The Lower Esophageal Sphincter in Health and Disease. Steven R. DeMeester Professor and Clinical Scholar Department of Surgery

Transcription

1 The Lower Esophageal Sphincter in Health and Disease Steven R. DeMeester Professor and Clinical Scholar Department of Surgery

2 The Lower Esophageal Sphincter Dual function: allow bolus from esophagus into the stomach and prevent reflux of gastric contents back into the esophagus

3 The History Manchard P. Br J Surg, 1955

4 Esophago-Gastric Junction They were all right! Manchard P. Br J Surg, 1955

5 Components of the Antireflux Barrier Intrinsic sphincter (LES) Crural diaphragm Phrenoesophageal ligament Angle of His

6 The LES: Obvious, Simple yet Incredibly Complex A band of pressure formed by the longitudinal and circular muscles of the distal esophagus in combination with the clasp and sling fibers of the proximal stomach Liebermann-Meffert D, et al. Gastro, 1978

7 Anatomy of the LES Region Liebermann-Meffert D, et al. Gastro, 1978

8 LES Function and Physiology The LES is innervated by vagal preganglionic and sympathetic postganglionic efferents LES tonic contraction is primarily myogenic (absence of exogenous control) LES myoctyes are more depolarized than those in the esophageal body The resting and active neuromuscular properties of the LES are complex (and still incompletely understood) but depend on the interplay of myogenic and neural mechanisms (excitatory cholinergic and inhibitory nitrergic) Kwiatek MA, Kahrilas PJ. Dis Esoph, 2012

9 The LES No distinct anatomic boundaries Debate about whether the muscle is thicker in the LES region (under normal circumstances) HF-EUS studies in normal volunteers Pehlivanov N, et al. Am J Physiol Gastrointest Liver Physiol, 2001

10 The Resting LES as Seen on Manometry Three critical parameters for function Overall length, abdominal length and pressure Lower limits of normal: OL 2 cm, AL 1 cm, Pressure 6 mmhg n=41 normals Zaninotto G, et al. Am J Surg, 1988

11 LES by Slow Motorized Pull-Through Campos GMR, et al. Dig Disease Sci, 2003

12 High Resolution Manometry 36 sensors spaced 1 cm apart with each sensor containing 12 radially dispersed sensing elements over 2.5 mm

13 LES Length on HRM Niebisch S, Wilshire CL, Peters JH. Dis Esoph, 2013

14 HRM Normal LES Values 68 normal subjects Median age 25.5 years (20-58) 53% female Niebisch S, Wilshire CL, Peters JH. Dis Esoph, 2013

15 HRM Normal Values Herregods TVK, et al. Neurogastroenterol Motil, 2015

16 3-D Imaging of the LES Stein HJ, et al. Ann Surg, 1991

17 3-D Imaging of the LES Patient with Barrett s Normal Volunteer Stein HJ, et al. Ann Surg, 1991

18 Correlation of SPVV with Anatomy Greatest muscle thickness and pressure posterior lateral along GC Stein HJ, Lieberman-Meffert D, DeMeester TR, Siewert JR. Surgery, 1995

19 Standard Manometry Vs SPVV Stein HJ, et al. Ann Surg, 1991

20 High Definition 3D Manometry

21 3-D HRM Catheter Kwiatek MA, et al. Neurogastroenterol Motil, 2011

22 Asymmetry with 3-D HDM 15 normals (CD / GC) (lesser curve) Kwiatek MA, et al. Neurogastroenterol Motil, 2011

23 HRM vs 3-D HDM LES length was significantly less when measured with 3-D HDM at both peak inspiration (2.3 vs 5.0 cm, p<0.05) and expiration (2.4 vs 5.0 cm, p<0.05) HRM is overes+ma+ng sphincter length! Kwiatek MA, et al. Neurogastroenterol Motil, 2011

