Primary Achalasia : POEM Vs Heller's Myotomy AMOL BAPAYE MD (MS ), FAS GE

SHIVANAND DESAI CENT ER FOR DIG EST IVE DISOR DER S

DEENANAT H MANG ESHKAR HOSPITAL & R ESEAR CH CENT ER , PUNE, INDIA

What is Achalasia Cardia? Benign progressive disorder characterized by loss of esophageal motility & non relaxation of LES on wet swallows Therapy aims at –

Disruption / relaxation of circular muscle fibers at LES No method devised to improve esophageal body motility

Therapeutic options –

Pharmacotherapy Endoscopic balloon dilatation Endoscopic Botox injection Laparoscopic Heller’s myotomy (LHM) Per-oral endoscopic myotomy (POEM)

What Is POEM?

Pre POEM Post POEM

1 Minute

2 Minute

Is POEM effective?

POEM : A Series of 500 Patients

3 yr or more follow up – 61 pts

Eckardt score - 1

Post-operative LES - 11.7 mm Hg

Overall success rate was - 88.5%

Inoue H et al. 2015 Sigmoid Esophagus

Failed LHM/ Endoscopic

POEM Efficacy

Weighted results for published series

Mean follow up of 6 months (1-13 months)

Stavropoulos et al , Ther Adv Gastroenterol 2013

Continent N Mean Age Mean Length (cm)

Eckardt Score Pre/Post

LES pressure Pre/Post (mmHg)

Efficacy

ASIA 374 45 13.5 6.33/1.19 32.5/4.9 97.9%

NORTH AMERICA

107 50.4 9.1 7.4/0.3 38.6/14.3 95.3%

EUROPE 128 43.5 12.4 7.1/1.0 34.1/12.5 88.6%

Is POEM effective?

POEM efficacy >90%

Long-term outcomes of per-oral endoscopic myotomy in achalasia patients with a minimum follow-up of 2 years: an international multicenter study Saowanee Ngamruengphong1, Haruhiro Inoue2, Philip Chiu3, Hon-Chi Yip3, Amol Bapaye4, Michael Ujiki5, et al. GIE 2016 (accepted for publication)

• N = 205, prior therapy = 81 (39.5%)

• Median follow up = 31 months (IQR 26 – 38)

• Clinical success = 98% (185/189), 98% (142/144), & 91% (187/205) at 6, 12 & ≥24-months

• 185 patients with clinical response @ 6-months – recurrent symptoms @ 2-years = 11 (6%)

• Prior PBD associated with long-term Rx failure (OR, 3.41; 95% CI, 1.25 – 9.23)

• Procedure related AE = 8.2%

• Abnormal esophageal acid exposure and GERD = 37.5% and 18%

Conclusions

POEM is safe and provides high initial clinical success and excellent long-term outcomes

• Recurrence of achalasia after LHM – 20% • Commonest cause is incomplete myotomy

LHM although a gold standard for many years, IS NOT the IDEAL procedure for achalasia

Safety and outcomes of laparoscopic re-operation for achalasia

Zaninotto G Ann Surg 2002; 235: 186 – 192

Is LHM Ideal ?

Overall complications – ◦ 59 / 1237 (4.8%) – major – 2.8%, deaths – 4

Intra-operative mucosal injury – ◦ 4% (not recorded as complication)

Readmissions – 3.1%, reoperations – 2.3%

LOS – 2.8d +/- 5.5d

Advanced age, co-morbid illness associated with increased operating time, complications & LOS

National outcomes of laparoscopic LHM: Operative complications and risk factors for adverse events.

Is LHM Ideal ?

Ross SW Surgical endoscopy 2015

Reasons and prevalence of reoperations after esophagomyotomy for achalasia.

• 18% re-interventions due to failure or complications • 9% repeat operations due to incomplete myotomy

Conclusions – • Early reoperations due to technical errors (mucosal injury) • Late reoperations due to recurrence (incomplete myotomy)

Is LHM Ideal ?

Li J Surg Laparosc Endosc Percutan Tech. 2012 Oct;22(5):392-5 .

