Managing Diseases of the Larynx and Esophagus

Educational Objectives

The goal of this program is to update clinicians on current trends in office-based laryngology and management of Barrett’s esophagus. After hearing and assimilating this program, the clinician will be better able to:

Describe several techniques for injection of the vocal cords.

Recognize the 2 major types of spasmodic dysphonia, as well less frequently seen types.

Administer botulinum toxin injections to treat spasmodic dysphonia, laryngeal papillomatosis, and other laryngeal disorders.

Discuss current techniques for diagnosing high- and low-grade dysplasia and Barrett’s esophagus.

Use radiofrequency ablation for treatment of Barrett’s esophagus.

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. Koman­duri is a consultant for TAP Pharmaceuticals and a consultant and speaker for Boston Scientific. Dr. Berke and the planning committee reporte nothing to disclose

Acknowledgements

Dr. Berke spoke at the Annual Clinical Conference of the Kansas City Society of Ophthalmology and Otolaryngology, held January 9-10, 2009, in Kansas City, MO, and sponsored by the Kansas City Society of Ophthalmology and Otolaryngology. Dr. Komanduri was recorded at Annual Symposium on Endoscopic Therapies for Airway and Esophageal Disorders, held September 12-13, 2008, in Chicago, IL, and sponsored by the Northwestern University Feinberg School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Office-based Laryngology

Gerald S. Berke, MD, Professor and Chief, Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles

Objective and subjective measures for evaluating larynx

Imaging: image seen on television camera “a sophisticated shadow”; unreliable

Acoustic measures: difficult to relate to physiology; sig-nificance unclear

Aerodynamic functions: picture of airflow through glottis under revision; now appears to resemble cyclone, with associated twists and eddies

Perceptual: probably best measure; listening to patient’s voice may be most accurate evaluation; drawback  —subjective

True importance of evaluation: documentation; clinical experience more important for diagnosis and management

General principles: time most important element in management; refers to time before problem onset and time elapsed since onset; otolaryngologist may be drawn into publicity if patient public figure; treatment often involves some combination of psychologic counseling, medical therapy, and surgery; procedure chosen less important than physician’s experience with it; most important is honest assessment of problem and which intervention needed; clear communication with patient essential; goal to return patient to what patient and physician consider functional vocal use

Problem underlying many issues in laryngology: mismatches between pulmonary expiratory pressure and laryn­geal closing forces; insufficient laryngeal closing for pulmonary expiratory pressure (glottal insufficiency) com­monly seen

Injection techniques

Point-touch technique: transthyroid cartilage injection with 27-gauge needle; requires no lidocaine (few pain fibers on thyroid cartilage or muscle; discomfort minimal if needle remains deep to those structures)

Trans-cartilaginous technique: requires steep learning curve; speaker places finger in cricothyroid membrane to identify inferior border of thyroid cartilage; puts needle through skin until it contacts that border; holds needle to stabilize it, then pushes through thyroid cartilage to inner perichondrium; can then inject material into vocal cord

Right-angle technique: often necessary for men, who have calcified cartilage; speaker inserts needle, finds infe­rior border of thyroid cartilage, advances needle slightly; then bends needle 90^o so it can enter larynx under perichondrium, which permits injection of material into vocal cord

Material injected: collagen; speaker uses 0.25 to 0.50 mL for transthyroid injection, 1 to 2 mL if going inferior

Indications: acute vocal cord paralysis; poor surgical candidate; glottal insufficiency (injection may improve vocal fold contour); however, returns diminish after 5 to 6 injections; after injection, have patient cough to distribute collagen throughout muscular compartment of vocal fold

Patient satisfaction: high; those with severe glottal insufficiency with minimal dysarthria (often seen in Parkinson’s disease) derive greatest benefit

Other injectable material: calcium hydroxyapatite microspheres (Radiesse; requires 23-gauge needle; lasts longer than collagen); hyaluronic acid (Restylane)

Spasmodic dysphonia: laryngeal resistance too high for pulmonary expiratory pressure; baseline tone increased, so larynx closes higher than pulmonary expiratory pressure; periodic spasms cause voice to break; diagnosis based on strained strangled speech with voice breaks; voice improves with heavy emotion (limbic system involvement)

Types: adduction  —  classic type; abduction  —  delayed closure of vocal cords when going from unvoiced to voiced phoneme (eg,  voice falters when saying “help”); patients sometimes learn to compensate; other types include muscular tension (functional) and psychogenic

Etiology: genetic predisposition; often triggered by  injury (eg, bad cold [or other viral illness], emotional distress); imaging studies suggest brain involvement

Treatment (adductor type): value of speech therapy limited; recurrent laryngeal nerve section rarely performed to­day; denervation–reinnervation surgery effective in selected cases; botulinum toxin injections effective in office-based practice; laryngeal framework surgery (not recommended)

