Treatment of Achalasia. Dr. Javad Mikaeli Professor of medicine Digestive Disease Research Center Tehran University of medical sciences

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1 Treatment f Achalasia Dr. Javad Mikaeli Prfessr f medicine Digestive Disease Research Center Tehran University f medical sciences

2 Treatment f Achalasia There is n cure fr the disease Treatment is fcused n palliating symptms by decreasing LES pressure: 1-Mechanical disruptin f the muscle fibers f the LES 2-Bichemical reductin in LES pressure

3 Treatment ptins fr Achalasia Medical therapy Pneumatic dilatatin Cardimytmy Btulinum txin injectin Ethanlamine injectin Cmbined methds

4 Treatment f Achalasia Early recgnitin f achalasia ffers the best chances fr an adequate treatment and preventin f cmplicatins such as weight lss and dilatin f the esphagus. Severe esphageal dilatin significantly reduced the respnse t treatment (OR 0.2 cmpared with n dilatin).

5 Images in clinical medicine

6 Achalasia Smth- Muscle Relaxants The drugs are taken sublingually 10 t 30 minutes befre meals. Side effects are headache and hyptensin fr nitrates and peripheral edema fr calcium channel blckers.

7 Achalasia Smth- Muscle Relaxants The efficacy f nifedipine ranged frm 50 t 90%, with side effects seen in up t 30% f patients. Pharmactherapy is frequently assciated with tachyphylaxis.

8 BOTULINUM TOXIN BTX reduce the LES pressure by selectively blcking the release f acetylchline frm chlinergic nerves in the myenteric plexus

9 Btulinum Txin Injectin A respnse t BT supprts the diagnsis f achalasia if the diagnsis is uncertain based upn manmetry. Imprvement in symptms is usually bserved after 24 hurs; peak effects ccur later in sme patients.

10 Achalasia Btulinum Txin Injectin The verall efficacy: 65 t 90% after ne injectin Relapse rates: >50% within 6 t 12 mnths Symptm relief : 75% with repeat injectins during 2 years fllw-up

11 Achalasia Btulinum Txin Injectin Indicatins: Sigmid esphagus Severely malnurished patients Advanced cardipulmnary diseases Epiphrenic diverticula patient s will

12 ACHALASIA (BT) Predictrs f gd respnse Age>50 years Vigrus achalasia (type 2) The 100 X 2 IU btx regimen at fur weeks interval Annese has reprted remissin rate f 68% at 2 years with this regimen.

13 INFLUENCE OF ACHALASIA SUBTYPES Cmpared with type I patients, type II patients were much mre likely t respnd t any kind f therapy (OR 11.2), whereas patients with type III were much less likely t respnd t any therapy (OR 0.24). Mytmy may nly be advantageus in type I patients.

14 Btulinum Txin Injectin Cmplicatins : Transient chest pain (25%) Transient heartburn (5%) GERD (<5%) Antibdies t BT have been detected in patients wh were secndary treatment failures.

15 Surgery after BT r PD Wuld prir BT r PD cause sme degree f difficulty during surgery? As a better explanatin, there may be a subset f patients that is refractry t all frms f treatment, including mytmy.

16 PD versus BT injectin Five trials cmpared PD with BT in patients fllwed fr at least 12 mnths. PD was assciated with a significantly Higher remissin rate Lwer relapse rate Lnger time t relapse

17 RCT cmparing BT t PD The 1 year remissin rate: Single PD (53%) Single BT (15%) (P<0.01) Redilatin (100%) Reinjectin (60%) (P<0.01)

18 Achalasia PD versus BT PD and BT have similar efficacy during shrt-term fllw-up. Repeated therapy with BT is necessary t maintain efficacy.

19 Achalasia Pneumatic dilatin Gd t excellent shrt-term results : 60 t 85% with a single PD Success rates will be declined with time (68% at 12 mnths and 58% after 36 mnths). Repeated dilatins using an "n demand" apprach lead t remissin in the majrity f patients (> 90% at 10 years).

20 Achalasia Graded Pneumatic dilatin The mst ppular pneumatic dilatr is the Rigiflex balln. (Bstn Scientific Crp, Bstn, MA) The smallest size balln (3.0 cm) is typically used fr the first sessin. If symptms persist, the prcedure can be repeated with incrementally larger ballns. "graded apprach"

21 PD- the "prgressive" methd A series f prgressively larger dilatins n the same r successive days until "satisfactry" manmetric and/r radigraphic criteria are met. A retrspective study f 209 patients fund that the respnse t a single series f dilatins was 66 percent at six years.

