1. The New Era of Esophageal Motility Disorders
Joint Hospital Surgical Ground Round
April 2014
Hwang Wan Wui Winston
Queen Elizabeth Hospital

2. Presentation Outline Chicago Classification Scheme Achalasia
High Resolution Esophageal Pressure Topography
Achalasia
Presentation
Investigation
Treatment

3. Chicago Classification Scheme Achalasia
High Resolution Esophageal Pressure Topography
Achalasia
Presentation
Investigation
Treatment

4. The Chicago Classification
Investigators in the Northwestern University in Chicago developed a new classification scheme to facilitate the diagnosis of esophageal motility disorders by interpretation of high resolution esophageal pressure topography (EPT)
Esophageal pressure topography is a combination of high resolution manometry (HRM) and pressure topography
The latest iteration of the Chicago Classification came after the High Resolution Manometry Working Group met in Switzerland in 2011

5. Esophageal Pressure Topography V.S. Conventional Manometry
Esophageal Pressure Topography (EPT)
Conventional Manometry (CM)
Sensors
Closely spaced pressure sensors, 1cm apart
8 sensors: 4 in esophageal body & 4 at level of GEJ. Pressure sensors 3-5cm apart
Swallows
Series of 10 test swallows of 5ml water each
Position
Supine position
Advantage
Results shown as topographic pressure reading over time
Allow detection of more subtle differences
EPT plots, known as Clouse plots, are generated by computer software during 10 wet (5ml water) swallows, and there is no need to perform different steps in the evaluation because all variables can be assessed during the single swallows.
No pull-through technique is required because the catheter can record pressure from stomach to the oropharynx

6. The Chicago Classification
EPT Metrics
Metric
Description
IRP
Integrated Relaxation Pressure
Mean of the lowest EGJ pressure over 4 seconds measured in the ten-second window after deglutitive UES relaxation
DCI
Distal Contractile Integral
Volume (amplitude x duration x length) from proximal to distal pressure troughs
CDP
Contractile Deceleration Point
Transition from peristaltic propagation to late phase of esophageal emptying (proceeds much more slowly)
CFV
Contractile Front Velocity
Slope between the proximal pressure troughs and CDP DL
Distal Latency
Interval between UES relaxation and the CDP, duration of peristalsis
Peristaltic Breaks
Gaps of the peristaltic contraction between the UES and EGJ
IRP
Integrated Relaxation Pressure
Diagnosis of esophageal motility disordersare based on these EPT specific metrics and criteria
All pressures referenced to atmospheric pressure except the integrated relaxation pressure (IRP), which is referenced to gastric pressure
For DCI: to exclude the effects of intrabolus pressure, the first 20mmHg is ignored
Each metric developed to characterize a specific feature of deglutitive esophageal function

7. Esophageal Pressure Topography V.S. Conventional Manometry
Esophageal Motility Characteristic
EPT CM
LES Relaxation
1. Integrated Relaxation Pressure (IRP)
<15mmHg
1. LES relaxation
<8mmHg more than gastric pressure
Peristaltic Propagation
2. Contractile Deceleration Point (CDP)
No corresponding
3. Contractile Front Velocity (CFV)
2. Wave progression between pressure sensors 8 and 3 cm above the LES
4. Distal Latency (DL)
Contractile Vigor
5. Distal contractile Integral (DCI)
3. Peristaltic amplitude
EPT allows more sophisticated interpretation of esophageal motility

