Management

1. Evaluation of dysphagia 2. Dilation methods: pros and cons CSGNA Fall into GI Conference 3. Specific disease examples Evaluation and Management of 1. Dysphagia 2. Achalasia 3. Eosinophilic 4. Refractory strictures Ikuo Hirano, MD Division Northwestern University Medical School

Dysphagia Dysphagia localized to neck, nasal regurgitation, Dysphagia localized to : aspiration, associated ENT chest or neck, food symptoms impaction Motility Disorders

Oropharyngeal Esophageal . Achalasia Dysphagia Dysphagia . Diffuse Solid & Liquid Solid Dysphagia Dysphagia . Scleroderma . Polymyositis Motility Structural

Esophageal Dysphagia Structural Etiologies Diagnostic Testing for . Schatzki ring • Upper GI Series/Esophagram/Barium swallow . • Endoscopy . Peptic stricture • Esophageal manometry . Iatrogenic (radiation, surgery, • Esophageal impedance manometry endoscopic therapy) • Impedance planimetry . Esophageal neoplasm • Endoscopic ultrasonography . Caustic injury . Esophageal diverticula . Esophageal web . Congenital esophageal stenosis

1 Fluoroscopy UGI Study

0 15 Seconds 1.5 8.5 3.35.06.6 13. 0

Esophageal Manometry High resolution manometry Swallow mmHg 150 0 Pharynx 140 Upper esophageal sphincter 5 120

100 10

80 15 Esophageal Cm 60 20

40 25 30 20 Lower esophageal sphincter 10 30 0 35 Stomach 20 seconds LES deglutitive relaxation

Predilation Considerations Predilation Considerations Stricture characteristics A. Pre Procedure Esophagram 1. Proximal vs distal location Complex strictures (radiation, surgery) 2. Long vs short stricture B. Intraoperative Fluoroscopy 3. Estimated stricture diameter Tight stricture that scope cannot traverse; 4. Active mucosal inflammation/ulceration Angulation 5. Concomitant fistula/diverticulum Pneumatic dilation Patient characteristics C. Choice of Equipment (1 mm=3 Fr) 1. Comorbidities. Can patient tolerate complication 1. Maloney: 2. Anticoagulation (bleeding ~4/1000) PRO: Blind, Tactile, Reusable 3. Antibiotics (endocarditis prophylaxis if high risk) CON: Blind passage, Axial + Radial force

2 Predilation Considerations 2. Savary: “Rule of Threes” PRO: Wire-guidance, Reliable diameter, Reusable, No more than 3 consecutive dilations once Some tactile sensation resistance is encountered CON: Axial+radial force, patient comfort 3. Hydrostatic Balloon (TTC,TTS, CRE): Eminence and not evidence based PRO: Pt tolerance, Axial, +/- wire, variable diameter & length, visualize results of each successive dilation Based on passage of Maloney dilators that have CON: cost, long strictures, no tactile sensation best tactile response 4. Pneumatic Balloon: Achalasia, Post fundoplication dysphagia Fixed diameter (3,3.5,4 cm) D. Steroid injection for refractory stricture

3 Case Presentation Schatzki Ring A 62 yo male presents to the ER at 1 am complaining that a piece of meat is trapped in • Described by Schatzki & Gary and by his throat. He states that while eating a late Ingelfinger & Kramer in 1953 dinner at a local restaurant, a piece of his • Localized to esophageal squamocolumnar steak “did not go down” (he points at his mid junction and almost invariably coexist with a sternum). He tried to wash down the meat hiatal with water but vomited only the water. This • Found in 4-15% (mean 10%) of radiographic same problem has been happening a few studies. Autopsy study by Goyal reported a times a year for several years. prevalence of 9%

Dysphagia vs Ring Diameter Schatzki ring 3 mm

12 mm

20 mm Repeated dysphagia

Isolated dysphagia

No dysphagia

40 mm Schatzki, AJR 1963

Schatzki’s Ring

4 Schatzki’s Ring Case Presentation • Primary Treatment: 57 yo female referred for evaluation of dysphagia. – Maloney, Savary or balloon dilator. – Most commonly 50-51 Fr (17 mm) • Alternative Tx: • Onset of dysphagia 6 months ago. – Disruption of ring with cold biopsy forceps in 4 quadrants • Both liquids and solids • Long-term follow up following dilatation with 46-58Fr dilator (Eckardt DDS 1992) • Localizes to his lower sternal region – 68% of patients are free of dysphagia at 1 year • Frequent regurgitation of food / saliva – 35% at 2 years • Nocturnal coughing/aspiration • PPI Therapy may prevent recurrence (Sgouros Am J Gastro 2005) • 8# weight loss – Recurrence 47% with omeprazole vs 7% with placebo at 3 years

