 mm followed by 35 mm or 40 mm if needed) has shown higher efficacy and safety.
• Remission rates:
  • 81% at 6 months, 77% at 12 months after a 30 mm balloon.
  • 40% at 5 years and 36% at 10–15 years after a single dilatation.
  • Success rates improve with repeated dilatations.
• Complications:
  • Perforation risk: 1% with a 30 mm balloon, higher with larger balloons or initial 35 mm dilatation.
  • Risk is increased in patients with oesophageal diverticula, prior surgery, or a dilated/tortuous oesophagus.
    
    

• Preferred over dilatation for patients with type I and II achalasia.
• Involves surgical division of the LES muscle fibres to relieve obstruction.
• Fundoplication is performed concurrently to reduce post-operative gastro-oesophageal reflux.
• Outcomes:
  • Remission rates >75% at 5–10 years.
  • Superior symptom control compared to pneumatic dilatation for type II achalasia.
• Complications:
  • Postoperative acid reflux is common, requiring proton pump inhibitors (PPIs).
  • Perforation risk is <10%.
    
    

• Minimally invasive endoscopic procedure that enables precise myotomy.
• Most effective for type III achalasia, where spastic contractions extend beyond the LES.
• Success rates:
  • 92% at 2 years, superior to pneumatic dilatation.
  • More effective than Heller myotomy in long-term dysphagia control.
• Disadvantages:
  • Higher risk of reflux oesophagitis (41%) compared to surgical myotomy.
  • Requires expertise and high-volume centres for optimal outcomes.
    
    

Non-Surgical Management

• First-line for poor surgical candidates (frail, elderly, or those with severe comorbidities).
• Blocks acetylcholine release, lowering LES pressure and improving emptying.
• Efficacy:
  • Initial response >80%, but effects wane over time.
  • 68–75% symptom control at 2 years with repeat injections.
  • Long-term use may lead to antibody formation, reducing effectiveness.
    
    

• Used for temporary symptom relief while awaiting definitive treatment.
• Calcium channel blockers (e.g., nifedipine, verapamil) and nitrates (e.g., isosorbide dinitrate) relax the LES.
• Effectiveness:
  • Short-lived symptomatic relief.
  • Tolerance develops with chronic use, reducing long-term efficacy.
• Side effects: Hypotension, dizziness, headache.
  
  

• Gastrostomy for enteral feeding may be required in patients with severe dysphagia and malnutrition.
• Oesophagectomy is an option for patients with severely dilated (sigmoid) oesophagus or refractory disease despite repeated interventions.
  
  

Long-Term Outcomes of Treatment

• Remission rates:
  • 85.7% at 6–36 months, 61.9% at 37–60 months, and 40% beyond 60 months.
  • A retrospective study reported 72% at 12 months and 49% at 48 months.
• Durability:
  • Many patients experience symptom recurrence and require repeat dilatation.
  • Lower success rates in patients with severe oesophageal dilation or sigmoid-shaped oesophagus.
• Complications:
  • Gastro-oesophageal reflux disease (GORD) in 7% of patients, typically manageable with proton pump inhibitors (PPIs).
    
    

• Remission rates:
  • 75% at 5–10 years, with superior long-term symptom control compared to pneumatic dilatation.
• Surgical failure and reflux risk:
  • Postoperative reflux is common, necessitating long-term acid suppression therapy.
  • Fundoplication at the time of myotomy improves reflux control.
    
    

• Success rates:
  • 92% symptom relief at 2 years, significantly higher than pneumatic dilatation (54%).
  • Long-term data remain limited, but early studies suggest durable symptom control.
• Complications:
  • Higher rates of reflux oesophagitis (up to 41%), often requiring prolonged PPI therapy.
  • Some patients develop distal oesophageal dilation ("blown-out myotomy"), which can contribute to symptom recurrence.
    
    

Impact on Quality of Life

• Persistent dysphagia, chest pain, or reflux symptoms are common despite treatment.
• Long-term PPI use is often required, especially after POEM and myotomy.
• Health-related quality of life remains lower than in the general population, but interventions significantly improve symptoms and function.
  
  

Complications and Late-Stage Disease

• Without intervention, achalasia can progress to severe oesophageal dilation ("megaoesophagus"), necessitating oesophagectomy in some cases.
  
  

• Increased risk of oesophageal squamous cell carcinoma, likely due to chronic food stasis and mucosal irritation.
• Routine surveillance is not universally recommended, but some experts advocate endoscopic screening every 2–5 years.
  
