Ministry of Health of the Republic of Moldova

Ministry of Health of the Republic of Moldova State University of Medicine and Pharmacy "Nicolae Testemiţanu" Esophageal Achalasia Department of Surgery Prof. Dr. A. Hotineanu

Objectives • Esophageal Anatomy and Innervation • Esophageal Motility disorders • Achalasia - Pathophysiology - Epidemiology - Symptomatology - Diagnosis -Treatment -Complications • Case Report

Anatomy of the Esophagus • Upper esophageal sphincter (UES) and proximal 3 -4 cm is striated muscle. • Distal 2/3 and lower esophageal sphincter (LES) is smooth muscle. • Circular and longitudinal muscle layer.

Innervation of Esophagus • Afferent (esophagus to swallowing center vagus) • Efferent to smooth muscle from dorsal motor nucleus of vagus (recurrent laryngeal branch of vagus innervates cervical esophagus; thoracic vagal trunk innervates thoracic esophagus)

Primary Esophageal Motility Disorders • Present clinically with dysphagia (difficulty swallowing), odynophagia (pain when swallowing) and/or chest pain. • Primary (no known underlying cause or precipitating factor) - Achalasia - Diffuse Esophageal Spasm - Hypercontracting Esophagus * Hypertensive Esophagus (Nutcracker Esophagus) * Hypertensive LES -Hypocontracting Esophagus * Ineffective Esophageal Motility * Hypotensive LES

Secondary Esophageal Motility Disorders • Secondary (known cause) - collagen vascular disease (scleroderma) - Diabetes - Chagas’ disease - Amyloidosis - Alcoholism - MS - Aging process - Invasive Cancer

Achalasia: Introduction • Achalasia – Greek for “does not relax” • is a primary esophageal motility disorder characterized by failure of LES relaxation and loss of peristalsis in the distal esophagus. • Emptying of esophagus occurs once pressure of the intraluminal material exceeds the pressure of the LES. • These abnormalities cause a functional obstruction at the gastro esophageal junction. • Relatively rare. Incidence <1/100, 000 per year. Incidence peaks in 3 rd and 7 th decades. No gender differences.

Achalasia: Pathophysiology • LES pressure and relaxation are regulated by excitatory (acetylcholine, substance P. . ) and inhibitory (nitric oxide, vasoactive intestinal peptide…) neurotransmitters. • Achalasia results from degeneration of intramural innervation in the esophagus decreased numbers of ganglion cells in myenteric plexus in patients • Remaining ganglion cells in myenteric plexus are surrounded by lymphocytes and eosinophils. • Inhibitory neurons are selectively destroyed (nitric oxide producing neurons) net increased tone in LES and aperistalsis in esophageal body. • Imbalance between excitatory and inhibitory elements.

Histopathology of Achalasia • (a) Normal myenteric plexus demonstrating multiple ganglion cells and minimal lymphocytic infiltration. (b) Mild myenteric inflammation. Ganglion cells can be identified. (c) Moderate myenteric inflammation with lymphocytic infiltrate. Ganglion cells are absent. (d) Severe myenteric inflammation with lymphocytes densely clustered within the myenteric plexus. Ganglion cells are absent.

Achalasia: Etiology • Primary Achalasia: Etiology unknown - Hereditary, degenerative, autoimmune and infectious causes have been proposed. -Autoimmune- HLA-DQw 1 associated with ~4× relative risk in one study. Also, affected pts often have circulating antibodies to enteric neurons. - infectious- Some suggest chronic infection with herpes zoster or measles viruses. • Secondary Achalasia: Due to underlying pathology (e. g. , Chagas) • Pseudoachalasia: usually malignancy (carcinoma of gastric cardia in >50% of cases)

Secondary form of Achalasia • • • Allgrove’s syndrome (AAA syndrome) Hereditary cerebellar ataxia Familial achalasia Sjögren’s syndrome Sarcoidosis Post-vagotomy Post-fundoplication Autoimmune polyglandular syndrome type II • Achalasia with generalized motility disorder • • MEN IIb (Sipple’s syndrome) Neurofi bromatosis (von Recklinghausen’s disease) Chagas’ disease (Trypanosoma cruzi) Paraneoplastic syndrome (anti-Hu antibody) Parkinson’s disease Amyloidosis Fabry’s disease Hereditary cerebellar ataxia • • Achalasia with associated Hirschsprung’s disease Hereditary hollow visceral myopathy • Achalasia secondary to cancer (pseudoachalasia) • • • • Squamous cell carcinoma of the esophagus Adenocarcinoma of the esophagus Gastric adenocarcinoma Lung carcinoma Leiomyoma Lymphoma Breast adenocarcinoma Hepatocellular carcinoma Reticulum cell sarcoma Lymphangioma Metastatic renal cell carcinoma Mesothelioma Metastatic prostate carcinoma Pancreatic adenocarcinoma