8. The Chicago Classification
Achalasia
Type I: Classic
Type II: Pan-esophageal pressurization
Type III: Spastic
Achalasia
Type I: Classic
Type II: Pan-esophageal pressurization
Type III: Spastic
IRP >= upper limit of normal AND absent peristalsis
IRP >= upper limit of normal AND absent peristalsis
YES NO
IRP >= upper limit of normal AND some instances of intact or weak peristalsis
IRP >= upper limit of normal AND some instances of intact or weak peristalsis
YES
EGJ Outflow Obstruction
Achalasia variant
Mechanical obstruction
EGJ Outflow Obstruction
Achalasia variant
Mechanical obstruction
Analysis of an EPT study is performed stepwise that first defines patients based on EGJ relaxation pressures and subsequently uses individual swallow patterns defined by EPT metrics to further subclassify patients into specific categories
Assessment of EGJ pressure morphology at baseline
Describes pressure morphology of the EGJ to determine whether a hiatus hernia is present and where the pressure inversion point is located. Baseline end-expiratory pressure and inspiratory augmentation are recorded to assess integrity of the crural diaphragm as an extrinsic sphincter
2. Assessment of EGJ relaxation and bolus pressure dynamics through the EGJ. The IRP has replaced the conventional measures of nadir or end-expiratory LES relaxation pressure on CM because EPT eveluation of the pressure was heavily reliant on intrabolus pressure nad was not a pure measure of LES relaxation.
The IRP is the lowest mean EGJ pressure for 4 contiguous or noncontiguous seconds during the deglutitive period.
The IRP is a complex metric as it involves accurately localizing the margins of the EGJ, demarcating the time window following deglutitive upper sphincter relaxation within which to anticipate EGJ relaxation to occur, applying an e-sleeve measurement within that 10 s time box (Fig. 1) and then finding the 4 s during which the e-sleeve value was least. The IRP is the mean pressure during those 4 s, necessarily being influenced not only by LES relaxation, but also by crural diaphragm contraction and intrabolus pressure (i.e. outflow obstruction) in the post-deglutitive period.
3. Assess integrity of the peristaltic wave
To determine if peristaltic activity is intact, failed or associated with small (2-5cm) or large (>5cm) peristaltic breaks in the 20mmHg isobaric contour.
4. Determine the contractile deceleration point
This promotes emptying of the remaining bolus
This landmark is in close proximity to the proximal border of the LES NO
IRP is normal BUT abnormalities in other metrics
IRP is normal BUT abnormalities in other metrics
YES
Other Esophageal Motility Disorders
Distal esophageal spasm
Hypercontractile esophagus
Absent peristalsis
Nutcracker esophagus
Other Esophageal Motility Disorders
Distal esophageal spasm
Hypercontractile esophagus
Absent peristalsis
Nutcracker esophagus

9. Chicago Classification Scheme Achalasia
High Resolution Esophageal Pressure Topography
Achalasia
Presentation
Investigation
Treatment

10. Achalasia - Presentation
Dysphagia
both liquid and solid
Regurgitation
Chest pain
Cough
Aspiration pneumonia
Weight loss

11. Achalasia - Investigations
Barium Esophagogram
Classical “bird’s beak” appearance
Dilated esophageal body
High Resolution Manometry
Esophagogastroduodenoscopy
Rule out pseudoachalasia
Most common cause is malignancy infiltrating the EGJ
Timed barium swallow: test individualized for each patient and primarily assesses esophageal emptying of barium in the upright position over 5 minutes
Manometry is required to establish the diagnosis of achalasia and must be done in any patient where invasive treatments such as pneumatic dilatation or surgical myotomy are planned

12. Achalasia – Type I (Classic Achalasia)
Type I tend to present with more severe esophageal dilatation and they may represent disease progression from Type II with esophageal body decompensation after prolonged outlet obstruction. Therefore chest pain less common in type I than II or III.
Type I (classic achalasia) - there is no significant pressurization within the esophageal body (all dark blue) and impaired lower esophageal sphincter (LES) relaxation (IRP = 42 mmHg).
Mean IRP >= upper limit of normal (IRP =42mmHg)
100% failed peristalsis

13. Achalasia – Type II Mean IRP >= upper limit of normal
Type II patients have aperistalsis but preserved muscularis propria longitudinal muscle contraction and sufficient excitation fo the circular muscle to generate substantial intrabolus pressure in the esophageal body. Therefore, they respond very well to any therapy that reduced the functional obstruction at the EGJ e.g. botox, PD or LHM.
Type II patientshas functional obstruction of distal esophagus involving not only the EGJ but also the distal smooth muscle segment (complete obliteration). Clinically, type III very similar to distal esophageal spasm which has few good treatment.
Mean IRP >= upper limit of normal
No normal peristalsis
Panesophageal pressurization with >20% of swallows, which may exceed LES pressure, causing the esophagus to empty

14. Achalasia – Type III (Spastic Achalasia)
Mean IRP >= upper limit of normal
No normal peristalsis
Fragments of premature (spastic) distal contractions with 20% of swallows
Although this is also associated with rapidly propagated pressurization, the pressurization is attributable to an abnormal lumen obliterating contraction

