2018 Section 6 - Laryngology, Voice Disorders, and Bronchoesophalogy

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Laryngology, Voice Disorders, and Bronchoesophagology

Home Study Course

Hsc Home Study Course

Section 6 November 2018

© 2018 American Academy of Otolaryngology—Head and Neck Surgery Foundation The global leader in optimizing quality ear, nose, and throat patient care

THE HOME STUDY COURSE IN OTOLARYNGOLOGY — HEAD AND NECK SURGERY

SECTION 6

Laryngology, Voice Disorders, and Bronchoesophagology

November 2018

SECTION FACULTY:

Lee M. Akst, MD** David E. Rosow, MD** Paul C. Bryson, MD Brianna K. Crawley, MD Maggie A. Kuhn, MD Matthew C. Mori, MD Julina Ongkasuwan, MD Ashli K. O’Rourke, MS, MD

American Academy of Otolaryngology - Head and Neck Surgery Foundation 1650 Diagonal Road, Alexandria, VA 22314

Section 6 suggested exam deadline: January 2, 2019 Expiration Date: August 6, 2019; CME credit not available after that date

Introduction The Home Study Course is designed to provide relevant and timely clinical information for physicians in training and current practitioners in otolaryngology - head and neck surgery. The course, spanning four sections, allows participants the opportunity to explore current and cutting edge perspectives within each of the core specialty areas of otolaryngology. The Selected Recent Material represents primary fundamentals, evidence-based research, and state of the art technologies in Laryngology, Voice Disorders, and Bronchoesophagology. The scientific literature included in this activity forms the basis of the assessment examination. The number and length of articles selected are limited by editorial production schedules and copyright permission issues, and should not be considered an exhaustive compilation of knowledge on Laryngology, Voice Disorders, and Bronchoesophagology. The Additional Reference Material is provided as an educational supplement to guide individual learning. This material is not included in the course examination and reprints are not provided. Needs Assessment AAO-HNSF’s education activities are designed to improve healthcare provider competence through lifelong learning. The Foundation focuses its education activities on the needs of providers within the specialized scope of practice of otolaryngologists. Emphasis is placed on practice gaps and education needs identified within eight subspecialties. The Home Study Course selects content that addresses these gaps and needs within all subspecialties. Target Audience The primary audience for this activity is physicians and physicians-in-training who specialize in otolaryngology-head and neck surgery. Outcome Objectives 1. Analyze recent findings regarding transoral laser resection of early glottic cancer and compare outcomes to those of patients who undergo radiation. 2. Outline the updated Academy Clinical Practice Guidelines for assessment of hoarseness. 3. Synthesize recent findings regarding the risk factors and etiologies of chronic cough. 4. Discuss the effectiveness of chronic cough treatment with a directed speech language therapy intervention. 5. Evaluate the extent of voice disturbance after thyroid surgery and the efficacy of intraoperative nerve monitoring on improving voice outcomes. 6. Determine the safety profile and potential side effects of long-term proton pump inhibitor therapy for treatment of gastroesophageal reflux disease. 7. Describe the potential use of pepsin as an assay marker for diagnosis of laryngopharyngeal reflux disease. 8. Interpret the finding of Mycobacterium species in the microbiome of patients with idiopathic subglottic stenosis, and the implication on diagnosis and treatment. 9. Evaluate current management strategies for laryngotracheal stenosis, including awake, in- office steroid injections.