Achalasia

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High Resolution Manometry in Achalasia Swallow Therapy of Achalasia mmHg 100 0 Pharynx 90 Upper esophageal sphincter • Smooth muscle relaxants 5 80 • Botulinum toxin 70 10 • Pneumatic dilation Failed esophageal peristalsis 60 15 • Per oral endoscopic myotomy (POEM) 50 Cm • Esophageal stent 40 20 • Percutaneous gastrostomy tube 30 25 20 • Heller myotomy Lower esophageal sphincter 10 30 5 0 35 Stomach -10 20 seconds Failed LES deglutitive relaxation

5 Boston Scientific Rigiflex Pneumatic dilation 3.0, 3.5, 4.0 cm diameters

Timed barium swallow Pooled Estimates of Response Rates of Achalasia Treatments

Before Therapy Total Weighted mean Weighted Weighted n response mean mean p±SE % follow-up perforation Botulinum toxin 638 78 ± 33 1 mo NA 412 58 ± 36 6 mo 225 49 ± 23 12 mo

Pneumatic dilation 374 85 ± 30 20 mo 2.6 After (Rigiflex)

Heller myotomy Thoracotomy 1221 84 ± 20 5 yr NA Laparotomy 732 85 ± 18 7.6 yr NA Laparoscopy 365 91 ± 13 1.4 yr NA

Boeckxstaens N Engl J Med 2011 Boeckxstaens N Engl J Med 2011

6 Case Presentation • 42 year old male presents with 12 years of intermittent dysphagia for solids that localizes to his mid sternum. Symptoms have been progressive; now occurring on a daily basis. He has had repeated food impactions after eating meat or bread that last up to 1 hour. He was seen in the ER on 2 occasions for endoscopic disimpaction. Effectiveness of pneumatic dilation is comparable It takes the patient over an hour to complete his meals. to laparoscopic Heller myotomy IF allow for He is embarrassed when he needs to leave the table repeated dilations and accept risk of esophageal during meals to vomit up food that he cannot swallow. perforation The patient was previously diagnosed with GERD and esophageal spasm. PMH includes childhood asthma and allergic rhinitis.

Boeckxstaens N Engl J Med 2011

Eosinophilic Esophagitis 2011 EoE is increasing over past 2 decades in both children and adults worldwide EoE is a clinicopathologic disease Olmstead County, MN (peds/adults) Olten County, Switzerland • Clinically, EoE is characterized by symptoms related to esophageal dysfunction • Pathologically, 1 or more biopsy specimens must show eosinophil-predominant inflammation. With few exceptions, 15 eos/hpf is considered a minimum threshold for the diagnosis of EoE Hamilton County, OH (peds) Denmark • The disease is isolated to the esophagus, and other causes of esophageal eosinophilia should be excluded

Liacouras et al. Eosinophilic Esophagitis Updated Consensus Recommendation. J Allergy Clin Immunol 2011 Prasad Clin Gastro Hepatol 2009; Hruz J Allergy Clin Immunol 2011; DeBrosse J Allergy Clin Immunol 2010; Dellon Aliment Pharm Ther 2015

Epidemiology of EoE in US Health insurance database 2009-11 of 11.5 million; Eosinophilic Esophagitis Prevalence based on ICD9 (530.13) 57/100,000 Clinical Features in Adults

• Male predominant ~70% • Age at diagnosis: 35-40 • Atopy (asthma, allergic rhinitis, atopic dermatitis): ~70% • Primary symptoms: dysphagia, food impaction • Secondary symptoms: heartburn, • Symptom duration prior to diagnosis: 5 years

Dellon Clin Gastro Hep 2014; 12 (4): 589

7 Etiology of Dysphagia The 2 am “Wake up” Call! Retrospective Study 1371 Adults Undergoing EGD for dysphagia

1999 2009

EoE identified in 11-55% of adults with food impaction GERD GERD

Desai Furuta Gastrointest Endosc 2005;61:795 EoE Gonsalves Sanger Zhang Hirano Am J Gastro 2006;101, S66 Kerlin Jones Remedios Campbell J Clin Gastro 2007;41:256 Byrne Peterson Fang Dig Dis Sci 2007; 52: 717 Sengupta Lembo Aliment Pharm Therap 2015; 42; 91

