Illustrated presentation concerning achalasia cardia, presented on the 2nd february 2016 during a medical staff at CHU Mont-Godinne Dinant UCL Namur.

1. Achalasia
• Introduction
• Epidemiology
• History
• Pathophysiology
• Pathology
• Animal models
• Clinical description
• Diagnosis
• Differential diagnosis
• Natural history
• Treatment
• Comparison of treatments
• Management algorithms
• Conclusion
ICD-10: K22.0
a-chalasia, from Ancient Greek
– α-: a-, « not »
– χάλασις (khálasis): chalasia,
« relaxation »
Fabien Wuestenberghs 2nd february 2016

2. Epidemiology
Sadowski DC, Ackah F, Jiang B, Svenson LW. Achalasia:
incidence, prevalence and survival. A population-based study.
Neurogastroenterol Motil. 2010 ; 22 : e256-261.
O’Neill OM, Johnston BT, Coleman HG. Achalasia: A review of clinical
diagnosis, epidemiology, treatment and outcomes. World J
Gastroenterol. 2013 ; 19 (35) : 5806-5812.
(Alberta 1996–2007)

3. History
• 1672: first description by Sir Thomas
Willis
• 1881: described as Cardiospasm by
von Mikulicz
• 1898: first “pneumatic” dilation by
Russel
• 1913: Ernst Heller performed the first
esophagomyotomy
• 1929: term Achalasia by Hurt and
Rake
• 1937: F.C. Lendram changed the
name from cardiospasm to Achalasia
• 1950s/1960s: approach via
thoracoscopy popularized by Ellis
• 1962: Dor reports the first anterior
partial fundoplication
• 1963: Toupet reports first posterior
partial fundoplication
• 1991: first laparoscopic Hellers’
performed by Shimi in UK
• 1994: Pasricha introduces Botox
injection
• 2010: first POEM by Inoue

4. Pathophysiology
Ghoshal UC, Daschakraborty SB, Singh R. Pathogenesis of achalasia cardia. World J Gastroenterol. 2012 ; 18 : 3050-3057.
genetic predisposition
autoimmune mechanisms environmental factors
ACHALASIA
Familial cases
• Allgrove (Triple-A) syndrome
• Down’s syndrome
• Congenital central hypoventilation
syndrome
Multiple genetic mutations
- NOS1 (nitric oxide synthase 1 gene)
- VIP receptor 1
- IL23R
- IL10 promoter
- IL33
- PTPN22 (protein tyrosine
phosphatase non-receptor 22)
Booy JD, Takata J, Tomlinson G, Urbach DR. The prevalence of autoimmune disease in patients
with esophageal achalasia. Dis Esophagus. 2012 ; 25 : 209-213.
Boeckxstaens GE. Achalasia: virus-induced euthanasia of neurons? Am J Gastroenterol. 2008 ;
103 : 1610-1612.
HSV-1

5. Pathology
• Loss of ganglion cells
• Inflammation
• Fibrosis in severe cases
• Thickening of the inner circular
layer of the muscularis propria
Kaiyo Takubo. Pathology of the Esophagus
2nd Edition. An Atlas and Textbook.

6. Animal models
Adult North American opossums
(Didelphis virginiana)
 Gore-Tex band placed around the
gastroesophageal junction
Gauze soaked with benzalkonium chloride
(BAC) wrapped around the abdominal
portion of the esophagus in rats,
opossum or dogs
Surgical vagotomy in opossums, dogs and
primates
Mega-esophagus :
- Transgenic (Pvrl3-Cre) rats
- Rat strain BDE/HAN
- Stock colony of Srl:BHE rats
Genetically modified mice lines
- ICRC/HiCri mouse
- Lsc/p115-/- mouse
- Sprouty2-/- mouse
- Rassf1a-/- mouse
- …
Pang J, Borjeson TM, Muthupalani S, et al. Megaesophagus in a Line of Transgenic Rats: A
Model of Achalasia. Veterinary Pathology 2014 ; 51 (6) : 1187-1200.

7. Clinical description
Sinan H, Tatum RP, Soares RV, Martin AV, Pellegrini CA, Oelschlager BK. Prevalence of respiratory
symptoms in patients with achalasia. Dis Esophagus. 2011 ; 24 : 224-228.
Massey BT, Hogan WJ, Dodds WJ, Dantas RO. Alteration of the upper esophageal sphincter belch reflex in
patients with achalasia. Gastroenterology. 1992 ; 103 : 1574-1579.