  

Procedure-Related Complications

• Most commonly associated with pneumatic dilatation, occurring in up to 4% of cases.
• Higher risk with:
  • Larger balloon sizes (≥35 mm).
  • Repeated dilatations.
  • Pre-existing oesophageal diverticula or tortuous oesophagus.
• Management:
  • Small, contained perforations: Conservative approach with hospital observation, nil by mouth, broad-spectrum antibiotics.
  • Larger perforations: Require urgent surgical repair, especially if there is communication with the mediastinum or pleural/peritoneal cavities.
    
    

Aspiration Pneumonia

• Caused by chronic retention of oesophageal contents, leading to nocturnal aspiration.
• Incidence:
  • Up to 10% of hospitalised patients with achalasia develop pulmonary complications.
• Risk factors:
  • Long-standing oesophageal stasis.
  • Severe regurgitation.
  • Supine positioning after meals.
• Management:
  • Preventative strategies:
    • Elevating the head during sleep.
    • Avoiding meals before bedtime.
  • Treatment:
    • Antibiotics and supportive care for aspiration pneumonia.
      
      

Gastro-Oesophageal Reflux Disease (GORD)

• Most common long-term complication after surgical or endoscopic intervention.
• Incidence:
  • Up to 41% after POEM (peroral endoscopic myotomy).
  • 21% of patients develop severe reflux oesophagitis within 10 years after myotomy.
  • 7% of patients experience GORD after pneumatic dilatation.
• Complications of chronic reflux:
  • Barrett’s oesophagus in 13% of cases.
  • Peptic stricture formation in rare instances.
• Management:
  • Long-term proton pump inhibitor (PPI) therapy is often required.
  • Anti-reflux fundoplication is recommended at the time of myotomy to reduce reflux risk.
    
    

Oesophageal Carcinoma

• Increased risk of squamous cell carcinoma, attributed to chronic oesophageal stasis and mucosal irritation.
• Incidence:
  • 312.4 cases per 100,000 patient-years, significantly higher than in the general population.
  • A study found that oesophageal cancer was five times more likely in patients with achalasia than in matched controls.
• Challenges in diagnosis:
  • Progressive dysphagia may mask tumour growth, delaying detection until advanced stages.
• Surveillance:
  • No universally accepted guidelines for routine endoscopic screening.
  • A physician survey reported that 82% believed achalasia increases lifetime cancer risk, and 89% supported screening every 2–5 years.
    
    

