Steven Frachtman, M.D. Division of Gastroenterology/Hepatology August 18, 2011

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1 Steven Frachtman, M.D. Division of Gastroenterology/Hepatology August 18, 2011

2 Review normal esophageal anatomy and physiology Classifications of esophageal motility disorders Clinical features/diagnosis/management of specific disorders

3 20-22 cm muscular tube (skeletal + smooth) Proximal 5% striated including the UES, middle 35-40% smooth, distal 50-60% entirely smooth Peristalsis controlled by: 1. Extrinsic innervation via the vagus nerve 2. Autonomous control in the myenteric plexus

4 Proximal striated muscle receives excitatory vagal innervation only Distal smooth muscle/les receives vagal innervation via synapses within the myenteric plexus (autonomic nerve network between the longitudinal and circular muscle layers) Excitatory neurons mediate contraction via nicotnic cholinergic receptors Inhibitory neurons mediate relaxation via nitric oxide inhibition of muscarinic cholinergic neurons

5 Primary peristalsis initiated by a swallow, secondary peristalsis by esophageal distention Deglutitive inhibition: second swallow (initiated while an earlier peristaltic contraction is still progressing) causes inhibition of the contraction induced by first swallow 1. Vagal mediated contraction in the proximal esophagus 2. Vagal mediated contraction/inhibition in the distal esophagus via the myenteric plexus 3. Autonomous myenteric plexus control of peristaltic progression/secondary peristalsis

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8 Dysphagia to both solids and liquids Associated GERD, regurgitation, chest pain, odynophagia Absence of immediate symptoms, associated aspiration, or cough (suggestive of oropharyngeal dysphagia) Patient localization of obstruction in esophageal dysphagia is inaccurate

9 Barium swallow with tablet EGD MBS (1. delay in initiation of pharyngeal swallowing 2. aspiration 3. nasopharyngeal regurgitation 4. residue of the ingestate within the pharyngeal cavity after swallowing) Esophageal manometry: most useful when esophageal motility disorder suspected (obstruction or oropharyngeal cause ruled out), in confirming a diagnosis of Achalasia, pre-op assessment prior to anti-reflux surgery

10 Primary vs. Secondary disorders (associated with generalized disease) Chicago Classification (Normal vs. Impaired GEJ relaxation Hypercontracting vs. Hypocontracting esophagus

11 Hypercontracting Esophagus: DES Nutcracker Hypertensive LES Hypocontracting Esophagus: Primary Achalasia Secondary Achalasia/Impaired Esohageal Motility: Connective tissue diseases, Endocrine diseases, Neuromuscular diseases, Paraneoplastic syndromes

12 Epidemiology Most easily recognized and best defined motor disorder of the esophagus Annual incidence 1/100,000 Affects both genders equally Presents between ages yrs old Reports of familial clustering but a genetic determinant is not strong

13 Pathogenesis Characterized by impaired LES relaxation with swallowing and aperistalsis in the smooth muscle esophagus Resting LES pressure elevated in about 60% of cases (normal mmhg) Loss of inhibitory neurons in the Myenteric Plexus which mediate deglutitive inhibition (including LES relaxation) and sequenced propagation of esophageal peristalsis Autoimmune response to viral infection (HSV-1 possible culprit)

14 Clinical features: Solid food dysphagia with variable degrees of liquid dysphagia Nocturnal regurgitation Chest pain (spasm, progressive esophageal dilation) Paradoxical complaint of heartburn (periods of esophageal acidification due to bacterial fermentation of retained food as opposed to frank GERD) Weight loss Aspiration/Choking

15 Risk of Squamous Cell Cancer Relative risk estimated at 33-fold Exact pathogenesis unclear but stasis esophagitis a likely precipitating factor Often advanced at time of detection Given 0.15% incidence, surveillance program currently not the standard practice

