Esophageal Disorders

Educational Objectives

The goal of this program is to improve the management of esophageal disorders. After hearing and assimilating this pro­gram, the clinician will be better able to:

1.   Recognize eosinophilic esophagitis (EE), based on symptom presentation and x-ray findings.

2.   Describe the pathophysiology of EE.

3.   Distinguish among types of dysphagia.

4.   Utilize various techniques to evaluate dysphagia.

5.   Discuss methods for treatment of esophageal varices.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Madanick is on the Speakers’ Bureau of AstraZeneca. Drs. Richter and Awad and the planning committee reported nothing to disclose. In their lectures, Drs. Richter and Madanick presented information related to off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Richter was recorded at the 33rd Annual Texas Program, held September 19-21, 2008, in Austin, TX, and sponsored by the Texas Society for Gastroenterology and Endoscopy, the American College of Gastroenterology, and the Society of Gastroenterol­ogy Nurses and Associates Texas Regional Societies. Dr. Madanick was recorded at Update in Gastroenterology and Hepatology: Applying Sound Principles in Daily Practice, held April 17-19, 2009, in Chapel Hill, NC, and sponsored by the University of North Carolina School of Medicine. Dr. Awad was recorded at Gastroenterology and Hepatology Update 2008, held September 19, 2008, in Nashville, TN, and sponsored by the Vanderbilt University School of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition and Division of Continuing Medical Education. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Eosinophilic Esophagitis (EE)

Joel E. Richter, MD, Professor and Chair, Department of Medicine, Temple University School of Medicine, Philadel­phia, PA

Presentation: majority of patients men, age range 36 to 42 yr, and predominantly white; generally seen in Westernized countries and in multiple family members; nearly all have solid-food dysphagia; »50% with history of food impaction; approximately one-third present with heartburn; many diagnosed with gastroesophageal reflux disease (GERD); small subset present with chest pain and vomiting; ongoing allergic diseases in many patients; pattern of exacerbations related to pollen season; most common presentation ringed esophagus; furrows up and down esophagus common; in children, pustules represent small eosinophilic abscesses (rare in adults); x-ray findings  —  “congenital” esophageal stenosis; in some patients, appearance of esophagus normal, despite complaints of solid food dysphagia; however, on barium swal­low, esophagus generally narrowed; all patients require biopsy, which shows multiple eosinophils, sometimes in aggre­gates; laboratory criteria >15 to 20 eosinophils per high power field (hpf); number of biopsies  —  study showed that using traditional criteria of ³15 eosinophils/hpf, 100% yield seen with 5 biopsies (3 from distal esophagus, 2 from prox­imal esophagus); 5% to 15% of patients have disease in proximal esophagus only; eosinophils seen in achalasia, Bar­rett’s esophagus, and esophageal cancer; presence of eosinophils does not necessarily determine diagnosis

Pathophysiology: aeroallergens or food-ingested allergens precipitate release of mast cells and T cells into blood; T cells release interleukin (IL)-5 which causes eosinophils to migrate from bone marrow to blood; eotaxins cause migration into mucosa; eotaxin-3 involved in EE; in pediatric population, group with well-defined genetic predisposition had abnormal­ity of single nuclei polymorphism in eotaxin-3 gene (not described in adults at present); improvement of eosinophilia with acid suppression seen in some children; study suggested aggressive treatment for acid reflux disease for all patients with suspected EE; epithelial recruitment  —  not specific for allergies; occurs in any condition where inflammation and damage seen in squamous epithelium; suggested that 2 diseases overlapping and contributory; GERD can lead to esoph­ageal injury and eosinophilia; possible that GERD and EE coexist but unrelated; EE can cause or contribute to GERD; re­lease of cytokines causes dysmotility; GERD can cause or contribute to EE; dilation of intercellular spaces earliest finding on electron microscopy of patients with heartburn; allows acid and allergens to enter; aggressive treatment with proton pump inhibitors (PPIs) allows dilated spaces to return to normal