POEM Vs LHM Seven Studies POEM (n) LHM (n) Type

Bhayani et al, 2014 37 64 Prospective

Vigneswaran et al, 2014 5 3 Retrospective

Hungness et al, 2014 18 55 Retrospective

Tietelbaum et al, 2013 12 17 Prospective

Ujiki et al, 2013 18 21 Prospective

Kumagai et al, 2015 42 41 Prospective

Chan et al, 2015 33 23 Retrospective

Last two studies have not been included in any of the published meta-analyses

POEM Vs LHM

Two Abstracts POEM n

LHM n

Type of Comparison

Renteln V et al, 2013 70 110 Prospective

Kumbhari et al, 2015 52 52 Retrospective

Von Renteln D, Fockens P et al. Gastrointest. Endosc. 2013; 77 (Supp 5): AB122.

Kumbhari V et al. Gastrointes. Endosc. 2015; 81 (Supp 5): AB492.

Studies Comparing POEM Vs LHM

Efficacy

Complications

a. Operative time

b. Hospital stay

Follow up

Bhayani et al Equal Both Less in POEM 6 months

Vigneswaran et al Equal - 5 months

Hungness et al Equal a. Less in POEM

b. Similar

6 months

Tietelbaum et al Equal improvement in EGJ distensibility (FLIP)

Ujiki et al Equal Equal in both 116/ 164 days

Studies Comparing POEM Vs LHM

Efficacy Complications

a.Operative time b.Hospital stay

Follow up

Kumagai et al Equal a.Less in POEM b.Equal

3 months

Chan et al Equal a. Less in POEM b. Equal

6 months

Renteln V et al* Equal a. - b. -

3 months

Kumbhari et al** Equal a. Less in POEM b. Equal

4.3 months

*POEM - lower 3 month Eckhardt scores (1 vs. 1.4,p=0.05), lower post-op LESP (9 vs.12 mmHg, p=0.01) **POEM - less cost ($14,481 vs. $17,782)

All Studies

Equal Efficacy

Similar adverse events

Differences

– Operative time

- Pain/ Blood loss

- Hospital stay

- Early resumption to work

- Less cost

Meta-analyses - POEM Vs LHM

Four Meta-analyses Studies

Total (Comparative)

Talukdar et al, 2014 19 (5)

Patel et al, 2015 22 (3)

Wei et al, 2015 4

Zhang et al, 2016 4

Meta-analyses - POEM Vs LHM Meta-analysis Main Outcome Studies

Total (Comparative)

Talukdar et al, 2014 Equal efficacy, pain, reflux, adverse events 19 (5)

Patel et al, 2015 Similar adverse events, perforation, operative time 22 (3)

Wei et al, 2015 Comparable complications and recurrence 4

Zhang et al, 2016 Equal efficacy, safety, stay and operation time 4

All Meta-analyses

Equal Efficacy

Similar adverse events

Differences – Operative time

Redo LHM compared to primary LHM •More complications due to scarring and fibrosis due to previous intervention

•Redo Heller: • More conversion to open (up to 7%)

• Longer procedure time

• Lower efficacy • More postoperative complications: gastrointestinal perforations (1.5% to 20%),

pneumothorax (1.9% to 6.7%), pulmonary complications (1.3% to 4% of patients)

Wang L, Li YM, World J Gastroenterol 2008; 14:7122e7126

Rosemurgy AS, J Am Coll Surg. 2010 May;210(5):637– 45, 645–7

Lynch KL, Am J Gastroenterol, 107(12):1817-25

James, D. R. Minim Invasive Ther Allied Technol 2012, 21 (3), 161-7

Author (year) Type Sample size Control/Cohorts

Previous intervention

Follow up (months)

Outcome

Onimaru (2013) Prospective 10 (11)/ 315 (total)