Medium Used The Home Study Course is available in electronic or print format. The activity includes a review of outcome objectives, selected scientific literature, and an online self-assessment examination. Method of Physician Participation in the Learning Process The physician learner will read the selected scientific literature, reflect on what they have read, and complete the self-assessment exam. After completing this section, participants should have a greater understanding of Laryngology, Voice Disorders, and Bronchoesophagology as they affect the head and neck area, as well as useful information for clinical application. Accreditation Statement The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Credit Designation The AAO-HNSF designates this enduring material for a maximum of 40.0 AMA PRA Category 1 Credit(s) ™. Physicians should claim credit commensurate with the extent of their participation in the activity. ALL PARTICIPANTS must achieve a post-test score of 70% or higher for a passing completion to be recorded and a transcript to be produced. Residents’ results will be provided to the Training Program Director. PHYSICIANS ONLY : In order to receive Credit for this activity a post-test score of 70% or higher is required . Two retest opportunities will automatically be available if a minimum of 70% is not achieved. Disclosure The American Academy of Otolaryngology Head and Neck Surgery/Foundation (AAO-HNS/F) supports fair and unbiased participation of our volunteers in Academy/Foundation activities. All individuals who may be in a position to control an activity’s content must disclose all relevant financial relationships or disclose that no relevant financial relationships exist. All relevant financial relationships with commercial interests 1 that directly impact and/or might conflict with Academy/Foundation activities must be disclosed. Any real or potential conflicts of interest 2 must be identified, managed, and disclosed to the learners. In addition, disclosure must be made of presentations on drugs or devices, or uses of drugs or devices that have not been approved by the Food and Drug Administration. This policy is intended to openly identify any potential conflict so that participants in an activity are able to form their own judgments about the presentation. [1] A “Commercial interest” is any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. 2 “Conflict of interest” is defined as any real or potential situation that has competing professional or personal interests that would make it difficult to be unbiased. Conflicts of interest occur when an individual has an opportunity to affect education content about products or services of a commercial interest with which they have a financial relationship. A conflict of interest depends on the situation and not on the character of the individual. Estimated time to complete this activity: 40.0 hours

2018 SECTION 6 LARYNGOLOGY, VOICE DISORDERS, AND BRONCHOESOPHAGOLOGY FACULTY

** Co-Chairs: Lee M. Akst, MD, Director, Division of Laryngology and Assistant Professor, Department of Otolaryngology, Johns Hopkins Department of Otolaryngology-Head and Neck Surgery, Baltimore, Maryland. Disclosure: Consultant: Olympus; Honoraria: KayPentax. David E. Rosow, MD, Director, Division of Laryngology and Voice Disorders, Associate Professor, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida. Assistant Professor, Department of Vocal Performance, University of Miami Frost School of Music, Coral Gables, Florida. Disclosure: No relationships to disclose. Faculty: Paul C. Bryson, MD, Director, Cleveland Clinic Voice Center; Head, Section of Laryngology; Assistant Professor, Case Western University Lerner College of Medicine, Cleveland Clinic Department of Otolaryngology-Head and Neck Surgery, Cleveland, OH. Disclosure: Consultant: Fortec Medical; Honoraria: Visual Dx. Brianna K. Crawley, MD, Associate Professor, Loma Linda University, Department of Otolaryngology – Head & Neck Surgery, Loma Linda, California. Disclosure: No relationships to disclose. Maggie A. Kuhn, MD, MAS, Associate Professor, University of California, Davis, Department of Otolaryngology – Head & Neck Surgery, Sacramento, California. Disclosure: No relationships to disclose. Matthew C. Mori, MD, Assistant Professor, Icahn School of Medicine at Mount Sinai, Department of Otolaryngology-Head and Neck Surgery, New York, New York. Disclosure: No relationships to disclose. Julina Ongkasuwan, MD, Associate Professor, Adult and Pediatric Laryngology, Bobby R. Alford Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine; Director, Texas Children’s Hospital Pediatric Voice Clinic, Houston, Texas. Disclosure: No relationships to disclose. Ashli K. O’Rourke, MS, MD, Associate Professor, Evelyn Trammell Institute for Voice and Swallowing, Department Otolaryngology – Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina. Disclosure: Other – Advisory Board Member: Carolina Speech Services; Consultant: Medtronic.