8. Vigorous achalasia
=
achalasia
+
high-amplitude contractions
Goldenberg SP, Burrell
M, Fette GG, Vos C, Traube
M. Classic and vigorous
achalasia: a comparison of
manometric, radiographic,
and clinical findings.
Gastroenterology 1991 ;
101 (3) : 743-748.
Ghoshal UC, Daschakraborty SB, Singh R. Pathogenesis of achalasia cardia.
World J Gastroenterol 2012 ; 18 (24) : 3050-3057.

9. Diagnosis
History
Esophageal manometry
- conventional
- high-resolution (HRM)
EndoFLIP®
Endoscopy
- upper GI endoscopy
- endoscopic ultrasound (EUS)
Barium swallow study
Chest X-ray
CT chest

10. Esophageal manometry
Vantrappen G, Vangoidsenhoven GE, Verbeke S, Vandenberghe G, Vanderbroucke J. Manometric Studies in
Achalasia of the Cardia, before and after Pneumatic Dilations. Gastroenterology. 1963 ; 45 : 317-325.
Siewert JR, Feussner H. Can a sequential analysis of motor events confirm the existence of motility disorders?
https://www.hon.ch/OESO/books/Vol_4_Prim_Motility/Articles/ART027.HTML

11. Rohof WO, Salvador R, Annese V et al. Outcomes of Treatment for Achalasia Depend on Manometric Subtype. Gastroenterology 2013 ; 144 : 718-725.
Pandolfino JE, Kwiatek MA, Nealis T, Bulsiewicz W, Post J, and Kahrilas PJ. Achalasia: A New Clinically Relevant Classification by High-Resolution
Manometry. Gastroenterology 2008 ; 135 (5) : 1526-1533.

12. WO Rohof, R Salvador, V Annese et al. Outcomes of Treatment for Achalasia Depend on Manometric Subtype. Gastroenterology 2013 ; 144 : 718-725.

13. EndoFLIP®
= Endolumenal Functional Lumen
Imaging Probe
McCoy E, Snape W, Lin MS et al. EndoFLIP in Comparison to High-Resolution Manometry and Eckardt Score in the
Assessment of Achalasia Prior to Intervention. Am J Gastroenterol 2015 ; 110 : S701-702.

14. Endoscopy
Minami H, Isomoto H, Miuma S, Kobayashi Y,
Yamaguchi N, Urabe S, et al. New Endoscopic
Indicator of Esophageal Achalasia: “Pinstripe
Pattern”. PLoS ONE 2015 ; 10 (2) : e0101833.

15. - Biopsies ?
- EUS ?
Sotoudehmanesh R, Mikaeli J, Daneshpajooh M, Modirzadeh A, Mehrabi N. Endoscopic ultrasonography findings in
patients with achalasia. Esophagus 2011 ; 8 : 187.
Rodrigo S, Abboud G, Oh D, DeMeester SR, Hagen J, Lipham J, et al. High intraepithelial eosinophil counts in esophageal
squamous epithelium are not specific for eosinophilic esophagitis in adults. Am J Gastroenterol. 2008 ; 103 : 435-442.
normal
achalasia

16. Barium swallow study
Jafferbhoy S and Rustum Q. Achalasia. N Engl J Med 2012 ; 366 : e15.sigmoid-shaped esophagus
Birgisson S and Richter JE. Achalasia: What’s New in Diagnosis and Treatment? Dig Dis 1997 ; 15 (suppl 1) : 1-27.

17. Timed barium
esophagogram
de Oliveira JM, Birgisson S, Doinoff C, Einstein D, Herts B, Davros W, et al. Timed barium swallow: a simple technique for
evaluating esophageal emptying in patients with achalasia. AJR Am J Roentgenol. 1997 ; 169 : 473-479.