Hirano Am J Gastro 2016 Kidambi, Toto, Hirano World J Gastro 2012

Role of Endoscopy in EoE EoE Endoscopic Reference Score (EREFS) Grade 0 Grade 1 Grade 2 Grade 3 Classify and grade severity of characteristic findings of Edema (loss vascular markings) Edema, Rings, Exudates, Furrows, Strictures (EREFS) Grade 0: Distinct vascularity Grade 1: Decreased Grade 2: Absent Rings (trachealization) Grade 0: None Grade 1: Mild (ridges) Grade 2: Moderate (distinct rings) Grade 3: Severe (not pass scope) Exudate (white plaques) Grade 0: None Grade 1: Mild (<10% surface area) Grade 2: Severe (>10% surface area) Furrows (vertical lines) Grade 0: None Grade 1: Mild Normal Eosinophilic Esophagitis Grade 2: Severe (depth) Stricture Grade 0: Absent Grade 1: Present Hirano Gut. 2013 Hirano Moy Heckman Thomas Gonsalves Achem. Gut. 2012.

Complications of EoE: EoE: A Conceptual Model of Clinical Subtypes Narrow caliber esophagus Based On Inflammation and Tissue Remodeling

Normal EoE inflammation EoE inflammation EoE Fibrosis + Fibrosis

EGD . .

Histo

Dilation Medical/Diet Therapy Hirano Aceves Gastro Clin North Am 2014;43(2):297-316. Hirano Aceves Gastro Clin North Am 2014;43(2):297-316.

8 Suggested Algorithm for Management 3 D’s of Treatment for EoE Of Eosinophilic Esophagitis • Drugs Suspected EoE – Topical steroids Symptom relief & PPI x 8 wks – Systemic steroids Normal histology > 15 Eos/hpf – Leukotriene antagonists (montelukast) EGD with Bx – Mast cell stabilizers (cromolyn sodium) “PPI Responsive Esophageal EoE – Immunomodulators (CRTH2 antagonist, azathioprine) Eosinophilia” (EoE vs GERD) Topical steroid – Biologics (anti IL5, anti IL13, anti TNF, anti IgE) Dietary therapy Persistent Symptoms and Pathology • Dietary Therapy EGD with Bx – Empiric elimination diet Persistent dysphagia Symptom relief & – Allergy testing directed elimination diet Elimination diet with stricture Normal histology – Elemental diet ↑ Dose topical Systemic steroid Esophageal Consider Maintenance Therapy • Dilation (Endoscopic therapy) Biologic therapy ? dilation

Hirano. Eosinophilic Esophagitis (Liacouras Ed). 2011

Esophageal Dilation in EoE Prior to 2008 Esophageal Dilation in EoE 2012: High risk of Esophageal Complications Low risk of Esophageal Complications 8 cases; 3 dilations 474 dilations 1 perforation with EGD 0 perforations

5 dilations 5 large lacerations 70 dilations with EGD or dilation 0 perforations

1 dilation 1 perforation 15 dilations 0 perforations

6 dilations 3 perforations 293 dilations 3 perforations

Esophageal Dilation Does Not Affect the Esophageal Dilation in EoE: Effectiveness, Underlying Esophageal Inflammatory Safety and Impact on Underlying Process Inflammation Dilation without anti-eosinophil therapy • Retrospective study of 474 dilations in 207 adults • 63 patients treated with dilation alone • 93% of patients reported slight or no dysphagia after Pre-Dilation 150 Post-Dilation dilation 121 104 • Esophageal diameter increased from 11 mm pre to 16 mm 100 post dilation • 3 mm incremental dilation per session; median 2 sessions 50 per patient (range 1-13) 0

• Median duration symptom improvement: 15 mos hpf / eosinophil Peak (n=63) • No perforations

Schoepfer AM, et al. Am J Gastroenterol 2010;105:1062-70 Schoepfer AM, et al. Am J Gastroenterol 2010;105:1062-70

9 Esophageal Dilation in EoE: Chest Pain Esophageal Dilation in EoE: Retrospective Analysis of 474 dilations in 207 patients Dilation in EoE has a high degree of patient acceptance Chest pain noted in 7% of patients based on chart review based on patient survey (n=42) Chest pain reported by 74% of patients based on survey

38% of patients experienced moderate to severe post dilation pain lasting less than 4 days in most

Schoepfer AM, et al. Am J Gastroenterol 2010;105:1062-70 Schoepfer AM, et al. Am J Gastroenterol 2010;105:1062-70