Planner(s): Linda Lee, AAO─HNSF Education Program Manager No relationships to disclose Stephanie Wilson, Stephanie Wilson Consulting, LLC; No relationships to disclose Production Manager Richard V. Smith, MD, chair, AAO-HNSF Education Expert Witness: various legal firms Steering Committee Thomas L. Carroll, MD, chair, AAO-HNSF

Consultant: Pentax Medical; Sofregen Medical.

Laryngology & Bronchoesophagology Education

Expert Witness: various legal firms

Committee

This 2018 Section 6 Home Study Course does not include discussion of off-label uses of drugs or devices which have not been approved by the United States Food and Drug Administration.

Disclaimer The information contained in this activity represents the views of those who created it and does not necessarily represent the official view or recommendations of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

Suggested Section 6 Exam submission deadline; course closes August

January 2, 2019:

6, 2019

EVIDENCE BASED MEDICINE The AAO-HNSF Education Advisory Committee approved the assignment of the appropriate level of evidence to support each clinical and/or scientific journal reference used to authenticate a continuing medical education activity. Noted at the end of each reference, the level of evidence is displayed in this format: [EBM Level 3] .

Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001) Level 1

Randomized 1 controlled trials 2 or a systematic review 3 (meta-analysis 4 ) of randomized controlled trials 5 . Prospective (cohort 6 or outcomes) study 7 with an internal control group or a systematic review of prospective, controlled trials. Retrospective (case-control 8 ) study 9 with an internal control group or a systematic review of retrospective, controlled trials. Case series 10 without an internal control group (retrospective reviews; uncontrolled cohort or outcome studies). Expert opinion without explicit critical appraisal, or recommendation based on physiology/bench research.

Level 2

Level 3

Level 4

Level 5

Two additional ratings to be used for articles that do not fall into the above scale. Articles that are informational only can be rated N/A , and articles that are a review of an article can be rated as Review. All definitions adapted from Glossary of Terms, Evidence Based Emergency Medicine at New York Academy of Medicine at www.ebem.org .

1 A technique which gives every patient an equal chance of being assigned to any particular arm of a controlled clinical trial. 2 Any study which compares two groups by virtue of different therapies or exposures fulfills this definition. 3 A formal review of a focused clinical question based on a comprehensive search strategy and structure critical appraisal. 4 A review of a focused clinical question following rigorous methodological criteria and employing statistical techniques to combine data from independently performed studies on that question. 5 A controlled clinical trial in which the study groups are created through randomizations. 6 This design follows a group of patients, called a “cohort”, over time to determine general outcomes as well as outcomes of different subgroups. 7 Any study done forward in time. This is particularly important in studies on therapy, prognosis or harm, where retrospective studies make hidden biases very likely. 8 This might be considered a randomized controlled trial played backwards. People who get sick or have a bad outcome are identified and “matched” with people who did better. Then, the effects of the therapy or harmful exposure which might have been administered at the start of the trial are evaluated. 9 Any study in which the outcomes have already occurred before the study has begun. 10 This includes single case reports and published case series.

OUTLINE

NOVEMBER 2018, SECTION 6

LARYNGOLOGY, VOICE DISORDERS, AND BRONCHOESOPHAGOLOGY

I. LARYNGOLOGY

A. Early glottic cancer B. Clinical practice guideline for dysphonia C. Laryngeal hypersensitivity D. Voice outcomes after thyroid surgery

II. BRONCHOESOPHAGOLOGY

A. Treatment of laryngopharyngeal reflux B. Microbiome of the upper aerodigestive tract C. Management of laryngotracheal stenosis

TABLE OF CONTENTS Selected Recent Materials - Reproduced in this Study Guide

2018 SECTION 6: Laryngology, Voice Disorders, and Bronchoesophagology

ADDITIONAL REFERENCE MATERIAL.........................................................................i - iii

I.

