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Updates on the management of Achalasia
Joint Hospital Surgical Grand Round
21 July 2012
Lok Hon Ting (NDH)
Pathophysiology
• Motor disorder of the esophagus characterized by:– Incomplete or absent relaxation of LES
– Aperistalsis of esophageal body
• Destruction of ganglion cells present in the esophageal wall and LES– > Impaired relaxation of LES
• Cause unknown, proposed etiology:– Viral hypothesis (VZV, HSV-1)
• Jones DB. J Clin Pathol 1983. Robertson CS. Gut 1993
– Autoimmune hypothesis
Clinical manifestation
• Epidemiology– Prevalence 1 per 100,000– No gender predilection
• Sadowski DC et al. Neurogastroenterol Motil 2010
• Symptoms:– Dysphagia – Both liquids and solids– Regurgitation +/- Pulmonary Aspiration– Chest pain / Heartburn in ~50% patient
• Spechler SJ et al. Gut 1995
– Weight Loss
• 16-fold increased risk of Ca Esophagus• Sandler RS et al. JAMA 1995
Investigation
• OGD– tight cardia and food residual in
esophgaus
• Barium Swallow - Sensitivity 95%
– Ott DJ et al. AJR Am J Roentgenol 1987
• Esophageal manometry– absence of any esophageal peristaltic
contractions– failure of the LES to relax to less than
8 mm Hg– Gideon RM. Gastrointest Endosc Clin N Am 2005
Treatment Modalities
Pharmacological treatment• Nitrates, Calcium channel blockers
• Evidence:
• Conclusion: Ineffective
Study Design Medication LES Pressure Dysphagia symptoms
Traube et alAm J Gastroenterol 1989
RCT PO VerapamilPO Nifedipine
↓ No significant difference
Triadafolopoulos et alDig Dis Sci 1991
RCT SL Nifedipine ↓ No significant difference
Botulinum toxin injection
• Endoscopic injection at 4 quadrants of LES
• Inhibit release of acetylcholine in muscle synapse
• First used by Pasricha in 1993
Botulinum toxin injection
• Promising short term effect
• Symptoms recurrence beyond 6 months follow up
• 76% response to 2nd injection, but not to further injection
Farnoosh Farrokhi etal. Orphanet Journal of Rare Diseases 2007
Botulinum toxin injection
• Side effects 0 – 33%– Chest pain, reflux symptoms and rash
• D Gui. Aliment Pharmacol Ther 2003
• Subsequent myotomy more difficult• Pehlivanov N. Neurogastroenterol Motil 2006
• Conclusion:– Safe and effective in short term symptoms relief– For elderly or frail patient only
Pneumatic dilatation
• To disrupt circular muscle fiber of LES without full thickness perforation
• First used by Sir Thomas Willis since the condition was first recognized
• Rigiflex Polyethylene balloon
(30, 35, 40mm diameter)
Pneumatic dilatation
Guilherme M. Campos et al. Annals of Surgery 2009
Pneumatic dilatation
• A pool of 1065 patients in 15 controlled series
• Mean follow-up 30.8 months (6 – 111 months)
• Rate of symptom improvement decreases with FU duration
• Perforation rate: 1.6% (0 – 8%)
• Subsequent treatment after index dilatation:– Repeated dilatation 25%– Myotomy 5%
84.80%
73.80%68.20%
58.40%
< 1 month 6 months 12 months > 36 months
Heller’s myotomy
• First described by Ernest Heller in 1914– Cutting the anterior and posterior aspect of LES– Current practice: myotomy over anterior aspect only
• Minimally invasive approach 1990s– Thoracoscopic versus laparoscopic– Laparoscopic approach: less morbidity and quicker recovery
• Richter JE. Gastroenterol hepatol 2008
– > standard approach
Heller’s myotomy
Bresadola et al. Surg Laparosc Endoscc Percutan Tech 2012
Heller myotomy
• A pool of 1708 patients in 19 publications
• Follow-up duration: 4.78 year (range: 0.5 -11.2 years)
• Symptom response rate: 79.3% (range: 47 – 97%)
• GERD: – With fundoplication: 15.2% (range: 0 – 44%)– Without fundoplication: 37% (range: 11 – 60%)
• Response rates decreased in patients with longer FU– > 7 years: 80% > 10 years: 74% > 20 years 65%
Csendes. Ann Surg 2006
Heller’s myotomy and anti reflux surgeryStudy Design Patient
no.Acid Reflux Dysphagia /
Esophageal emptying
Richards et al. Ann Surg 2004
Prospective double-Blind RCT
H: 21 H: 47.6% No significant difference in dysphagia score
H + D: 22 H + D: 9.1% (p = 0.005)
Rice et al. J Thorac Cardiovasc Surg 2005