22 DILATION OF THE LOWER ESOPHAGEAL SPHINCTER Esphageal dilatin with a sft, tapered dilatr (bugienage) is usually prvides nly temprary and incmplete relief f symptms. It is an ptin in patients wh are pr surgical candidates because it has a lwer risk f perfratin cmpared with PD.

23 Achalasia Pneumatic dilatin We evaluate patients within ne mnth after each prcedure by symptm scre and timed barium esphaggram The degrees f patient symptm imprvement and the esphageal emptying in esphaggram were nt always crrelatrd.

24 Timed Barium Esphaggram

25 Timed Barium Esphaggram

26 Timed Esphaggram minute Height Vlume

27 Achalasia Pneumatic dilatin Mst relapses and need fr a secnd PD ccur in the first 12 mnths. 25 t 50 percent f patients relapsing ver a five year perid. Thse wh stay well in the first five years r s are likely t cntinue t d well.

28 Achalasia Pneumatic dilatin PD may nt be equally effective fr relieving all symptms. In ne reprt, PD had little effect n chest pain, which is present in 40 t 60 percent f patients.

29 Achalasia Cmplicatins f PD Perfratin (2-6%) Bleeding Intramural hematma Diverticula at the gastric cardia Severe pstprcedural chest pain (15%) GERD (2%) Mrtality (0.2%)

30 Pneumatic Dilatin Cmplicatins (perfratin) Usually present in the first dilatin sessin, in the distal left side f the esphagus. Findings: tachycardia and chest pain that lasts fr mre than fur hurs. May be managed with cnservative treatment such as antibitics and parenteral nutritin.

31 Pneumatic Dilatin Cmplicatins (perfratin) Clinical deteriratin r the presence f freeflwing barium int the mediastinum requires immediate thractmy and repair. Mrtality rate can be very high (5-75%) and crrelates with delays in bth diagnsis and treatment.

32 Pneumatic Dilatin Cmplicatins (perfratin) The endscpic clsure by clips is indicated when the diagnsis is made during the PD. Hwever, bservatin f wrsening signs and a tight cperatin with the thracic surgens is recmmended.

33 Pneumatic dilatin predictrs f utcme Pst-dilatin LES pressure (<10 mm Hg) Older age (>40 years) Female sex Yung males may benefit frm an initial PD with a 3.5 cm balln.

34 Achalasia Pneumatic dilatin Other frms f therapy shuld be cnsidered fr patients wh have had tw r three unsuccessful PDs. PD shuld be attempted befre mytmy during pregnancy.

35 ACHALASIA BT befre PD wuld benefit a grup f achalasia patients. Efficacy f BT befre PD We can use cmbined treatment in the patients d nt respnd well t tw sessins f PD (especially in lder patients>40 years ld). Interval between BT & PD : ne mnth( in ur study), 7 days (Hep A study), simultaneus ( Chinese study )

36 ACHALASIA Efficacy f BT befre PD In a RCT 90 patients were assigned t BT, PD, r bth BT injectin and PD. The respnse rate at tw years was significantly higher with cmbinatin therapy (57% versus 14% with BT and 36% with PD).

37 Achalasia- Mytmy Open surgical mytmy Laparscpic Heller mytmy Rbtic Heller mytmy Perral endscpic mytmy

38 Achalasia-Mytmy Respnse Rate: At 1 year 85-90% At 10 years 70-85% At 20 years 65-73% Mrtality Rate: 0.03% Mrtality rate is similar t PD

39 Surgical Mytmy The additin f a fundplicatin reduce the rate f pstmytmy GERD (4 versus 32 percent).

40 Laparscpic mytmy A single-center series f 407 patients The five-year respnse rate was 87 percent. Mst failures ccurred within 12 mnths, and the majrity f patients were treated with PD. The presence f chest pain r a sigmidshaped esphagus predicted failure.

41 Mytmy versus PD A randmized trial (201 patients), fund similar efficacy fr PD and mytmy after tw years. (86 and 90%, respectively) In sme studies mytmy was mre effective than PD. (85% versus 65% in lng-term fllw up. Okike et al.)

42 Achalasia- treatment ptins The decisin between PD and mytmy as initial therapy shuld be based upn the patient's preferences and n the availability f experienced persnnel.

43 ACHALASIA PD versus Mytmy If there is expertise in bth prcedures, we suggest pneumatic dilatin. A dilatin- first, mytmy fr nnrespnders may be the better therapeutic apprach.

44 ACHALASIA (Treatment) Decisin analysis and cst-effectiveness Surgical mytmy was the mst cstly strategy. Althugh the initial cst was lwer fr Btx than fr surgery, the verall csts were similar by tw years. PD was the mst cst-effective treatment strategy ver a five-year time hrizn.