Laryngology A. Early glottic cancer

Ahmed J, Ibrahim ASG, Freedman LM, Rosow DE. Oncologic outcomes of KTP laser surgery versus radiation for T1 glottic carcinoma. Laryngoscope . 2018; 128(5):1052- 1056. EBM level 4...........................................................................................................1-5 Summary : This retrospective cohort study compared oncologic outcomes for patients (N = 87) with T1 glottic cancer treated with radiation versus transoral KTP laser resection. Recurrence, laryngeal preservation, disease-free survival, and overall survival rates were statistically similar between the groups. The authors conclude that KTP laser ablation is equivalent to primary radiation therapy in oncologic outcomes for T1 glottic squamous cell carcinoma. Fiz I, Mazzola F, Fiz F, et al. Impact of close and positive margins in transoral laser microsurgery for Tis-T2 glottic cancer. Front Oncol . 2017 Oct 16; doi:10.3389/fonc.2017.00245. [eCollection 2017]. EBM level 4................................6-14 Summary : The authors provide a large series of 507 early glottic cancer patients ranging from carcinoma in situ to T2 and assess the impact of positive margins on disease-specific survival (DSS) and recurrence-free survival. The study indicates that close and positive single superficial margins do not affect DSS. By contrast, all types of margin positivity predict the occurrence of relapses, albeit with different likelihood, depending on stage/margin type. Lee HS, Kim JS, Kim SW, et al. Voice outcome according to surgical extent of transoral laser microsurgery for T1 glottic carcinoma. Laryngoscope . 2016; 126(9):2051-2056. EBM level 4..................................................................................................................15-20 Summary : This article evaluates voice outcomes in a group of patients with T1 glottic carcinoma who underwent transoral laser resection of their tumors. The findings reveal that voice may improve with less advanced types of cordectomy (ELS types I-III) and that voice outcomes are worse with advanced types of cordectomy (IV-V) and when there is anterior commissure involvement.

Mehlum CS, Rosenberg T, Groentved AM, et al. Can videostroboscopy predict early glottic cancer? A systematic review and meta-analysis. Laryngoscope . 2016; 126(9):2079‐2084. EBM level N/A.............................................................................21-26 Summary : This meta‐analysis (5 studies, 307 patients) was completed to estimate the diagnostic accuracy of stroboscopy in differentiating early glottic cancer from noninvasive lesions. The sensitivities of stroboscopy within the single studies ranged from 86% to 100%, and specificities ranged from 7% to 93%. The meta‐analysis showed that the sensitivity of the combined results was 0.96 (95% confidence interval [CI]: 0.89-0.98), and the specificity was 0.65 (95% CI: 0.21-0.93). The authors conclude that stroboscopy is able to identify almost all patients with cancer, but only approximately two-thirds of patients with noninvasive lesions are correctly identified as not having cancer. Zeitels SM, Burns JA. Oncologic efficacy of angiolytic KTP laser treatment of early glottic cancer. Ann Otol Rhinol Laryngol . 2014; 123(12):840-846. EBM level 4...........................................................................................................................27-33 Summary : This is a follow up to the original case series published by the authors with additional patients (N = 117) and longer follow‐up (minimum 3 years), allowing further analysis of oncologic efficacy of this technique. Disease control for T1 and T2 lesions was 96% (79/82) and 80% (28/35), respectively. There were 10 recurrences, all treated with radiotherapy. Larynx preservation and survival were achieved in 99% of patients (81/82) with T1 disease and 89% of patients (31/35) with T2 disease. B. Clinical practice guideline for dysphonia Stachler RJ, Francis DO, Schwartz SR, et al. Clinical practice guideline: hoarseness (dysphonia) (update). Otolaryngol Head and Neck Surg . 2018; 158(Suppl 1):S1-S42. EBM level N/A.............................................................................................................34-75 Summary : This AAO evidence-based review of management of dysphonia, focused on both otolaryngologists and primary care physicians, concludes that we should not be treating dysphonia with antibiotics, corticosteroids, proton pump inhibitors, etc, nor ordering imaging studies for the evaluation of dysphonia until vocal fold examination has been done to support the use of any of these approaches. C. Laryngeal hypersensitivity Chamberlain Mitchell SA, Garrod R, Clark L, et al. Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial. Thorax . 2017; 72(2):129-136. EBM level 1b....................76-83 Summary : In this randomized control trial, patients with refractory chronic cough were randomized to a cough-specific speech and language pathology treatment group or a control (general health and wellness counseling sessions) group. Leicester Cough Questionnaire (LCQ) scores improved and cough frequency decreased significantly in the intervention group as compared to control group.