All post Heller➡ ️PBD failure

18.3 (3-13) Feasibility Procedure time Difficulty Efficacy: • Symptom relief • Eckardt Score

improvement • LES pressure

reduction Complications GERD QOL Meds used prior & after POEM

Sharata (2013) Retrospective I: 12 NI: 28

Bo: 10 PBD: 2

6

Zhou (2013) Prospective 12 All failed Heller 10.4 ± 3.1

Vigneswaran (2014)

8 (all post Heller) (POEM:5 Heller:3)

All post Heller POEM: Bo 2, PBD 4, Fundopl 3 Heller: Bo 1, PBD 2, Fundopl 2

5

Ornstein (2014) Retrospective, Prospective database

I:16 NI:24

BO 9, PBD 9, HM 3, Fundopl2

10

Ling (2014) Prospective PBD: 21 NI: 30

All PBD failure 1 yr (I)/1.2+0.2 yr (NI)

Jones (2015) Prospective database

I: 15 NI: 25

BO 7, PBD 5, HM 3 10 (5-17)

• POEM post intervention is effective in reduction of symptoms, dysphagia score,

LES pressure with acceptable complication rate in short/medium follow up

• Comparable to data when performed without prior intervention

• POEM in post intervention setting is associated with QOL improvement

Advantages of POEM over LHM

1. Direct visual recognition of the submucosal layer, less perforations

2. POEM is submucosal, doesn’t alter surrounding anatomy; possible less reflux, less severe reflux; further treatment options are safer

3. Less chances of fusion of the myotomy line in view of lateral dissection post POEM

Comparative Evaluation of Per Oral Endoscopic Myotomy (POEM) for the Treatment of Achalasia in Patients With Failed Heller Myotomy vs Patients Without a History of Surgical Myotomy: A Multicenter Retrospective Cohort Study Saowanee Ngamruengphong, Haruhiro Inoue, Michael Ujiki, Amol Bapaye , Pankaj N. Desai , Thierry Ponchon, et al GIE 2016 (Abstract)

• N = 181 (91 prior HM, 90 controls), 11 centers (4 US, 4 Europe, 3 Asia)

• Controls matched for age, achalasia subtype & Eckhardt scores

• Clinical response defined as post POEM Eckhardt scores <= 3

• Technical success, clinical success & AE’s compared between two groups

• Mean follow up = 8.5 months (IQR 3.2 – 14.7)

• Technical success comparable – 89/91 (98%) vs 100% (p=0.49)

• Procedure times – similar

• Adverse events comparable – 7 (8%) vs 12 (13%) (p=0.23)

Comparative Evaluation of Per Oral Endoscopic Myotomy (POEM) for the Treatment of Achalasia in Patients With Failed Heller Myotomy vs Patients Without a History of Surgical Myotomy: A Multicenter Retrospective Cohort Study Saowanee Ngamruengphong, Haruhiro Inoue, Michael Ujiki, Amol Bapaye , Pankaj N. Desai , Thierry Ponchon, et al GIE 2016 (Abstract)

• Clinical response – significantly lower in HM group – 80% vs 94% (p=0.02)

• Mean post POEM Eckhardt scores higher in HM group - 2.09 +/- 2.5 vs 1.08 +/- 1.2 (p=0.002)

• Univariate analysis – prior HM (OR 3.54, p 0.02) & prior PD (OR 3.36, p 0.01) were significantly associated with clinical failure

• Multivariate analysis – prior HM (adjusted OR 2.91, p 0.05) was marginally associated with clinical failure after POEM Conclusions

Although rate of clinical success in patients with prior HM is lower than those without, safety profile of POEM is comparable in both groups

Type III Achalasia/ SED’s: Tailor-made myotomy according to requirement / indication

Long segment LES

Spastic contractions in lower third esophagus

Rarest amongst all AC types

Most difficult to treat

Part of SED’s – DES, Jackhammer esophagus

Results of Rx for AC according to type

POEM for Type III AC Khashab et al GIE 2015

◦ The only multicenter retrospective study

◦ N = 73, Includes all SED’s ◦ Type III AC = 54

◦ DES = 9

◦ Jackhammer = 10

◦ Outcome measure – Eckhardt score < / = 3

◦ Mean length of myotomy – 16cm (6 – 26)

