Achalasia Cardia

Definition

Pathophysiology

• The degree of ganglion cell loss parallels disease duration, likely progressing from EGJ outflow obstruction → Type II → Type I → end-stage achalasia
• Both excitatory (cholinergic) and inhibitory (NO/VIP-mediated) ganglion neurons are affected, but inhibitory neuron dysfunction is an early manifestation
• Loss of inhibitory neurons explains the two core abnormalities: impaired LES relaxation and aperistalsis
• Muscle strips from the LES fail to relax on ganglionic stimulation; paradoxically, CCK (which normally relaxes the LES via inhibitory neurons) increases LES pressure in achalasia
• The root cause is increasingly understood as an autoimmune process in genetically susceptible individuals - cytotoxic T-cell infiltration in the myenteric plexus, antibodies against myenteric neurons, and an association with specific HLA alleles
• A latent HSV-1 infection is the suspected trigger for the autoimmune response

Classification (Chicago Classification - HRM Subtypes)

Clinical Features

• Onset is typically gradual, often present for years before diagnosis
• Regurgitant is non-bilious, non-acid, mixed with saliva, and may contain food eaten hours or days earlier
• "Heartburn" is caused by bacterial fermentation of retained food - not true GERD; this leads to misdiagnosis and inappropriate PPI therapy (average 29-month delay in one study)
• With advanced disease: bronchopulmonary complications from aspiration occur in up to 10%
• Rare: stridor/airway compromise from esophageal dilatation compressing the membranous trachea

Diagnosis

1. Endoscopy (EGD)

• First test usually done for dysphagia
• Normal in ~40% of patients
• May show: retained food/saliva, stasis esophagitis, Candida infection
• Mandatory to exclude pseudoachalasia (malignancy at the GEJ)

Barium swallow in achalasia showing distal esophageal narrowing, air-fluid level, poor emptying, and tertiary contractions - Sabiston Textbook of Surgery

2. Barium Swallow (Esophagram)

• Classic appearance: "bird's beak" or rat-tail tapering at the distal esophagus
• Dilated, tortuous esophagus with stasis of contrast
• Air-fluid level, tertiary contractions
• Can reveal additional pathology (diverticulum, sigmoid deformity)
• Normal in ~30% of early cases
• Important for planning treatment (degree of dilatation, axis of esophagus)

3. High-Resolution Esophageal Manometry (HRM)

• Gold standard for diagnosis
• Classic findings: elevated integrated relaxation pressure (IRP), aperistalsis
• Allows subtyping into Types I, II, III (Chicago Classification)
• Critical for treatment planning

4. Additional Tests

• Ambulatory pH monitoring: for patients with heartburn - differentiates true GERD from fermentation-induced pseudo-reflux (look for slow pH drift vs. discrete reflux events)
• FLIP (Functional Lumen Imaging Probe): assesses esophageal compliance and distensibility using impedance planimetry; corroborates HRM findings; useful to assess effect of treatment

Treatment

1. Pharmacologic Therapy (temporizing only)

• Calcium channel blockers (nifedipine 30-40 mg/day sublingually before meals): modest benefit, side effects common (flushing, dizziness, edema)
• Nitrates (isosorbide dinitrate sublingually): reduce LES pressure; limited efficacy, headaches common
• Sildenafil (50 mg): blocks PDE-5, reduces LES pressure; peaks at 15-20 min, lasts <1 hour; limited practical use
• Overall: minimal/temporary benefit; best for bridging or non-surgical candidates

2. Botulinum Toxin Injection

• Injected into 4 quadrants of the LES (standard dose 80-100 units)
• Inhibits ACh release from cholinergic terminals, reducing LES pressure
• 66% improvement in dysphagia at 6 months; minimal efficacy at 1 year
• Repeat injections cause fibrosis, complicating future surgery
• Best reserved for elderly or frail patients who are poor surgical/endoscopic candidates

3. Pneumatic Dilation (PD)

• Requires LES distension to at least 3 cm (Rigiflex balloons: 3.0, 3.5, 4.0 cm)
• Disrupts circular muscle of the sphincter
• Done over a guidewire under fluoroscopy with conscious sedation
• ~90% effective; risk of esophageal perforation ~1%
• Preferred initial treatment for Type II achalasia (100% efficacy in European RCT vs 93% for LHM)
• Less effective for Type III (only 40% success)

4. POEM (Per-Oral Endoscopic Myotomy)

• 4 steps: submucosal injection + mucosal incision (10-12 cm above GEJ) → submucosal tunneling past GEJ by 2-3 cm → myotomy of circular fibers (preserving longitudinal) → mucosal closure with clips/sutures
• Symptom relief >90% of patients at 1-2 years
• Achilles heel: very high rate of postoperative GERD (~47-57%) because no fundoplication is added
• Preferred for Type III achalasia because a longer myotomy onto the esophageal wall is possible
• Equivalent efficacy to LHM for Types I and II

5. Laparoscopic Heller Myotomy (LHM) + Partial Fundoplication

• Long-standing gold standard surgical treatment
• Done laparoscopically; myotomy of LES muscle with partial fundoplication (Dor or Toupet) added
• Clinical success ~90% at 2 years
• Much lower GERD rate than POEM: ~11-20% vs 47-57%
• The addition of fundoplication reduces postoperative reflux from 48% to 9%
• Preferred over POEM for young patients where lifelong GERD exposure (Barrett esophagus, adenocarcinoma risk) is a concern

Treatment Summary by Subtype

Complications and Long-term Issues

Post-treatment GERD

• After POEM: ~50-57% develop pathologic reflux
• After LHM without fundoplication: ~48%
• After LHM + Dor fundoplication: ~9%
• Long-term GERD can cause esophagitis, Barrett's esophagus, and adenocarcinoma

Squamous Cell Carcinoma Risk

• 17-fold increased risk compared to age-matched controls; however, the absolute annual incidence remains very low (~0.15%)
• Tumors develop many years after diagnosis in massively dilated esophagus with stasis esophagitis
• Latest ASGE guidelines: do not advocate routine endoscopic surveillance; however, if considered, begin 15 years after symptom onset

Treatment Failure

• Options: repeat dilation, POEM, Heller myotomy, or reoperation
• Reoperation is less effective than the initial procedure
• In extreme cases: esophagectomy

Pseudoachalasia

• Rapid onset of dysphagia (< 1 year)
• Age > 60
• Significant weight loss
• Incomplete LES relaxation without aperistalsis on manometry

Recent Evidence (2024-2026)

• FLIP-guided assessment is increasingly used to compare outcomes after POEM vs. Heller myotomy (PMID 40399616)
• Same-day discharge after POEM is safe and feasible based on a 2026 meta-analysis (PMID 42377530)