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19 Chagas disease Endemic to Brazil, Venezuela, Argentina Spread by bite of reduvid bug that transmits T. cruzi Destruction of autonomic ganglion cells (can be indistinguishable from Achalasia) Most obvious clinical distinction is evidence of additional organ involvement Treatment for esophageal involvement similar to Achalasia

20 Pseudoachalasia: Tumor related pseudoachalasia accounts for up to 5% of cases with manometrically defined achalasia More likely in older age groups, recent onset of symptoms, early weight loss Tumor infiltration (carcinoma in gastric fundus) can completely mimic functional impairment in achalasia (thorough examination during EGD) Higher resistance to scope passage across GE junction

21 Pseudoachalasia: Adenocarcinoma of GE junction accounts for more than ½ of pseudoachalasia cases Pancreatic, hepatoma, lung, SCC esophagus, prostate, lymphoma reported (infiltrating wall of esophagus at GE junction) Esophageal infiltration by Amyloid Paraneoplastic syndrome?

22 Postsurgical: Aperistalsis and impaired LES relaxation can be seen following fundoplication Administer amyl nitrite during manometry Mechanical effect of a fundoplication is less affected by the smooth muscle relaxing effects compared to the hypertensive sphincter of a person with achalasia

23 Pharmacologic Therapy Largest reported experience with Isordil and Nifedepine Isordil 5 to 10 mg sl qac reducing LES pressure by 66% for about 90 mins (no placebo controlled trials) Nifedepine 10 mg sl qac reduced LES pressure by 30-40% for more than one hour (subsequent placebo controlled trials showed minimal benefit)

24 Botox injections Initial landmark study reported injection of 80 units (divided doses into 4 quadrants of the LES) decreased LES pressure by 33% and improved dysphagia in 66% of patients for 6 month period Irreversibly inhibits release of acetylcholine from presynaptic cholingergic terminals Inhibitory effect eventually reversed by growth of new axons Not a long lasting therapy; minimal continued efficacy at one year Reserved for older patients who are not candidates for more definitive therapy

25 Pneumatic Dilation Therapeutic dilation requires distention of LES to diameter of at least 3 cm for lasting reduction of LES pressure (partially disrupting circular muscle of the sphincter) Dilation with endoscope, standard bougies, balloon dilators provides temporary benefit at best Achalasia dilator: long noncompliant cylindrical balloon that can be positioned across LES fluoroscopically or endoscopically and inflated in a controlled fashion with a handheld manometer

26 Pneumatic Dilation Technique variable in terms of patient preparation, parameters of balloon inflation, and post-dilation monitoring Cautious approach of starting with small diameter dilator (3 cm) and progressing only when smaller dilator ineffective is fairly universal Proper position at LES (observe waist of the hourglass shaped balloon silhouette and that the waist fully effaces as inflation proceeds)

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28 Pneumatic Dilation Major complication is esophageal perforation (1% to 5%) Fluoroscopic examination after dilation (water soluble contrast followed by barium) Suspect when there is post-procedure pain or subcutaneous emphysema If perforation appears small, contained, intramural then conservative management in hospital Substantial perforation surgical repair Best predictor of efficacy is post-dilation LES pressure less than 10 mmhg

29 Pneumatic Dilation In cases of unsatisfactory result, reasonable to perform subsequent dilation within matter of weeks If benefit lasted > 1 yr, neither unusual or dangerous to repeat dilation as necessary Clinical efficacy 32% to 98% Patient with poor initial result or rapid recurrence of symptoms are less likely to respond to additional dilations Subsequent response to surgical myotomy not influenced by history of previous dilations

30 Heller Myotomy Offers more predictable method of reducing LES pressure Considerable morbidity related to thoracotomy Laparoscopic approach with similar efficacy, reduced morbidity Overall mortality less than 2% Published series report good to excellent results in 62 to 100% of pts with persistent dysphagia present in less than 10% Postmyotomy reflux Laparoscopic Heller myotomy combined with partial fundoplication become preferred surgical procedure Unsatisfactory results: incomplete myotomy, scarring of myotomy, functional esophageal obstruction