Çolak Y, Nordestgaard BG, Laursen LC, et al. Risk factors for chronic cough among 14,669 individuals from the general population. Chest . 2017; 152(3):563-573. EBM level 2c..........................................................................................................................84-94 Summary : This article presents a large Danish population study of 14,669 patients who completed a survey involving demographics, risk factors, and Leicester Cough Questionnaire (LCQ). It examines individual and community-level risk factors with several interesting findings, including overall chronic cough prevalence of 4%, female gender only a risk factor for nonsmokers (prevalence of female chronic cough patients lower than other studies), and a median LCQ score of 17.3, which is higher than prior studies. This is the first study to determine prevalence and impact of chronic cough in the general population. Francis DO, Slaughter JC, Ates F, et al. Airway hypersensitivity, reflux, and phonation contribute to chronic cough. Clin Gastroenterol Hepatol . 2016; 14(3):378-384. EBM level 2b.......................................................................................................................95-101 Summary : The article presents a blinded cross-sectional study of nonsmoking patients with chronic cough refractory to reflux treatment who underwent 24-hour acoustic recording concurrently with pH-impedance monitoring. Results showed that phonation and reflux events increase rate of coughing. Findings support airway sensitivity as cause of cough with vocal folds as effector. Vertigan AE, Bone SL, Gibson PG. Laryngeal sensory dysfunction in laryngeal hypersensitivity syndrome. Respirology . 2013; 18(6):948-956. EBM level 2.......................................................................................................................102-110 Summary : Laryngeal sensory function is impaired in patients with chronic cough, paradoxical vocal fold movement, globus pharyngeus, and muscle tension dysphonia. This study is the first to quantify sensory dysfunction and identify the extent of overlap between the conditions. It provides a hypothesis for development of further treatments for these conditions. It also provides a useful discussion of laryngeal hypersensitivity as a type of chronic pain syndrome, and discusses a nice work-up and evaluation of these patients. D. Voice outcomes after thyroid surgery Baek SK, Lee K, Oh D, et al. Efficiency of intraoperative neuromonitoring on voice outcomes after thyroid surgery. Auris Nasus Larynx . 2017; 44(5):583-589. EBM level 4.......................................................................................................................111-117 Summary : Baek et al found that among patients who underwent intraoperative neuromonitoring (IONM), there were significantly smaller changes in the fundamental frequency at postoperative 1 month and in the maximum voice pitch of the voice range profile at postoperative 1 week, irrespective of the extent of thyroid surgery. They conclude that IONM during thyroid surgery resulted in better outcomes regarding fundamental frequency and high-pitch voice in the early postoperative period. IONM appears to be an effective method to reduce temporary phonation alteration after thyroid surgery.

Chandrasekhar SS, Randolph GW, Seidman MD, et al. Clinical practice guideline: improving voice outcomes after thyroid surgery. Otolaryngol Head Neck Surg . 2013; 148(6 Suppl):S1-S37. EBM level N/A....................................................................118-154 Summary : This AAO evidence-based review on voice change after thyroid surgery advocates for evaluation of patients with dysphonia both before and after thyroid surgery, among other recommendations.