Botulinum toxin A (Botox) injection: speaker uses point-touch technique; most patients women with noncalcified cartilage, which facilitates transcartilaginous approach; inject as low as possible to enter thyroarytenoid muscle; works on motor end plate of muscle, which is under perichondrium; transcartilaginous technique puts botulinum toxin near motor end plate; each bottle contains 100 U; speaker dilutes with 4 mL saline for final dilution of 2.5 U/0.1 mL; typical injected bolus consists of 0.2 to 0.3 mL; average dose 1 U (ranges from 1/64 U to 10-15 U, de­pending on patient)

For abductor dysphonia: toxin injected into posterior cricoarytenoid or cricothyroid muscle; speaker uses fibro­scope to guide him through cricothyroid membrane to back wall of cricoid cartilage; speaker does not use topical anesthesia

Duration of benefit: 3 to 6 mo, depending on dose; larger the dose, longer the duration, but more side effects

Other indications for botulinum toxin injection: granuloma  —botulinum toxin may be sole treatment or adjuvant to surgery; speaker typically administers 7 to 12 U on affected side; also injects contralateral side to prevent other cord from compensating; vocal cord nodules  —  inject directly into muscular compartment; polyps  —  also re­spond; cysts  —  do not respond to botulinum toxin due to presence of cyst wall, which requires removal; some ev­idence supports use in treatment of vocal cord paralysis or paresis; muscular tension dysphonia and pain  —  benefits of injections may diminish as patients become habituated to botulinum toxin; “singing dystonia”  —  rare form of spasmodic dysphonia; occurs in professional singers; tightness in voice may develop after several years of singing professionally; botulinum toxin effective treatment; postsurgical voice rest  —  speaker applies at time of surgery when necessary; laryngospasm  —  most patients respond to treatment of reflux, underlying lung dis­ease (if any), and anxiety; insufficient for small group of patients; in those cases, botulinum toxin “actually quite efficacious”; Tourette’s syndrome  —effective, although mechanism unclear

Laryngeal papillomatosis: cidofovir (Vistide) approved for treating cytomegalovirus (CMV) retinitis in HIV-posi­tive patients; also seems effective against papillomavirus; resolves papillomatous lesions when injected directly into them; can be injected into larynx using point-touch technique; concentrates in gametes, and may have malig­nant potential; speaker does not administer to people of reproductive age; response requires 3 injections at 3-wk in­tervals, with total dose of 0.5 to 1 mL, full strength; indole-3-carbinol  —  active ingredient in cruciferous vegetables; efficacy »25%; speaker also uses as supplement for treating laryngeal papillomatosis

Distal chip technology: short endoscopes with camera chips on end now available; have side channels for inserting biopsy forceps and laser fibers; permits same-day, in-office viewing of laryngeal lesion, taking biopsy, and sending it for analysis; orientation fixed-image, but images as clear as those obtained with rigid scope; easily damaged, and takes »20 min to clean

Laser technology: speaker uses pulse-dye laser (580 nm); light absorbed by red blood cells; permits in-office treat­ment of lesions, eg, papillomas, leukoplakia; lidocaine topical anesthesia

“Super cart”: consists of photography unit, including monitor and digital video camera; costs »$55  000

Barrett’s Esophagus: Novel Management
Approaches

Srinadh Komanduri, MD, MS, Assistant Professor, Department of Medicine, Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL

Risk for adenocarcinoma: as high as 2% in some surveillance studies; risk for low-grade dysplasia 16% in some studies; in prospective multicenter study of 783 patients, annual progression to low-grade dysplasia 2.7%, and to adenocarcinoma with high-grade dysplasia, 1.6%

Challenges: determining who will progress to high-grade dysplasia or cancer; optimal biopsy technique; interob­server variability for dysplasia; surveillance increases patient anxiety and not cost-effective; cancer management (outcomes poor)

Hiatal hernia size and length of Barrett’s esophagus (BE): in retrospective study of 88 patients with BE, speaker and colleagues found that 87% of patients with long-segment BE had hiatal hernia; currently, controversy over whether to repair hernia after ablating BE

Endoscopic ultrasonography (EUS) in patients with BE and high-grade dysplasia: in study of 84 patients (62 of whom underwent EUS), test altered management in only 1.6% of cases; caveat  —  perform EUS before endoscopic management to detect deeper infiltration of lesions

Diagnostic endoscopic mucosal resection (EMR): in study of 14 patients in whom biopsy and EMR compared, EMR led to 27% of patients changing from high-grade dysplasia to intramucosal carcinoma or adenocarcinoma; 36% were downstaged from high-grade to low-grade dysplasia; diagnosis for remaining 36% remained high-grade dysplasia; conclusion  —  EMR offers another sampling method when biopsies insufficient

Jumbo biopsy forceps: speaker and colleagues studied 20 patients with BE; with forceps, obtained samples of dou­ble width, depth, and surface area of conventional biopsies; previously undetected dysplasia observed in 6 patients