15. Achalasia Treatment Pharmacological
Calcium channel blockers and nitrates
short lived response
side effects: headache, dizziness and pedal edema
Botulin toxin injection
prevents the release of acetylcholine at terminal nerve endings
results last 6-9 months. [1]
Pharmacological therapies are less effective than endoscopic or surgical therapies
Can be used to treat patients with high surgical risks e.g. elderly and comorbidities
sildenafil, a phos- phodiesterase inhibitor that reduces the breakdown of cyclic guanosine monophosphate, the second messenger mediating NO in- duced relaxation
Sildenafil, phosphodiesterase inhibitor
Botulin toxin: Repeated injections affects dissection of the submucosal plane during Heller’s myotomy and lead to mucosal perforation
[1] Pasricha PJ, Ravich WJ, Hendrix TR, Sostre S, Jones B, Kal- loo AN. Intrasphincteric botulinum toxin for the treatment of achalasia. N Engl J Med 1995; 332:

16. Achalasia Treatment Pneumatic Dilation
Aims at disrupting the LES by forceful dilation using air filled balloons
Many use a graded dilation protocol starting with 3.0 cm, then stepping up to 3.5cm and 4.0cm
The procedure is done during endoscopy, with the balloon placed over the guidewire and positioned across the LES

17. Achalasia Treatment Pneumatic Dilation
Promising short term results
Long term follow-up showed recurrence
Author, Journal
Study Design N
No. of PD
Results
Eckardt VF, et al
Gut 2004 [1]
Prospective cohort 54 1
5 year remission rate 40%
10 year remission rate 36%
Katsinelos P, et al
World J Gastroenterol 2005 [2] 39
1-3
5 year remission 78%
10 year remission 61%
15 year remission 58.3%
standardized with the development of the Rigiflex balloon system (Boston Scientific Corporation, MA, USA). These are noncompliant polyethylene balloons available in 3 di- ameters (3.0, 3.5 and 4.0 cm), on a flexible catheter that can be placed over a guidewire at endoscopy.
[1] Eckardt VF, Gockel I, Bernhard G. Pneumatic dilation for achalasia: late results of a prospective follow up investigation. Gut 2004; 53:
[2] Katsinelos P, Kountouras J, Paroutoglou G, Beltsis A, Zavos C, Papaziogas B, Mimidis K (2005) Long-term results of pneu- matic dilation for achalasia: a 15 years’ experience. World J Gastroenterol 11:5701–5705

18. Achalasia Treatment Laparoscopic Heller’s Myotomy (LHM)
Myotomy from 1.5-3cm distal to the EGJ dividing the longitudinal and oblique muscle to 6-8cm proximal to the EGJ dividing longitudinal and circular muscle of esophagus
Partial fundoplication is routinely performed as incidence of reflux after Heller’s myotomy is >50%
Initially through thoracotomy but because unpopular due to high morbidity
Became popular again after laparoscopic approach was introduced

19. Achalasia Treatment Laparoscopic Heller’s Myotomy (LHM)
LHM considered superior to pneumatic dilation and the first choice of treatment for achalasia
Prospective trials have shown promising long term results of LHM
A prospective trial in Italy followed up 6 years after laparoscopic Heller-Dor operation [1]
Primary outcome was therapeutic success in terms of symptoms improvement
At 6 years, 81.7% of patients still have significant improvement in their symptoms
The option of PD and LHM is an ongoing debate but generally LHM is accepted for young <40-45 male and those with pulmonary symptoms who fail to respond to one or two initial dilatations
LMH esp. for young male patients
Long-term outcome of LHM was only slightly affected by the length of the follow-up and most of the symptomatic failures occurred in the early post-operative period
[1] Costantini M, Zaninotto G, Guirroli E, et al. The laparoscopic Heller-Dor operation remains an effective treatment for esophageal achalasia at a minimum 6-year follow-up. Surg Endosc 2005;19:345-51