Treatment: in pediatric population, elimination diet effective, particularly enteral feedings; role for allergy testing and selective elimination; drug therapies  —  in pediatric population, resolution of eosinophilia seen with systemic and inhaled steroids (better results with oral prednisone); however, recurrence of eosinophilia seen as soon as steroids stopped; study  —  oral pred­nisone and fluticasone found equally effective in improving symptoms and resolving EE; adverse effect rate higher with prednisone; after 24 wk, 50% had relapsed; inhaled steroids  —  in adults, allergic component treated aggressively with fluti­casone or inhaled steroids given bid (after breakfast and dinner); duration variable (average 6 wk); spacer removed to ensure delivery to esophagus (rather than lungs); patient should inspire deeply, depress inhaler, and swallow aerosol, then rinse mouth with water; avoid food and water for 2 to 3 hr; important that inhaled steroids have contact with esophageal mucosa; study  —  participants with EE, ringed esophagus, and dysphagia treated with fluticasone for 6 wk; results after 4 mo showed complete symptom relief in 92%; all participants back on steroids within 3 yr, and >50% required further dilations; study  —  showed that even on placebo, some patients achieved resolution of eosinophilia; nonallergic patients had better outcome with fluticasone than allergic patients; montelukast (Singulair)  —  leukotriene receptor antagonist which blocks leukotriene D4 receptors, reducing inflammatory action of eosinophils; no resolution of eosinophilia; study found 6 of 8 patients with EE treated with montelukast had complete resolution; anti-interleukin (IL)-5 agents  —  given in 3 infusions in pediatric popu­lation; effective; esophageal dilation  —  study of patients with ringed esophagus and history of food impaction treated with gradual dilations and PPI; at 2 yr, all but one patient achieved good response

Esophageal tears and rents: concern in dilations; painful; frequency variable; hardly ever requires surgery; occurs in muscle layer; sometimes associated with pneumomediastinum, requiring hospital stay of 7 to 10 days for medical therapy; risk factors  —  long duration of dysphagia; narrow esophageal rings; high density of eosinophils; start slowly, progress slowly, and usually dilate to only 15 to 16 mm

Dysphagia: New Thoughts on Old Problem

Ryan D. Madanick, MD, Assistant Professor of Medicine, University of North Carolina, School of Medicine, Chapel Hill

Definition: often, patient who reports inability to swallow really experiencing oropharyngeal dysphagia; sensation of food being hindered in its passage from mouth to stomach; transfer dysphagia  —  difficulty getting food in mouth, from mouth to pharynx, and from pharynx to esophagus; transport dysfunction  —  inability to move food down esoph­agus or lodging of food in distal esophagus; nonobstructive dysphagia  —  obstruction absent, but sensation of inabil­ity to swallow or difficulty with food going down present; residual diagnosis once other problems ruled out; abnormal sensory perception  —  sensation of something in esophagus perceived as swallowing problem; overlaps with nonob­structive dysphagia, but actually hypersensitivity issue

Assessment: location  —  when location of problem pointed out, possible source anywhere from that point down; course  —  progressing or worsening over time (ominous sign); frequency  —  with every swallow (likely fixed defect or severe esophageal motility issue) or intermittent (likely spastic or very slight ring); kind of food  —  solid, liquid, or both; if solids only, likely structural or anatomic problem; if liquids only or both, severe anatomic problem or motility disorder; association with respiratory symptoms  —  “choking”; oropharyngeal or esophageal regurgitation into throat; association with pain  —  presence of odynophagia indicates esophagitis; spastic or squeezing pain more likely spastic problem; warning signs  —  weight loss; heartburn; work-up  —  first step determining whether dyspha­gia oropharyngeal or esophageal; if difficulty initiating swallow, consider oropharyngeal problem; if food goes down but, gets caught, consider esophageal problem; ask whether problem with solids, liquids, or both, whether in­termittent or progressive, and whether heartburn present

Oropharyngeal dysphagia:  once diagnosis made, look for correctable problems; if not correctable, everything else quality of life issue; determine functional integrity of swallow with flexible endoscopic evaluation of swallowing (FEES; done by otolaryngologist) or modified barium swallow; minor role for manometry; main issue risk for aspi­ration and whether any problem identified amenable to therapy; few problems amenable to therapy, unless stricture or systemic disorder (eg, polymyositis, dermatomyositis); speech and swallowing therapy for stroke patients