Lee JC, Breen D, Scott A, et al. Quantitative study of voice dysfunction after thyroidectomy. Surgery . 2016; 160(6):1576-1581. EBM level 4..........................155-160

Summary : Voice quality deteriorates with thyroid surgery despite a functionally intact recurrent laryngeal nerve. While likely multifactorial, the degree of deterioration is related to the extent of the operation and may also be related to the degree of recurrent laryngeal nerve swelling. Spontaneous resolution is expected in the majority of patients. Sinclair CF, Bumpous JM, Haugen BR, et al. Laryngeal examination in thyroid and parathyroid surgery: an American Head and Neck Society consensus statement: AHNS Consensus Statement. Head Neck . 2016; 38(6):811-819. EBM level 3a..............161-169 Summary : This American Head and Neck Society (AHNS) consensus statement discusses the techniques of laryngeal examination for patients undergoing thyroidectomy and parathyroidectomy. It is intended to help guide all clinicians who diagnose or manage adult patients with thyroid disease for whom surgery is indicated, contemplated, or has been performed. This consensus statement concludes that flexible transnasal laryngoscopy is the optimal laryngeal examination technique, with other techniques, including laryngeal ultrasound and stroboscopy, being useful in selected scenarios. Tedla M, Chakrabarti S, Suchankova M, Weickert MO. Voice outcomes after thyroidectomy without superior and recurrent laryngeal nerve injury: VoiSS questionnaire and GRBAS tool assessment. Eur Arch Otorhinolaryngol . 2016; 273(12):4543-4547. EBM level 4............................................................................170-174 Summary : This study looks at GRBAS and VoiSS scores following thyroidectomy in patients without recurrent or superior laryngeal nerve injury and concludes that change in voice is prevalent. Age, TSH level, and reflux are risk factors for voice change. Attwood SE, Ell C, Galmiche JP, et al. Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies. Aliment Pharmacol Ther . 2015; 41(11):1162-1174. EBM level 1..............................................................................................................175-187 Summary : This paper reports findings from two large randomized studies of GERD treatment. The study design is unique in that patients were prospectively randomized to anti-reflux surgery vs. proton pump inhibitor therapy. Over a period of 5 to 12 years, the incidence of serious adverse events did not differ between groups. Some metabolic differences were detected. These studies provide some of the best evidence available on long-term risks of GERD treatment. Though study bias is minimized, the studies were funded by a pharmaceutical company that produces omeprazole and esomeprazole.

II.

Bronchoesophagology A. Treatment of laryngopharyngeal reflux

Calvo-Henriquez C, Ruano-Ravina A, Vaamonde P, et al. Is pepsin a reliable marker of laryngopharyngeal reflux? A systematic review. Otolaryngol Head Neck Surg . 2017; 157(3):385-391. EBM level 2..................................................................................188-194 Summary : This study reviews the recent publications addressing the diagnosis of laryngopharyngeal reflux using various pepsin assays. Results support the utility of pepsin, though the best method of detection has yet to be elucidated. It also highlights the potential problems with sensitivity and specificity that prevent its espousal as a “gold- standard” tool. Francis DO, Patel DA, Sharda R, et al. Patient-reported outcome measures related to laryngopharyngeal reflux: a systematic review of instrument development and validation. Otolaryngol Head Neck Surg . 2016; 155(6):923-935. EBM level 4......................195-207 Summary : In the absence of readily available diagnostic tests, many clinicians rely upon patient-reported outcome (PRO) measures to diagnose laryngopharyngeal reflux and to gauge treatment success. This study critically and systematically examined those outcome measures and found all measures to be deficient to variable degrees. It highlights the need to understand each PRO before applying it in research or clinical decision-making. This study employs investigational methods that do not often appear in otolaryngologic literature. Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol . 2016; 73(4):410-416. EBM level 2....................................................................................208-214 Summary : This article has made a big splash in the lay press. It is a prospective cohort study of 73,679 subjects who take proton pump inhibitors (PPIs) regularly and an internal control group of individuals who do not take PPIs. The authors found an increased risk if dementia in individuals taking PPIs. The hazard ratio was 1.44 (95% CI, 1.36 to 1.52; p < 0.001). Xie Y, Bowe B, Li T, et al. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open . 2017; 7(6):e015735. EBM level 3.....................................................................................215-225 Summary : This a large 5-year longitudinal cohort study using an Veterans Administration (VA) database following patients prescribed proton pump inhibitors (PPIs) and H2 blockers. Their primary outcome measure was death. The authors use several statistical techniques to try to control for the numerous variables to determine if PPIs were an independent risk factor. While there are some mythological questions that remain, the authors determined that they believe that PPI use is associated with an increased risk of death in the VA population.