31 DES Nutcracker Esophagus Hypertensive LES

32 Epidemiology Also known as distal esophageal spasm (only smooth muscle affected) A disorder or peristalsis but in most pts, esophagus retains ability propagate normally majority of the time No known risk factors or other associated conditions Neuromuscular pathology more subtle than in Achalasia and is unknown Most striking reported pathologic change is diffuse muscular hypertrophy/hyperplasia in distal esophagus Despite absence of defined histopathology, physiologic evidence suggests myenteric plexus neuronal dysfunction

33 Epidemiology: Vagal impulses reach entire smooth muscle segment of esophagus simultaneously and activate myenteric plexus neurons Ganglionic neurons intervening between vagal fibers and smooth muscle belong to either inhibitory population (inhibit contraction) or excitatory population (promoting contraction) Experimental evidence suggest heterogeneity among patients, some with primarily a defect in inhibitory function vs. others with primarily excess excitation Imbalance between excitatory and inhibitory influences on the esophageal smooth muscle

34 Clinical Features: Main symptoms are dysphagia and chest pain Dysphagia usually intermittent and sometimes related to swallowing specific substances (liquids at extreme temps) Chest pain description often sounds like angina Pain lasts mins to hours; continued swallowing not always impaired Mechanism of pain unclear sustained contraction? Symptoms non-specific Rule out more common esophageal disorders (peptic or infectious esophagitis)

35 Diagnosis Barium Swallow: Radiographic findings variable from normal to severe non-peristaltic contractions that can produce striking abnormalities in barium column ( corkscrew esophagus )

36 Diagnosis Manometry: Variety of motility patterns high amplitude (>180 mmhg), repetitive simultaneous, and prolonged duration contractions (>6sec) 20% or more simultaneous contractions in distal esophagus is hallmark to suggest the diagnosis 1/3 of pts with DES will have associated abnormalities of the LES including high resting pressure (> 40 mmhg) or incomplete relaxation

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39 Manometric finding of high amplitude peristaltic contractions in the distal 10 cm of the esophagus with average pressures exceeding 220 mmhg Normal deglutitive LES relaxation The following may or may not be present: repetitive contractions (> 2 peaks), prolonged contractions (>6sec), increased resting LES pressure (>40 mmhg) Studies using high frequency intraluminal US have demonstrated asynchronous contractions of the circular and longitudinal muscle layers Asynchrony reversed after administration of atropine (suggesting pathogenesis in part related to hypercholinergic state)

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41 Manometric finding of increased resting LES pressure (> 40 mmhg) Incomplete relaxation may be present Two studies demonstrated that 50% of patients with hypertensive LES also had the high amplitude distal peristaltic waves of nutcracker esophagus

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43 Specific therapies difficult to define since both the pathophysiology and relation of motility findings to symptoms remain obscure Minimal data from prospective controlled observations; those that are positive with small number patients Therapies initially centered on improving esophageal contractility and emptying (limited efficacy other than in achalasia)

44 Treatment with smooth muscle relaxants supported by clinical trials but response is variable at best Positive anecdotal results with nitrates, anticholinergic drugs, bougie dilation, botox, sidenafil 29 symptomatic pts with spastic motility disorder treated with total of 100 units z-line. Response(50% reduction in sx s) seen in 70% of patients with average duration of relief 7 months. (Miller et al, Am J Gastro 2002) Sildenafil (50 mg po qd) associated with symptom relief in group of 11 pts with spastic motility disorders (Eherer et al Gut 2002) Minimal clinical support/greater potential adverse effects Pneumatic dilation Esophagomyotomy

45 Paradigm shift: abnormal manometric findings indicative of symptomatic hypercontractility states may actually be related to hypersensitivity syndromes or external stimuli (GERD) Many pts with hypercontracting esophagus have GERD and have improvement in symptoms with PPI (Achem et al Am J Gastroenterology 1993). Trazadone shown to be effective in controlled trials in relieving chest pain (Clouse et al, Gastro 1987)