Achalasia: Clinical Manifestation • Dysphagia for solids (91% of pts) and liquids (85% of pts) --most significant symptom. - Difficulty Belching (85%) - Weight loss (usually 5 to 10 kg) - Regurgitation (undigested food, especially when lying flat at night) - Chest Pain - Heartburn - Patients may offer history of being a “slow eater” or the “last to finish their meal” and may have adopted maneuvers to aid esophageal emptying (throw shoulders back, lift neck, walk after meals, etc). - Globus sensation in esophagus - Hiccups • There is a considerable delay btw. onset of symptoms and diagnosis.

Achalasia: Diagnosis • Patients with a history suggestive of achalasia may undergo: - Radiographic Evaluation - Manometric Evaluation - Endoscopic Evaluation

Radiographic studies 1. Normal chest x-ray: -markedly dilated Esophagus - Air-fluid level in esophagus on upright view - Tertiary non-stripping peristalsis or aperistalsis - Absent gastric air bubble

Achalasia on Plain Film • Widening of mediastinum due to dilated esophagus • Absence of gastric air bubble due to failure of LES relaxation

2. barium esophagram with fluoroscopy (best method) -Typical for achalasia is the smooth narrowing of the distal esophagus at the level of the lower esophageal sphincter with the characteristic “bird beak” or “champagne glass” appearance. -The proximal esophagus may be dilated and frequently a column of barium forms above the LES as a result of the poor relaxation and opening of the sphincter. -The contrast material passes slowly into the stomach as the LES opens intermittently (>5 sec. ).

Normal vs. Achalasia on Ba. Sw

Esophageal manometry • Measurement of pressures in esophagus -very often performed to confirm cases, even with strong clinical or radiographic evidence. -characteristic findings: - elevated resting LES pressure - incomplete LES relaxation - Aperistalsis (smooth muscle portion of esophagus). A swallow may be followed by no contraction or by simultaneous contractions. Some patients have high amplitude simultaneous contractions, termed “vigorous” achalasia.

Esophageal manometry

Esophagogastroduodenoscopy (EGD) • EGD: - To rule out cancer of the gastriesophageal junction or fundus. (if a tumor suspected) - Endoscopy normal ca. 44% of patients with achalasia - Difficulty traversing the esophagogastric junction should raise suspicion for pseudoachalasia due to neoplastic infiltration of the distal esophagus or gastric cardia.

Other Investigation • Prolonged esophageal p. H monitoring is important for the following reasons: - To rule out GERD (Gastroesophageal reflux disease) - To determine if abnormal reflux is being caused by treatment. • Endoscopic Ultrasound if a tumor is suspected

HRM • High Resolution esophageal Manometry (HRM) improves the accuracy of esophageal manometry • Manometric variants of achalasia exist: - achalasia with minimal esophageal pressurization (type I, classic), - achalasia with esophageal compression (type II), - achalasia with spasm (type III). ******type II and III= “Vigorous Achalasia” • They are distinct in terms of their responsiveness to medical or surgical therapies - type II = strong posistive predictor of response - type III = strong negative predictor of response.

HRM

HRM

Treatment • Goal: 1. Relieve symptoms by eliminating the outflow resistence 2. Food bolus can travel through the aperistaltic body of the esophagus by gravity. • This can be accomplished most effectively by pneumatic dilation and surgical myotomy or less effectively by pharmacological agents injected endoscopically into the LES (botulinum toxin) or taken orally (calcium channel blockers and nitrates).

Medical Therapy • Patients who are awaiting or unable to tolerate more invasive treatment modalities. • Calcium channel blockers and nitrates decrease LES pressure: - Nifedipine 20 -30 mg - Isosorbide dinitrate 5 -10 mg daily Approximately 10% of patients benefit from this treatment.