45 Late recurrence f dysphagia after mytmy r PD Return f tne in the damaged LES muscle GERD with peptic stricture frmatin squamus cell carcinma f the esphagus Endscpic examinatin shuld readily differentiate these disrders.

46 Endscpic injectin f ethanlamine as a treatment fr achalasia Mret treated 33 patients by repeated injectin f ethanlamine leate at LES. Mean fllw-up: 31.5 mnths Mean f treatment sessins: 3.6 The result was excellent r gd in 31 f the 33 patients after 1 mnth.

47 Endscpic injectin f ethanlamine as a treatment fr achalasia (cnt.) This imprvement was sustained fr mre than 2 years. Nne f the patients wh were fllwedup had t underg surgery due t failure f the treatment.

48 Endscpic injectin f ethanlamine as a treatment fr achalasia (cnt.) Cmplicatins: Mild reflux esphagitis (5 cases) Transient thracic pain (6 cases) Mild fever r chills (5%) Fibrtic stricture (4 cases)

49 Ethanlamine Oleate in Achalasia Ethanlamine leate in resistant idipathic achalasia: a nvel therapy Ramin Niknam, Javad Mikaeli, Narges Mehrabi, et al. Eurpean Jurnal f Gastrenterlgy & Hepatlgy 2011.

50 Ethanlamine Oleate in Achalasia Methds: We evaluated the efficacy f EO in patients that are resistant t r pr candidate f PD and/r cardimytmy. Diluted EO (2.5%) was injected at LES. Injectin was repeated at 2 and 4 weeks after first injectin.

51 Ethanlamine Oleate in Achalasia Results: All patients had gd respnse. (symptm scre decreased> 50% and height and vlume f barium in TBE decreased > 50%) The mean symptm scre decreased frm t 3.23 at 1.5 mnths after the last injectin (P = 0.001).

52 Ethanlamine Oleate in Achalasia The mean duratin f fllw-up was (± 1.12) mnths. Relapse was bserved in six patients; all were re-injected nce that prved t be effective.

53 ACHALASIA (Future therapies) If the hypthesis f an autimmune cause were cnfirmed, tpical r systemic immunsuppressive therapy might be wrth a trial. Implanting new inhibitry neurns may prvide a cure fr achalasia.

54 Stem cell transplantatin in neurdegenerative disrders f the gastrintestinal tract The principal activities f the gut, including mtility and secretin, are largely cntrlled by the intramural enteric nervus system (ENS). The ENS is cmpsed f millin neurns and many mre glial cells.

55 Stem cell transplantatin Enteric neural stem cells (ENSC) are widely distributed in the gut. ENSC may be readily accessible by endscpic (mucsal bipsy) r minimally invasive surgical techniques.

56 Stem cell transplantatin If stem cells are s ubiquitus in the gut, why des neurnal lss ccur at all in sme diseases? This culd be due t a defect in the stem cells r a disturbance in the hst envirnment that prevents them frm generating new neurns.

57 Stem cell transplantatin Lcal injectin by endscpic r surgical means, is the mst direct rute fr lcalised diseases. ENSC can als be delivered intraperitneally r intravascularly and may be able t hme in t the gut by as yet unidentified cues.

58 Stem cell transplantatin NSC transplantatin represents an ideal way t treat achalasia in which there is a clearly defined neurnal lss. Because ENSCs in ther regins f the gut such as the cln are nt affected, there is a real ptential fr autlgus transplantatin that alleviate the need fr immunsuppressin.

59 Perral endscpic mytmy The key prcedures f POEM: Midesphageal mucsal incisin Submucsal "tunneling" by endscpic submucsal dissectin Mytmy f the circular muscle at the lwer esphageal sphincter Clsure f mucsal incisin by hemstatic clips

60 Perral endscpic mytmy POEM was ffered as an alternative t laparscpic r rbtic Heller mytmy

61 Perral endscpic mytmy Exclusin criteria: Pregnancy Prir esphageal surgery Immunsuppressin Cagulpathies Severe medical c-mrbidities

62 Perral endscpic mytmy Operative time ranged frm 60 t 240 minutes. (under general anesthesia) Mean submucsal tunneling length is 12 cm. The average length f endscpic mytmy is 7 cm.

63 Perral endscpic mytmy CONCLUSIONS: As a nvel minimally invasive therapy, POEM appears t have definite shrtterm utcmes. POEM significantly reduce dysphagia and resting LES pressure.

64 Perral endscpic mytmy Lng fllw-up is needed t evaluate lngterm utcme and n cmparisn f POEM with ther therapies. Cmplicatins: submucsal fistula, GERD pneumperitneum, Subcutaneus emphysema - N serius cmplicatins

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