Case Presentation Refractory Esophageal Strictures • 16 year old man with onset of severe dysphagia • Proposed Definition (Kochman GIE 2005) for solids of all consistencies following a several – Refractory: Inability to successfully establish week hospitalization for complicated diameter of 14 mm during 5 sessions at 2-week . intervals – Recurrent: Inability to maintain luminal diameter • Local GI EGD demonstrated a severe 3-4 mm for 4 weeks once the target of 14 mm achieved stricture at 20-37 cm. TTS dilation x 4 to 12 mm • Most common etiologies: without benefit – Radiation – Caustic ingestion – Peptic – Surgical anastomosis – Narrow caliber esophagus (EoE)

Siersema Wijkerslooth Gastroint Endosc 2009

Refractory Esophageal Strictures Suggested Algorithm for Management Treatment Options Of Refractory Esophageal Strictures • Repeated dilation Benign – Bougie (Maloney, Savary) – TTS Balloon Esophageal dilation Symptom relief • Intralesional injection (steroid, mitomycin C) • Strictureplasty – Needle-knife “Refractory” Stricture – Endoscopic scissor Rule out esophageal inflammation (LP, EoE, bullous), esophageal dysmotility, oropharyngeal dysphagia – Argon Plasma Coagulation (APC) • Stent therapy – Advantages: Long-term, continuous dilation – Disadvantages: migration, chest pain, durability Dilation with Strictureplasty Serial Esophageal • Self bougienage intralesional steroid Dilations stent • Surgery

Siersema Wijkerslooth Gastroint Endosc 2009

10 Refractory Esophageal Strictures Refractory Esophageal Strictures Intralesional steroid injection Esophageal Stents • First used by Holder in 1969 • Used by dermatology: keloid, burns • Theoretically reduces collagen and fibrin deposition • Most commonly triamcinolone 40-80 mg injection

• PC-SEMS: partially-covered metallic • Biodegradable • FC-SEMS: fully-covered metallic • SEPS: fully-covered plastic

De Wijkerslooth, Siersema, Am J Gastroenterol 2011;106:2080. Siersema Wijkerslooth Gastroint Endosc 2009

16 yo M with refractory mid-distal stricture 20-37 Refractory Esophageal Strictures cm. Failed 4 dilations OSH and 4 dilations NMH Esophageal Stents for Benign Stricture with steroids. Alimaxx • Conceptual advantages for benign strictures – Temporary (usu 4-12 weeks), continuous, gradual dilation to allow for stricture remodeling • Practical disadvantages • Migration (25-50%) • Chest pain • Durability of response • Bleeding

Van Halsema World J Gastrointest Endosc 2015 De Wijkerslooth, Siersema, Am J Gastroenterol 2011;106:2080 Siersema Wijkerslooth Gastroint Endosc 2009 Siersema Wijkerslooth Gastroint Endosc 2009

Stents for Benign Esophageal Stricture Stents for Benign Esophageal Stricture Pooled analysis of 232 patients with refractory strictures Pooled analysis of 232 patients with refractory strictures n (%) n (%) Stricture etiology Stricture etiology Anastomotic 69 (30) Anastomotic 69 (30) Peptic 58 (25) Peptic 58 (25) Radiation 36 (16) Radiation 36 (16) Caustic 29 (13) Caustic 29 (13) Technical success Given risksTechnical and success uncertain sustained benefits, Overall 229 (98.7) Overall 229 (98.7) Fully covered SEMS 85 (100) use of esophagealFully covered stenting SEMS for85 benign (100) strictures SEPS 67 (95.7) shouldSEPS be individualized.67 (95.7) Biodegradable 77 (100) Biodegradable 77 (100) Clinical success ClinicalRandomized success trials awaited. Overall 56 (24.2) Overall 56 (24.2) Fully covered SEMS 12 (14.1) Fully covered SEMS 12 (14.1) SEPS 19 (27.1) SEPS 19 (27.1) Biodegradable 25 (32.9) Biodegradable 25 (32.9)

Van Halsema World J Gastrointest Endosc 2015 Van Halsema World J Gastrointest Endosc 2015

11 Management of Esophageal Strictures

. Steroid injection and stents may reduce frequency of dilation for benign stricture . Esophageal stents are an option for refractory strictures but sustained resolution in < 25% . Pneumatic dilation is highly effective for treatment of achalasia and equivalent to surgical myotomy IF allow for aggressive dilation protocol . Esophageal dilation is safe and effective for esophageal strictures in eosinophilic esophagitis

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