18. Differential diagnosis
Misdiagnosis
= reflux disease with regurgitation
Differential diagnosis
- GERD
- Pseudoachalasia
- malignancies
- secondary achalasia
(prior tight fundoplication)
- Iatrogenic achalasia
obstructive procedures for weight loss
- Eosinophilic esophagitis
- Chagas’ disease
Tumors in the gastric cardia or those
infiltrating the myenteric plexus :
- Adenocarcinoma of the
gastroesophageal junction
- Pancreatic cancer
- Breast cancer
- Lung cancer
- Hepatocellular carcinoma
Tucker HJ, Snape Jr WJ, Cohen S. Achalasia secondary to carcinoma: manometric and clinical features. Ann Intern Med. 1978 ; 89 : 315-318.
de Oliveira RB, Rezende Filho J, Dantas RO, Iazigi N. The spectrum of esophageal motor disorders in Chagas’ disease. Am J Gastroenterol. 1995 ; 90 : 1119-1124.

19. Natural history
Zendehdel K, Nyrén O, Edberg A, and Ye W. Risk of Esophageal Adenocarcinoma in Achalasia Patients, a
Retrospective Cohort Study in Sweden. Am J Gastroenterol 2011 ; 106 : 57-61.
Increased risk of :
- Aspiration pneumonia
- Weight loss
- Malnutrition
Vantrappen G, Hellemans J, Deloof W, Valembois P,
Vandenbroucke J. Treatment of achalasia with pneumatic
dilatations. Gut 1971 ; 12 : 268-275.

20. Treatment
Aims :
- reduce LES pressure
- relieve functional obstruction to
esophageal transit
- facilitate esophageal emptying
Modalities :
- oral pharmacologic agents
- chemical denervation by
endoscopic injection of botulinum
toxin
- pneumatic dilation
- surgical myotomy
- per-oral endoscopic myotomy
(POEM)
- self-expanding metallic stents
- esophagectomy
and nutritional support if necessary
Pharmacologic treatment
Aim
= relaxation of the smooth muscle
 to lower LES pressure
- Calcium channel blockers
- Nitrates
- Anti-cholinergics
- atropine
- dicyclomine
- cimetropium
- Beta-adrenergic agonists
- terbutaline
- Theophylline
Vaezi MF, Richter JE. Current therapies for achalasia: comparison and efficacy. J Clin Gastroenterol. 1998 ; 27 : 21-35.

21. Botulinum toxin treatment
Pasricha PJ, Ravich WJ, Hendrix TR, Sostre S, Jones B, Kalloo AN. Treatment of achalasia with intrasphincteric injection of botulinum toxin. A Pilot Trial. Ann
Intern Med. 1994 ; 121 : 590-591.
Fishman VM, Parkman HP, Schiano TD, Hills C, Dabezies MA, Cohen S, et al. Symptomatic improvement in achalasia after botulinum toxin injection of the
lower esophageal sphincter. Am J Gastroenterol. 1996 ; 91 : 1724-1730.
DA Patel, HP Kim, JS Zifodya and MF Vaezi. Idiopathic (primary) achalasia: a review. Orphanet
Journal of Rare Diseases 2015 ; 10 : 89-102.
PJ Pasricha, R Rai, WJ Ravich, TR
Hendrix and AN Kalloo. Botulinum
Toxin for Achalasia: Long-term
Outcome and Predictors of
Response. Gastroenterology 1996 ;
110 : 1410-1415.
Long-term efficacy = 30%

22. Pneumatic dilation
Eckardt VF, Aignherr C, Bernhard G. Predictors of
outcomes in patients with achalasia treated by
pneumatic dilatation. Gastroenterology 1992 ; 103 :
1732-1738.
Wong RKH. Pneumatic dilation for achalasia. Am J
Gastro 2004 : 578-580.
Hulselmans M, Vanuytsel T, Degreef T, Sifrim D,
Coosemans W, Lerut T, and Tack J. Long-term
Outcome of Pneumatic Dilation in the Treatment of
Achalasia. Clin Gastro Hepatol 2010 ; 8 : 30-35.
5-y remission rate = 40%

23. Predictors of favorable clinical
response :
- older age (>45 years)
- female gender
- narrow esophagus
- LES pressure after dilation of <10
mmHg
- increased emptying on post-
treatment timed barium
esophagram
- type II pattern on HRM
Vaezi MF, Baker ME, Achkar E, Richter JE. Timed barium oesophagram: better predictor of long term
success after pneumatic dilation in achalasia than symptom assessment. Gut 2002 ; 50 : 765-770.
Esophageal perforation ~2%

24. EsoFLIP® dilation catheter
Lenglinger J, Kristo I, Scharitzer M, et al. Lower esophageal sphincter dilation using a balloon incorporating impedance
planimetry imaging (EsoFLIP®): Feasibility and initial experience in the treatment of patients with achalasia.
Gastroenterology 2015 ; 148 (4) : S805.