24 LES Relaxation

25 Deglutitive LES Relaxation In response to a swallow LES relaxes after which there is a rebound contraction Relaxation typically occurs within 2 seconds of the pharyngeal swallow and persists for up to 10 seconds Deglutitive LES relaxation mediated via vagal inhibitory pathway and release of nitric oxide During LES relaxation diaphragmatic electrical activity is inhibited Bilateral vagotomy does not significantly alter basal LES pressure but inhibits swallow-associated LES relaxation and abolishes the inhibition of crural activity Kwiatek MA and Kahrilas PJ. Dis Esoph, 2012

26 Integrated Relaxation Pressure Kahrilas PJ, et al. Neurogastroenterol Motil, 2012

27 Axial Stretch and LES Relaxation Swallowing associated with axial movement of the LES upwards ~ 20 mm as a consequence of contraction of the longitudinal esophageal muscle Animal models demonstrate that axial stretch as well as balloon distension in the esophagus induces LES relaxation Abolished by NO inhibitor Not impacted by bilateral vagotomy or symphathectomy Blocked by tetrodotoxin (neurotoxin) Findings suggest process is mediated through direct activation of motor neurons in the myenteric plexus of the LES Jiang Y, Bhargava V, Mittal RK. Am J Physiol Gastrointest Liver Physiol, 2009

28 Axial Stretch Model Dogan I, et al. Am J Physiol Gastrointest Liver Physiol, 2006

29 Transient LES Relaxation(s) Abrupt decrease in LES pressure to the level of intragastric pressure not triggered by swallowing Typically longer duration (10-45 seconds) then a swallowinduced LES relaxation Associated with distal esophageal pressure waves, small decrease in intra-gastric pressure and inhibition of the crural diaphragm Can be associated with reflux In normal subjects linked with the majority of reflux episodes In patients with GERD mechanism of reflux less homogeneous, proportion related to TLESRs varies inversely with the severity of reflux disease Mittal RK, et al. Gastro, 1995

30 Transient LES Relaxation Triggered by gastric distension, but suppressed in supine position, during sleep and general anesthesia Believed to be a vagal reflux stimulated by receptors in the gastric fundus and pharynx Absence in patients with achalasia suggests that TLESRs share common final pathway with swallow-induced LES relaxation TLESRs are reduced by: NO inhibitor Fundoplication Mittal RK, et al. Gastro, 1995

31 TLESR on Manometry Mittal RK, et al. Gastro, 1995

32 TLESRs and Esophageal Shortening Pandolfino JE, et al. Gastro, 2006

33 TLESR or Transient LES Shortening? 9 healthy volunteers drank 355 ml can of tap water then subsequently sparkling water or cola with manometry catheter in place Done in supine position, belching uncommon No significant changes in LES after tap water After carbonated beverage in 62% of subjects with normal baseline parameters the LES became defective (abd length) Hamoui N et al. J Gastrointest Surg, 2006

34 High-Resolution Impedance Manometry

35 Bolus Pressure Kahrilas PJ, et al. Neurogastroenterol Motil, 2012

36 Bolus Pressure (3 seconds) (4 seconds) Scherer JR, et al. J Gastrointest Surg, 2009

37 EGJ Distensibility Increased GEJ distensibility could have major implica+ons on the volume of reflux Volume of flow through EGJ propor+onal to opening diameter raised to 4 th power Kwiatek MA, et al. Gastrointest Endosc, 2010

38 LES and the Crura Normally superimposed and the crura contribute to the barrier function of the esophagogastric junction (particularly during inspiration) A hiatal hernia leads to spatial separation of LES and crura and impairment of EGJ barrier function Relationship of LES and crura best understood with manometry

39 LES and Crural Separation Banki F, et al. Am Surg, 2001

40 Normal HRM : Overlap of LES and Crura Type I Pandolfino JE, et al. Am J Gastro, 2007

41 Early Separation Type II Pandolfino JE, et al. Am J Gastro, 2007

42 Hiatal Hernia (> 2 cm Separation) Type IIIa Type IIIb (Tight crura) (Wide hiatus) Pandolfino JE, et al. Am J Gastro, 2007