1. Allgrove A, Clayden GS, Grant DB, et al. Achalasia, alacrima, and adrenal insufficiency: a new syndrome. J Clin Endocrinol Metab. 1978;47(2):572-578.
2. Ates F, Vaezi MF. The pathogenesis and management of achalasia: current status and future directions. Gut Liver. 2015;9(4):449-63.
3. Birgisson S, Galinski MS, Goldblum JR, et al. Achalasia is not associated with measles or known herpes and human papilloma viruses. Dig Dis Sci. 1997;42(2):300-6.
4. Birgisson S, Richter JE. Achalasia in Iceland, 1952-2002: an epidemiologic study. Dig Dis Sci. 2007;52(8):1855-60.
5. Boeckxstaens GE, Zaninotto G, Richter JE. Achalasia. Lancet. 2014;383(9911):83-93.
6. Borotto E, Gaudric M, Danel B, et al. Risk factors of oesophageal perforation during pneumatic dilatation for achalasia. Gut. 1996;39(1):9-12.
7. Carlson DA, Gyawali CP, Kahrilas PJ, et al. Esophageal motility classification can be established at the time of endoscopy: a study evaluating real-time functional lumen imaging probe panometry. Gastrointest Endosc. 2019;90(6):915-23.
8. Duffield JA, Hamer PW, Heddle R, et al. Incidence of achalasia in South Australia based on oesophageal manometry findings. Clin Gastroenterol Hepatol. 2017;15(3):360-5.
9. Facco M, Brun P, Baesso I, et al. T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens. Am J Gastroenterol. 2008;103(7):1598-606.
10. Fox M, Hebbard G, Janiak P, et al. High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry. Neurogastroenterol Motil. 2004;16(5):533-42.
11. Furlanetto EJ, Prakash C, Farkas A, et al. Association of achalasia with measles and varicella zoster virus infections. Gastroenterology. 2012;143(6):1234-41.
12. Gockel I, Eckardt VF, Schmitt T, et al. Pseudoachalasia: a case series and analysis of the literature. Scand J Gastroenterol. 2005;40(4):378-85.
13. Gockel I, Schumacher J, Weisser B, et al. Genetic susceptibility to achalasia is associated with HLA-DQ and –DR alleles. Gastroenterology. 2010;138(4):1558-62.
14. Goldblum JR, Rice TW, Richter JE. Histopathologic features in oesophagectomy specimens from patients with achalasia. Gastroenterology. 1996;111(3):648-54.
15. Harvey PR, Thomas T, Chandan JS, et al. Incidence, morbidity and mortality of patients with achalasia in England: findings from a study of nationwide hospital and primary care data. Gut. 2019;68(5):790-5.
16. Holloway RH, Dodds WJ, Helm JF, et al. Integrity of cholinergic innervation to the lower oesophageal sphincter in achalasia. Gastroenterology. 1986;90(4):924-31.
17. Howard PJ, Maher L, Pryde A, et al. Five-year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh. Gut. 1992;33(8):1011-5.
18. Ho KY, Tay HH, Kang JY. A prospective study of the clinical features, manometric findings, incidence and prevalence of achalasia in Singapore. J Gastroenterol Hepatol. 1999;14(8):791-5.
19. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for oesophageal achalasia. Endoscopy. 2010;42(4):265-71.
20. Kahrilas PJ, Kishk SM, Helm JF, et al. Comparison of pseudoachalasia and achalasia. Am J Med. 1987;82(4):439-46.
21. Katzka DA, Castell DO. Review article: an analysis of the efficacy, perforation rates and methods used in pneumatic dilation for achalasia. Aliment Pharmacol Ther. 2011;34(8):832-9.
22. Kim E, Lee H, Jung HK, et al. Achalasia in Korea: an epidemiologic study using a national healthcare database. J Korean Med Sci. 2014;29(4):576-80.
23. Leeuwenburgh I, Scholten P, Alderliesten J, et al. Long-term oesophageal cancer risk in patients with primary achalasia: a prospective study. Am J Gastroenterol. 2010;105(10):2144-51.
24. Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology. 2008;135(5):1526-33.
25. Park W, Vaezi MF. Etiology and pathogenesis of achalasia: the current understanding. Am J Gastroenterol. 2005;100(6):1404-14.
26. Ponds FA, Fockens P, Lei A, et al. Effect of peroral endoscopic myotomy vs pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: a randomised clinical trial. JAMA. 2019;322(2):134-44.
27. Reynolds JC, Parkman HP. Achalasia. Gastroenterol Clin North Am. 1989;18(2):223-55.
28. Richter JE, Castell DO. Review article: the pathogenesis of achalasia – evidence for a genetic and autoimmune basis. Aliment Pharmacol Ther. 2000;14(7):787-801.
29. Sadowski DC, Ackah F, Jiang B, Svenson LW. Achalasia: incidence, prevalence and survival. A population-based study. Neurogastroenterol Motil. 2010;22(9):e256.
30. Samo S, Carlson DA, Gregory DL, et al. Incidence and prevalence of achalasia in central Chicago, 2004-2014, since the widespread use of high-resolution manometry. Clin Gastroenterol Hepatol. 2017;15(3):366-73.
31. Schuffler MD. Chronic intestinal pseudo-obstruction syndromes. Med Clin North Am. 1981;65(6):1331-51.
32. Stein CM, Gelfand M, Taylor HG. Achalasia in Zimbabwean blacks. S Afr Med J. 1985;67(7):261-2.
33. Taylor IL, Sells RA, McConnell RB, et al. Serum gastrin in patients with chronic renal failure. Gut. 1980;21(12):1062-7.
34. Vanuytsel T, Lerut T, Coosemans W, et al. Conservative management of oesophageal perforations during pneumatic dilation for idiopathic oesophageal achalasia. Clin Gastroenterol Hepatol. 2012;10(2):142-9.
35. Vaezi MF, Baker ME, Richter JE. Diagnosis and management of achalasia. Am J Gastroenterol. 2005;100(6):1404-14.
36. Verne GN, Sallustio JE, Eaker EY. Anti-myenteric neuronal antibodies in patients with achalasia: a prospective study. Dig Dis Sci. 1997;42(2):307-13.
37. Wong RK, Maydonovitch CL, Metz SJ, Baker JR Jr. Significant DQw1 association in achalasia. Dig Dis Sci. 1989;34(3):349-53.
38. Wouters MM, Lambrechts D, Becker J, et al. Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia. Gut. 2014;63(9):1401-9.