Globus sensation: determine whether it occurs after eating; if patient eats, and later notes sensation of food being stuck, globus; if patient eats and immediately gets sensation of food being stuck, but relieved »1 hr later, not globus; possibly associated with GERD, but probably hypersensitivity disorder; strong predilection for association with anxiety; im­proves with eating; inability to swallow seen in 10% to 15% of patients

Postfundoplication dysphagia: incidence  —  variable and unpredictable; seen in almost all patients in first few weeks after procedure; should be given postfundoplication diet, then slowly advanced over time; long-term problems not seen in most patients; after 3 to 6 mo, 5% to 10% of patients have persistent dysphagia; only small percentage require revision, and £3% require dilation; theories on etiology  —  not always due to tight wrap; possible true alteration in lower esophageal sphincter (LES) function; possible change in esophageal function; extrinsic complication of cruro­plasty

Gas bloat syndrome: inability to expel gas from stomach after fundoplication; presenting symptoms abdominal pain, bloating, and inability to belch; possibly amenable to dilation therapy, but in some cases, severe enough to require removal of wrap; etiology  —  unknown but possibly due to inappropriately small dilator or dilator not used during surgery (use of dilator during surgery not considered standard of care) other possibility scarring around esophagus from leak or electrocautery

Evaluation of dysphagia: impedance  —  opposition to flow of electric current; measures resistance to flow of ions across rings; the higher the flow, the more conductive bolus is, and the lower the impedance; good conductance and low impedance seen with saline; poor conductance and high impedance seen with air; single manometric tracing un­able to predict clearing of bolus; bolus transit differentiates patient with true bolus transit disorder vs disorder on ma­nometry; study  — shows that by adding impedance to manometry in certain group of patients (ie, those with ineffective esophageal motility or diffuse esophageal spasm), able to identify more bolus transit disorders than with manometry alone

High-resolution manometry: after fundoplication, change in pressure seen at wrap zone that translates into significant change in intrabolus pressure generated; most patients with postfundoplication dysphagia effectively managed with dilation

Management of Esophageal Varices

Joseph Awad, MD, Associate Professor of Medicine and Pharmacology, Vanderbilt University School of Medi­cine, Nashville, TN

Portal hypertension (HTN): causes  —  fibrosis of liver; blockage of hepatic venous outflow by eg, Budd-Chiari syn­drome, tumor; thrombosis of portal vein (common in cirrhosis); partly due to increased splanchnic blood flow and return upward through venous system against high resistance; patient with alcoholic hepatitis, with or without fibro­sis, can develop acute portal HTN; vascular thrombosis, especially hepatic venous outflow obstruction, possible acute cause; most of portal HTN throughout portal venous system; thrombosis of splenic vein leads to development of varices (eg, gastric; treat by ligation after removal of spleen)

Lesions of portal HTN: portal gastropathy  —  congestion of gastric mucosa; source of chronic blood loss and iron defi­ciency; gastric antral vascular ectasias  —   more difficult to treat in patients with portal HTN; “watermelon striping” towards pylorus; rectal varices  —  above usual location of hemorrhoids; portal colopathy  —  colon affected by conges­tion; usually not clinically significant; peristomal varices  —  develop after ileostomy or colostomy for ulcerative colitis; located under wafer; compress if bleeding occurs; other types  —  varices also seen in duodenum after surgery for ulcer or other surgery in gastrointestinal (GI) tract

Variceal bleeding: occurs in 25% to 30% of patients with cirrhosis; more common in advanced disease; most bleed­ing episodes in cirrhotic patients due to varices; »30% of patients die from initial bleeding; rebleeding almost al­ways occurs; bleeding diminishes survival (dependent on severity of liver disease); goals  —  identify patients at high risk for first bleeding event; reduce risk for bleeding; address reversible causes of liver disease

Before first bleeding event: guidelines recommend screening for varices in all cirrhotic patients;  esophagogastrodu­odenoscopy (EGD) traditional screening; however, if patient already on propranolol (first-line treatment for portal HTN),  EGD not necessary; if initial endoscopy negative, repeat every 2 yr until patient develops varices of suffi­cient size for institution of therapy; if small varices present, repeat endoscopy after 1 yr

Options for prophylaxis: nonselective b-blockers without nitrates primary option; data support band ligation, espe­cially in patients unable to tolerate b-blockers; sclerotherapy shown too risky; most important to educate patient that condition life-threatening and that, if signs and symptoms of GI bleeding present, should seek medical care and avoid aspirin and nonsteroidal anti-inflammatory drugs