43 Impact of Crural / LES Separation Pandolfino JE, et al. Am J Gastro, 2007

44 Role of the Angle of His Manchard P. Br J Surg, 1955

45 Esophago-Gastric Dysfunction Inadequate resistance: GERD

46 GERD 60% of patients with a positive ph test had a mechanically incompetent sphincter based on pressure ( 6mmHg), overall length (<2 cm) or abdominal length (<1 cm) Isolated low LES pressure was the most common abnormality followed by low LES pressure combined with short abdominal length n=622 Zaninotto G, et al. Am J Surg, 1988

47 LES Parameters and GERD ZaninottoG, et al. Am J Surg, 1988

48 Vector Volume and GERD Stein HJ, et al. Ann Surg, 1991

49 LES and GERD Severity Prevalence of a defective LES Ayazi S, et al. Surg Endosc, 2011

50 LES, HH and GERD Fein M, et al. J Gastrointest Surg, 1999

51 LES, HH and GERD Fein M, et al. J Gastrointest Surg, 1999

52 LES, HH and GERD Fein M, et al. J Gastrointest Surg, 1999

53 LES, HH and GERD Severity Variable GERD no BE SSBE LSBE Prevalence of hh 56% 73% 94% Size of hh (cm) LES total length (cm) LES abdominal length LES pressure (mmhg) Defective LES 69% 81% 99% Campos GMR, et al. Arch Surg, 2001

54 Restoring LES Parameters Fundoplication n=10 adult baboons Mason RJ, et al. Arch Surg, 1997

55 Fundoplication for GERD Reduces the effect of gastric distension on sphincter length n=10 adult baboons Mason RJ, et al. Arch Surg, 1997

56 Fundoplication for GERD Reduces vagal nerve stimulated and axial stretch induced LES cranial displacement and relaxation Rat model Jiang Y, et al. Gastro, 2011

57 Fundoplication for GERD Reduces TLESRs Bahmeriz F, et al. Surg Endosc, 2003 Scheffer RCH, et al. Am J Physiol Gastrointest Liver Physiol, 2003

58 Fundoplication and Compliance / Distensibility Kwiatek MA, et al. J Gastrointest Surg, 2010

59 LES Augmentation LINX Sphincter Augmentation Device

60 LES Augmentation Low Frequency LES Stimulation n= 4 animals Sanmiguel CP, et al. Am J Physiol Gastrointest Liver Physiol, 2008

61 Esophago-Gastric Dysfunction Failure of relaxation

62 Achalasia

63 HRM Achalasia Types Type I Type II Type III Incomplete relaxation (elevated IRP)

64 HRM with Impedance

65 Muscle Hypertrophy Mittal RK, et al. Am J Gastro, 2003

66 Muscle Thickness and Contraction Amplitude Pehlivanov N, et al. Am J Physiol Gastrointest Liver Physiol, 2001

67 Reduced IRP with Myotomy TBS, 5 minutes Pre: 48% Post: 100% Swanstrom LL, et al. Ann Surg, 2012

68 LES In Achalasia Outcome of therapy related to muscle thickness? Related to loca+on of myotomy? Korn O, et al. Dis Esoph, 2000

69 EJG Distensibility in Achalasia Pandolfino JE, et al. Neurogastroenterol Motil, 2013

70 Functional EGJ Obstruction with Intact Peristalsis Scherer JR, et al. J Gastrointest Surg, 2009

71 Difficult Group Is it secondary to another process? Hiatal hernia, eosinophilic esophagitis, reflux Do symptoms improve with botox or other measures aimed at reducing dysfunction? Results with non-myotomy therapy have been disappointing Scherer JR, et al. J Gastrointest Surg, 2009

72 Conclusions The normal LES is complex and similar to the 5 blind men and the elephant, we understand it differently depending on how we look at it EGJ antireflux barrier consists of crural diaphragm, intrinsic LES, phrenoesophagal ligament and the angle of His Likely a benefit to evaluating patients with each of these components in mind Tailor therapy based on presence and severity of the abnormalities in EGJ barrier function