25. Surgical myotomy
Ali A, Pellegrini CA. Laparoscopic myotomy: technique and efficacy in treating achalasia. Gastrointest Endosc Clin N Am. 2001 ; 11 : 347-358.
Patel DA, Kim HP, Zifodya JS and Vaezi MF. Idiopathic (primary) achalasia: a review. Orphanet Journal of Rare Diseases 2015 ; 10 : 89-102.
Csendes A, Braghetto I, Burdiles P, Korn O, Csendes P, and Henríquez A. Very Late Results of Esophagomyotomy for Patients With Achalasia.
Ann Surg 2006 ; 243 : 196-203.

26. Richards WO, Torquati A, Holzman MD, et al. Heller Myotomy
Versus Heller Myotomy With Dor Fundoplication for Achalasia. A
Prospective Randomized Double-Blind Clinical Trial. Ann Surg
2004 ; 240 : 405-415.
Wei MT, He YZ, Deng XB, Zhang YC, Yang
TH, Jin CW, et al. Is Dor fundoplication
optimum after laparoscopic Heller
myotomy for achalasia? A meta-analysis.
World J Gastroenterol. 2013 ; 19 : 7804-
7812.

27. Per-oral endoscopic
myotomy (POEM)
Pasricha PJ, Hawari R, Ahmed I, Chen J, Cotton PB, Hawes RH, et al. treatment of achalasia. Endoscopy. 2007 ; 39 : 761-764.
Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010 ; 42 : 265-271.
Bechara R, Ikeda H & Inoue H. Peroral endoscopic myotomy: an evolving treatment for achalasia. Nature Reviews Gastroenterology & Hepatology 2015 ; 12 :
410-426.

28. Other modalities
Self-expanding metallic stents (SEMS)
Esophagectomy
Okwara C and Cangemi D. Achalasia with Megaesophagus. N Engl J Med 2015 ; 373 (25): e30.
Duranceau A , Liberman M , Martin J and Ferraro P. End-stage achalasia. Dis Esophagus 2012 ; 25 : 319-330.
Sioulas AD, Malli C, Dimitriadis GD, Triantafyllou K. Self-expandable metal stents for achalasia: Thinking out of the box! World J Gastrointest Endosc
2015 ; 7 (1) : 45-52.

29. PD vs botox
Vaezi MF, Richter JE, Wilcox CM, Schroeder PL, Birgisson S, Slaughter RL, et al. Botulinum toxin versus pneumatic
dilatation in the treatment of achalasia: a randomised trial. Gut 1999 ; 44 : 231-239.

30. PD vs. Heller myotomy
Boeckxstaens GE, Annese V, Bruley des Varannes S, et al. Pneumatic Dilation versus
Laparoscopic Heller’s Myotomy for Idiopathic Achalasia. N Engl J Med 2011 ; 364 : 1807-1816.
Karanicolas PJ, Smith SE, Inculet RI, Malthaner RA, Reynolds RP,
Goeree R, et al. The cost of laparoscopic myotomy versus
pneumatic dilatation for esophageal achalasia. Surg Endosc.
2007 ; 21 : 1198-1206.
Gockel I, Junginger T, Bernhard G, Eckardt VF. Heller myotomy
for failed pneumatic dilation in achalasia: how effective is it?
Ann Surg. 2004 ; 239 : 371-377.

31. Management algorithms
Chuah SK, Chiu CH, Tai WC, Lee JH, Lu HI, Changchien CS, et al. Current
status in the treatment options for esophageal achalasia. World J
Gastroenterol. 2013 ; 19 : 5421-5429.
Francesco Torresan, Alexandros Ioannou, Francesco Azzaroli, Franco
Bazzoli. Treatment of achalasia in the era of high-resolution
manometry. Annals of Gastroenterology 2015 ; 28 : 1-8.

32. Patient follow-up
assessment of symptom relief
barium esophagogram ?
endoscopy ?

33. Take home messages
- Rare disease
- Complex pathophysiology
- Main symptom = dysphagia
- Diagnosis = esophageal
manometry
(HRM > conventional)
- Always upper GI endoscopy
- Pseudo-achalasia !
- Treatment
- Pneumatic dilation
- Heller’s myotomy
- Ongoing research
any question ?