Treatment: most effective therapies eliminate mucosal element with least damage to submucosa; radiofrequency ab­lation (RFA) goes to uniform depth below mucosa; eliminates operator error (computer-controlled); cryotherapy  —  in one study of 14 patients, cryotherapy showed 90% efficacy in treating high-grade dysplasia and 75% efficacy in treating intramucosal cancer; in later study of 77 patients, same authors found that 52% experienced mild side ef­fects (eg, chest pain, odynophagia, dysphagia); 3 developed strictures; one had gastric perforation; conclusion  —  randomized controlled trials (RCTs) still needed

Radiofrequency ablation: available systems include balloon-based system, with balloon and catheter passed through endoscope; tailored to circumference of patient’s esophagus; focal ablation  —  for treating patients with short-segment disease; RFA and focal ablation can be used together; when examining data, key to have end point in mind (eg, complete response [all biopsies negative for dysplasia and intestinal metaplasia]); anything less than that considered intermediate response;  RCT  —  43 patients with high-grade dysplasia; in intent-to-treat analysis, RFA associated with complete response in »80%; complete response in 91% of patients in per-protocol analysis, compared to 12% of sham-treated patients

Goal of ablation: to eliminate risk for recurrence as well as current dysplasia; also unclear whether nodules can be resected, followed by ablation of flat dysplastic areas; in study of 31 patients who underwent EMR, followed by RFA of residual disease, 97% of patients had complete response at 12 mo; one patient had perforation of mucosal resection and intramucosal cancer; 4 patients experienced transient dysphagia; one biopsy showed subsquamous nondysplastic intramucosal cancer; intermediate responders  —  in Ablation of Intestinal Metaplasia Containing Dysplasia (AIM trial),  17% of patients classified as intermediate responders; they had multifocal dysplasias and long-segment BE; for such patients, surgery may be more appropriate than endoscopic therapy

Impact of RFA on quality of life: among patients with dysplasia, quality of life improved significantly if response complete (alleviated fears of developing cancer); no significant effect among intermediate responders

Comparison with photodynamic therapy: RFA associated with better outcomes and fewer strictures

Effect on functional integrity of esophagus: no evidence of stricturing or narrowing on final endoscopy; no change in functional luminal impedance planimetry, manometry, and inner diameter after RFA; no change in lower esophageal sphincter pressure

Recent case: 63-yr-old woman with poorly controlled reflux for 10 yr; had BE with distal mass, extensive BE and high-grade dysplasia within mass lesion; patient refused surgery and insisted on endoscopy; speaker recommends that patients always see surgeon and endoscopist before deciding on treatment; patient found to have 3-cm polyp composed entirely of adenocarcinoma in situ, with rare foci of intramucosal invasion; no submucosal extension; submucosal basal edge cauterized, leaving patient free of tumor; biopsies of residual BE also showed flat high-grade dysplasia; patient still refused surgery and underwent RFA instead; showed complete response at 12 mo

Conclusions: yearly incidence of adenocarcinoma from BE, 0.5%; incidence of high-grade dysplasia from BE, 1.3% to 1.6%; RFA currently considered safest, most effective therapy (more knowledge of cryotherapy needed); should be considered effective for all patients with BE, although not necessarily indicated for all patients with nondysplas­tic BE; endoscopic therapy for BE with early neoplasia (high-grade or intramucosal cancer) effective for selected patients; optimal endoluminal therapy involves combination of mucosal resection and RFA; identification of mo­lecular markers necessary to identify patients at highest risk of developing cancer; markers should be eliminated by ablation; can then stop surveillance postablation (makes technologies cost-effective)

Suggested Reading

Belafsky PC et al: Muscle tension dysphonia as a sign of underlying glottal insufficiency. Otolaryngol Head Neck Surg 127:448, 2002; Cannito MP et al: Vocal aging and adductor spasmodic dysphonia: response to botulinum toxin injection. Clin Interv Aging 3:131, 2008; Cantarella G et al: Botulinum toxin injection and airflow stability in spasmodic dysphonia. Otolaryngol Head Neck Surg 134:419, 2006; Deurloo JA et al: Adults with corrected oesophageal atresia: is oesophageal function associated with complaints and/or quality of life? Pediatr Surg Int 24:537, 2008; Dumot JA, Greenwald BD: Ar­gon plasma coagulation, bipolar cautery, and cryotherapy: ABC’s of ablative techniques. Endoscopy 40:1026, 2008; Kimura M et al: Collagen injection as a supplement to arytenoids adduction for vocal fold paralysis. Ann Otol Rhinol Lar­yngol 117:430, 2008; Li YM et al: A systematic review and meta-analysis of the treatment for Barrett’s esophagus.  Dig Dis Sci 53:2837, 2008; Rees CJ et al: Cost savings of unsedated office-based laser surgery for laryngeal papillomas. Ann Otol Rhinol Laryngol 116:45, 2007; Shaheen NJ, Richter JE: Barrett’s oesophagus. Lancet 373:850, 2009; Sharma P et al: Dysplasia and cancer in a large multicenter cohort of patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 4:566, 2006; Sharma VK et al: A prospective pilot trial of ablation of Barrett’s esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system). Endoscopy 40:380, 2008.