Treatment of bleeding: admit patient to intensive care unit (ICU) and use traditional resuscitation for GI bleeding; blood and plasma used carefully; speaker rarely transfuses to hematocrit >30%; international normalized ratio (INR) does not return to normal, but keep in range compatible with  cessation of bleeding; standard of care to give IV oc­treotide initially as bolus, then as drip; endoscopy needed in most patients; if patient actively bleeding and vomiting blood, intubation necessary before endoscopy; antibiotic prophylaxis  —  standard for bacteremia, spontaneous bacte­rial peritonitis, or aspiration (reduces complications); for patient with bleeding from visible varices, banding per­formed; balloon tamponade  —  if patient too unstable for banding; usually sufficient; transjugular intrahepatic portosystemic shunt (TIPS)  —  next step; bridges hepatic vein, usually to right portal vein (stent);  obtain imaging of portal vein to determine whether TIPS possible; if portal vein clotted, TIPS not possible; if patient not stable, perform Doppler ultrasonography in ICU; surgical shunting  —rarely performed; preferred procedure in patient with Child’s class A cirrhosis and no previous bleeding, especially in alcoholic cirrhosis; patient with portal vein thrombosis may require surgical procedure to reroute portal HTN

Nonselective b-blockers: usual next step after patient stabilized in ICU; not much data to support use of selective b- block­ers (eg, metoprolol) in portal HTN;  cirrhotic patient rarely needs propranol >2 times daily; no decrease in portal pressure seen in most patients, so no benefit derived from b-blockers; some believe that patient should receive non­selective b-blocker plus nitrate to maximize response (not tolerated well by most patients); important to band vari­ces to completion (usually 3-4 sessions required); some data suggest that blocker plus banding better than banding alone; TIPS  —  performed in patients with repeated bleeding; 1 mo after TIPS, speaker attempts to determine whether varices shriveled; rarely destination therapy in patient with acute bleeding (does not affect mortality in ad­vanced cirrhosis); benefit in some patients with early reversible disease

Suggested Reading

Bernhard A et al: Influence of bolus consistency and position on esophageal high-resolution manometry findings. Dig Dis Sci 53:1198, 2008; Chiu KC et al: Portal venous flow pattern as a useful tool for predicting esophageal varix bleeding in cirrhotic patients. Dig Dis Sci 50:1170, 2005; Groszmann RJ et al: Portal Hypertension Collaborative Group. Beta-block­ers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 353:2254, 2005; Kim YJ et al: Esophageal varices in cirrhotic patients: evaluation with liver CT. AJR Am J Roentgenol 188:139, 2007; Korsapati H et al: Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis. Gut 58:1056, 2009; Lee SW et al: Independent factors associated with recurrent bleeding in cirrhotic patients with esophageal variceal hemorrhage. Dig Dis Sci 54:1128, 2009; Sarin SK et al: Evaluation of endoscopic variceal ligation (EVL) versus propranolol plus isosorbide mononitrate/nadolol (ISMN) in the prevention of variceal rebleeding: comparison of cirrhotic and noncirrhotic patients. Dig Dis Sci 50:1538, 2005; Scheffer RC et al: Impaired bolus transit across the esophagogastric junction in postfundoplication dyspha­gia. Am J Gastroenterol 100:1677, 2005; Simon D et al: Eosinophilic esophagitis is frequently associated with IgE-medi­ated allergic airway diseases. J Allergy Clin Immunol 115:1090, 2005; Stein ML et al: Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol 118:1312, 2006; Swoger JM et al: Eosinophilic esophagitis: is it all allergies? Mayo Clin Proc 82:1541, 2007; White GN et al: Dysphagia: causes, assessment, treatment, and management. Geriatrics 63:15, 2006; Yoon CJ et al: Transjugular intrahepatic portosystemic shunt for acute variceal bleeding in patients with viral liver cirrhosis: predictors of early mortality. AJR Am J Roentgenol 185:885, 2005; Zimmerman SL et al: Idio­pathic eosinophilic esophagitis in adults: the ringed esophagus. Radiology 236:159, 2005.