◦ Duration of procedure – 118min (43 – 345)

POEM for Type III AC

Khashab et al GIE 2015

◦ Success = 93% (overall) ◦ Type III AC = 96.3%

◦ DES = 100%

◦ Jackhammer = 70%

◦ Relief of chest pain – 87%

◦ Reduction in Eckhardt score – ◦ Overall 6.73 to 1.13 (p < 0.01)

◦ Type III AC 6.4 to 0.86 (p < 0.01)

◦ AE = 8 / 73 (11%)

POEM vs. LHM for Type III AC Kumbhari et al EIO 2015

◦ The only retrospective comparative study

◦ Multicenter

◦ N = 75

◦ POEM – 49 (multicenter)

◦ LHM + Dor / Toupet – 26 (single center)

◦ Primary outcome – symptom improvement & decrease in Eckhardt score ≤1

◦ Secondary outcomes – myotomy length, procedure duration, hospital stay,

rate of AE

POEM vs. LHM for Type III AC

Kumbhari et al EIO 2015

◦ Clinical response – 98 vs. 80.8% (p < 0.01)

◦ Mean procedure time – 102 vs. 264min (p < 0.01)

◦ Myotomy length = 16 vs. 8cm (p < 0.01)

◦ AE = 6 vs. 27% (p < 0.01)

◦ Hospital stay = 3.3 vs. 3.2days (p = 0.68)

◦ Post procedure PPI = 38.8 vs. 46.1% (p = 0.7)

Sigmoid Achalasia POEM feasible, effective for sigmoid type (both S1 / S2) including advanced sigmoid achalasia (not amenable to LHM)

Inoue Endoscopy 2010, Hu JW Surg endosc 2015, Eleftheriadis N Ann Gastroenterol 2014

POEM & GERD

Chuah SK 2013 Cumulative Results of LHM Bhayani NH Annals of surgery 2014; 259: 1098-1103

Inoue H Japanese Journal of clinical medicine 2010; 68: 1749-1752 Bapaye et al J Gastroenterol Hepatol 2014 (Abstract)

POEM has less or similar reflux / less severe reflux (12 – 35%)

Why GERD is a Problem in LHM: Hiatal dissection & post-op GERD

Parameter Heller - Dor + Complete HD

Heller - Dor + limited HD

Heller only + limited HD

P-value

Median resting LES pressures Low High High < 0.001

Median acid exposure time High Low Low < 0.001

Abnormal De Meester @ 3-yrs 23.1% 8.5% 9.1% < 0.001

Prospective, randomized 3-yrs follow up – 84 pts of LHM

Conclusion – Limited HD achieves better post op GERD control

No Hiatal Dissection in POEM ! Simic AP. J Gastrointest Surg 2010

Advantages of POEM: Summary

PD VS LHM

Graded or ‘on demand’ dilatation is equal to LHM in type I And Type II AC

LHM better than Single dilatation

PD VS POEM

No comparative data

Individualized treatment

PD LHM POEM

TYPE I AC 63-65% 81% 91.4%

TYPE II AC 90-93% 93-100% 93.6%

TYPE III AC 33-40% 80-86% 98%

Overall efficacy 44-84% 57-89.3% 80-97%

Follow up > 5 years > 5 years

1-3 Years

GER 4% 9-33% 15-30%

Zaheer, Reddy DN, Ramchandani M, J Gastrointest Dig Syst 2016

Summary of available data

LHM > Single Pneumatic dilatation

LHM = Graded Dilatation (Type I, II)

POEM = LHM

POEM >= LHM (Type III, spastic disorders)

POEM vs PD – No literature

POEM Should it be the first line of treatment ?

Yes • If I am in a institute where expertise is available • If my patient is non compliant for repeated dilatation • If patient desires minimally invasive & one time treatment • If patient has type III achalasia

No • If patient has type II / type I achalasia & is willing for

repeated dilatation (PBD) • Severe sigmoidization – Esophagectomy

Thank You !