Endoscopic Intrasphincteric Injection of Botulinum Toxin • To block release of acetylcholine at the level of the LES. • Only 30% of patients treated endoscopically still have relief of dysphagia 1 year after treatment. • This treatment can cause an inflammatory reaction at the level of the gastroesophageal junction, making a subsequent myotomy very difficult. • A total of 80 to 100 U of the toxin is injected in divided doses into the four quadrants of the LES.

Pneumatic dilatation • is the most effective nonsurgical treatment option for patients with achalasia. • Is recommended treatment in those sporadic cases in which surgery is not appropriate. • A balloon is inflated at the level of the gastroesophageal junction to blindly rupture the muscle fibers while leaving the mucosa intact. The success rate is 70 -80%, and perforation rate is approximately 5%.

Pneumatic dilatation • Factors that negatively affect the treatment response: - Age <37. 5 years - Admission LESP >30 mm. Hg - LESP after first balloon >17 mm. Hg - Balloon number >2

Recommended Technique for Pneumatic Dilation Using the Graded Balloons 1. 2. 3. 4. Fasting >12 h before procedure. Esophageal lavage with a large-bore tube (if needed). Sedation and endoscopy in IId position. Guidewire positioned in stomach and balloon passed over the guidewire. 5. Initial dilation with 3 cm diameter balloon; subsequent progression to 3, 5 cm and 4 cm balloon may be required at separate sessions. 6. Accurate placement of balloon across gastroesophageal junction fluoroscopically

Recommended Technique for Pneumatic Dilation Using the Graded Balloons 7. Balloon distention to obliterate the waist, which usually requires 7 -10 psi 8. Gastrograffin study followed by barium swallow to exclude esophageal perforation 9. Observation for 4 h for chest pain and fever 10. Discharge with follow-up in 1 mo.

Surgical treatment • Surgical Myotomy (Heller, Laparoscopic): - Weakens LES by cutting muscle fibers - Thoracotomy necessary if not laparoscopic - 70 -85% success at 10 yrs for modified Heller - Surgical myotomy for achalasia involves performing an anterior myotomy across the LES (Heller’s myotomy) usually associated with an antireflux procedure.

• During the procedure, the patient is put under general anesthesia. Five or six small incisions are made in the abdominal wall and laparoscopic instruments are inserted. The myotomy is a lengthwise cut along the esophagus, starting above the LES and extending down onto the stomach a little way. The esophagus is made of several layers, and the myotomy only cuts through the outside muscle layers which are squeezing it shut, leaving the inner muscosal layer intact.

Early postoperative dysphagia - Caused by incomplete myotomy Periesophageal inflammation Underlying esophageal dysmotility Esophageal enlargement with sigmoid deformity, or Mechanical obstruction by a fundoplication, paraesophageal hernia, or crural diaphragmatic hiatus repair.

Delayed recurrence of postoperative dysphagia • • • Ø Development of a recurrent high pressure zone at the LES. Peptic stricture complicating acid reflux. An obstructed or slipped fundoplication. Progressive megaesophagus with sigmoid deformity, or Esophageal cancer can manifest. In case of postoperative dysphagia due to an incomplete myotomy or a recurrent high pressure zone, pneumatic dilation can be employed as an alternative to redo surgery.

Complications associated with Achalasia • Progressive malnutrition • Pneumonic Aspiration • Epiphrenic diverticula - Immediately proximal to the LES - Potential therapeutic technical challenges and perforation risks. • Esophageal cancer - SCC > adeno - No difference in treatment groups - 16 -fold increased risk during years 1 to 24 after initial diagnosis.

Case Report A 66 -year-old man presented with a history of recurrent low-grade fever, cough, mucopurulent sputum, dyspnea, loss of appetite and loss of weight for the past two years. There was no history of hemoptysis. He had been receiving symptomatic treatment at his native place but was not relieved. The initial investigation started with a frontal chest radiograph. The chest radiograph was suggestive of a right upper zone mass lesion with widening of mediastinum but was inconclusive

Barium swallow was performed which showed dilated, tortuous esophagus Blood test and biochemical test was normal, and the patient represents just with mitral valve regurgitation and slightly left atrium dilatation with presence of atrial fibrillation. After the conformation of diagnose by barium enema the patient was scheduled for surgery in two days. Heller’s myotomy was performed, and after several days the patient was sent home without any complications.

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