Retrospective non-randomized study
H: 61 H + D:• ↓ exposure time • ↓ number of episode• ↓ longest episode time(p < 0.05)
H + D did not impair esophageal emptying (p = 0.6)
H + D: 88
D Falkenback et alDis Eso 2003
RCT H: 10 H: 47.6% No significant difference in dysphagia score(p = 0.82)
H + N: 10 H + D: 9.1%(p = 0.005)
Rebecchi et al Ann Surg 2008
RCT H + D: 72 5.6% 2.8%
H + N: 72 0% (p = 0.07) 15% (p < 0.001)
Conclusion: Heller’s myotomy with concomitant Dor’s fundoplication is the procedure of choice
Pneumatic Dilatation versus Heller’s Myotomy
• A Csendes et al. Guts 1989
– Randomized controlled trial
– Subjects: Pneumatic dilatation (n = 39)
Open Heller’s myotomy + Dor’s fundoplication (n =42)
– Conclusion:• The study shows that surgical treatment offers a better final
clinical result than pneumatic dilatation with the Mosher bag
Pneumatic Dilatation versus Lap Heller’s Myotomy
• S Kostic et al. World J Surg 2006
– Randomized controlled trial
– Subjects: Graded pneumatic dilatation (n = 26)
Heller’s myotomy + toupet’s fundoplication (n =25)
– Primary outcome: Treatment failure rate
– 2 Perforations after pneumatic dilatation
Pneumatic Dilatation versus Lap Heller’s Myotomy
• Lopushinsky SR et al. JAMA 2006
– Retrospective longitudinal study
– Subjects: Pneumatic dilatation 1181 (80.8%)
Surgical myotomy 280 (19.2%)
– Primary outcome: use of subsequent intervention
– Differences in risk were observed only when subsequent pneumatic dilatation was included as an adverse outcome
Pneumatic Dilatation versus Lap Heller’s Myotomy
Design Patient no. Symptom improvement (% patient)
GERD Perforation
6 – 12 months
2 years 6 years
Vela MF et alClin gastroenterol hepatol 2006
Cross sectional study
Single PD: NR
62% 28% 4%
Graded PD: 106
90% 44%
HM: 73 89% 57% 36%
GE Boechxstaens et alN Engl J Med 2011
RCT Graded PD: 95
90% 86% 15% 4%
HM + Dor: 106
93% 90% 23%(p=0.28)
12% mucosal tear
Pneumatic Dilatation versus Heller’s Myotomy
• Emerging evidence showing comparable result between pneumatic dilatation and Heller’s Myotomy
– Improvement of dilatation devices and technique
– Definition of treatment failure• Some of the latest studies accept repeated dilatation as part of the
dilatation program, instead of treatment failure
– Both pneumatic dilatation and Heller’s Myotomy are reasonable choices of treatment if patients accept repeated dilatation
Per Oral Endoscopic Myotomy • Natural orifice transluminal endoscopic
surgery -> Novel approach for Achalasia
• The concept of Submucosal tunneling and procedure was described by Samiyama K in 2007
• Endoscopic myotomy was first reported by Pasricha et al. in a porcine model
– Endoscopy 2007
Per Oral Endoscopic Myotomy
• First series of 17 patients with achalasia treated by P.O.E.M., reported by Inoue et al
– Endoscopy 2010
Per Oral Endoscopic Myotomy• 17 patients
– seven women, ten men– mean age 41.4 years, range 18–62
• Long submucosal tunnel created (mean 12.4cm)
• Mean myotomy length = 8.1cm
• Dysphagia symptoms score: 10 1.3 (p = 0.0003)
• LES pressure: 52.4mmHg 19.8mmHg (p = 0.0001)
Per Oral Endoscopic Myotomy
• Experience from various centers
Study Patient no.
Myotomy length (cm)
Dysphagia score
LES Pressure (mmHg)
Morbidity
Inoue et al. Endoscopy 2010
17 8.1 Pre: 10Post: 1.3(p = 0.0003)
Pre: 52.4Post: 19.9(p = 0.0001)
Penetration of cardiac mucosa in 2 patients, no clinical manifestation
Zhou PH et al.Chi J Gastroint Surg 2011
42 9.5 Significant symptoms improvement
Not reported Nil
Costamagna et al Digestive and Liver Disease 2012
7 10.2 Eckardt ScorePre: 7.11 month: 1.1(p = 0)
Pre: 45.1Post: 16.9(p = 0)
Nil
Conclusion
• Laparoscopic cardiomyotomy + partial fundoplication is the standard treatment for achalasia
• Pneumatic dilatation is reasonable alternative if patient accepts risk of repeated dilatation
• Botox injection is only recommended for elderly and frail patients
Conclusion
• POEM is a novel approach showing promising short term results
• Long term follow up needed– rate of symptoms recurrence– need for subsequent intervention– incidence of GERD– complication profile
Thank you