20. Achalasia Treatment Laparoscopic Heller’s Myotomy (LHM)
Multicenter RCT published by European Achalasia Trial group in [1]
Primary outcome was therapeutic success, measured by Eckardt score
After 2 years of follow up, the study concluded LHM was not superior to pneumatic dilation
Limitations:
2 year cohort study with no evidence on intermediate and long-term remission rates
All patients in the PD group received 2 to 3 sessions of redilation
Success rates reported in the literature vary widely depending on the criteria used to define success. In particular, if efficacy is defined as the lack of need for any subsequent intervention,15 the success rate with pneumatic dilation is much lower than that with surgery. The use of repeated dilations to treat recurrent symptoms is, however, a generally accepted strategy in clinical practice and leads to excellent control of symptoms, even during long-term follow-up In line with these studies, we allowed patients who were randomly assigned to pneumatic dilation to undergo addi- tional pneumatic dilations if symptoms recurred. The number of pneumatic dilations was limited to a maximum of three series of dilations, each comprising up to two or three dilation proce- dures, but the third and final series was allowed only if it took place more than 2 years after the second series.
[1] Boeckxstaens GE, Annese V, des Varannes SB, Chaussade S, Costantini M, Cuttitta A, Elizalde JI, Fumagalli U, Gaudric M, Rohof WO, Smout AJ, Tack J, Zwinderman AH, Zaninotto G, Busch OR. Pneumatic dilation versus laparoscopic Heller’ s myotomy for idiopathic achalasia. N Engl J Med 2011; 364:

21. Achalasia Treatment in Different Subtypes
Author
Journal
Study Type N
Follow up
Results
Pandolfino JE, et al
Gastroenterology 2008 [1]
Retrospective cohort
213
3 years
Type II achalasia more likely to respond to any therapy
Type II (Botox 71%, pneumatic dilation 91%, Heller’s myotomy 100%)
Type I (56% overall)
Type III (29% overall)
Salvador R, et al
J Gastrointest. Surg
2010 [2]
Prospective cohort
246
31months
- Treatment failure rates:
Type I 14.6%; Type II 4.7% ; Type III 30.4%
- Type II and LES resting pressure >30mmHg were independent predictors of positive outcome
Rohof WO, et al
Gastroenterology 2013 [3]
Multicenter RCT
176
2 years
Treatment success rates:
Type I 81%; Type II 96%; Type III 66%
Type II: success rate for PD was significantly higher than LHM
[1] Pandolfino JE, Kwiatek MA, Nealis T, Bulsiewicz W, Post J, Kahrilas PJ. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008;135:
[2] Salvador R, Costantini M, Zaninotto G, et al. The preoperative manometric pattern predicts the outcome of surgical treatment for esophageal achalasia. J Gastrointest Surg 2010;14:1635–1645
[3] Rohof WO, Salvador R, Annese V, et al. Outcomes of treatment for achalasia depend on manometric subtype. Gastroenterology 2013; 144:718–725

22. Peroral Endoscopic Myotomy (POEM)
Dissection of inner circular muscle layer of the esophagus
Dissection begins around 7cm proximal to EGJ and down to 2cm distal to EGJ
Good short-term results
Long-term results not available yet
Long-term follow-up results are required
Can perform deeper myotomy incisions in the thoracic esophagus than that done in surgical myotomy
Less chance of damaging vagus nerve

23. Conclusion
Pharmacological therapies are not recommended unless patient is not fit for endoscopic or surgical therapies
Pneumatic dilation is the most effective nonsurgical treatment with promising short term results but high recurrence rate in the long term
Laparoscopic Heller’s myotomy should be advocated for patients fit for surgery
The Chicago Classification Scheme is providing a better classification for esophageal motility disorders. It has great impact on how we approach esophageal motility disorders, predict treatment outcomes and choose treatment options

24. The New Era of Esophageal Motility Disorders
Winston Hwang
Queen Elizabeth Hospital

25. References
Goldblum JR, Rice TW, Richter JE. Histopathologic features in esophagomyotomy specimens from patients with achala- sia. Gastroenterology 1996; 111:
Richter JE. Achalasia – An Update. J Neurogastroenterol Motil. Jul 2010; 16(3): 232–242
Boeckxstaens GE, etal. Achalasia. Lancet 2014; 383: 83-93
Stefanidis D, et al. SAGES guidelines of the surgical treatment of esophageal achalasia. Surg Endosc 2012; 26: