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