B. Microbiome of the upper aerodigestive tract Gelbard A, Katsantonis NG, Mizuta M, et al. Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species. Laryngoscope . 2017; 127(1):179-185. EBM level N/A...................................................................................................................226-232 Summary : This article aims to use non-culture–dependent techniques to describe the tracheal microbiome composition in normal and diseased (idiopathic subglottis stenosis and intubation-related laryngotracheal stenosis) states. Furthermore, it seeks to identify specific pathogens associated with these particular disease states through a variety of biochemical and histological techniques in order to consider differences in the pathogenesis of different airway stenosis. Mycobacterium species predominate in idiopathic subglottic stenosis, and peripheral serum samples from test cases demonstrate a specific immune response to Mycobacterium antigen. This suggests a potential role for Mycobacterium infection or the host response to it in the development of idiopathic subglottic stenosis. Summary : The authors of this study used fecal samples to measure the microbiomes using RNA techniques to determine changes in microbiome populations which they believe are attributable to proton pump inhibitor (PPI) use. The authors used both historic data for control as well as isolating 70 twin pairs with discordant PPI use. Ortega O, Sakwinska O, Combremont S, et al. High prevalence of colonization of oral cavity by respiratory pathogens in frail older patients with oropharyngeal dysphagia. Neurogastroenterol Motil . 2015; 27(12):1804-1816. EBM level 4.......................241-253 Summary : The authors aim to further characterize the relationship of swallowing function, bacterial burden, and host immunity in frail, elderly adults who are susceptible to aspiration pneumonia. A number of variables among dysphagic elderly subjects with and without pneumonia as well as elderly subjects without dysphagia are compared. Those subjects with pneumonia have evidence of less swallowing safety. All subjects have similar oral health, and no significant differences among commensurate or pathologic organisms exist. Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut . 2016; 65(5):749-756. EBM level 4.......233-240

Turan M, Ekin S, Ucler R, et al. Effect of inhaled steroids on laryngeal microflora. Acta Otolaryngol . 2016; 136(7):699-702. EBM level 2.................................................254-257

Summary : Using standard microbiology evaluation (Gram staining and catalase tests), the authors sought to understand the effect of inhaled corticosteroids on the laryngeal (epiglottis) microbiome as well as in adjacent pharyngeal areas (oropharynx, vallecula). An abundance of specific organisms (coagulase-negative Staphylococcus , Streptococcus viridans , Candida ) was observed in inhaled steroid users across all sampled sites.

C. Management of laryngotracheal stenosis Franco RA Jr, Husain I, Reder L, Paddle P. Awake serial intralesional steroid injections without surgery as a novel targeted treatment for idiopathic subglottic stenosis. Laryngoscope . 2018; 128(3):610-617. EBM level 4..............................................258-265 Summary : This is a retrospective cohort study examining the records of subjects over a mean of 3 years to determine whether in-office steroid injection into idiopathic subglottic stenosis could improve patients’ airways without surgical intervention. In a group of six patients, the improvement in breathing was sufficient in five of them to avoid surgery. In those with worse disease, operative intervention was initially undertaken, but in-office steroids were then used to decrease the need for further surgery. Gelbard A, Donovan DT, Ongkasuwan J, et al. Disease homogeneity and treatment heterogeneity in idiopathic subglottic stenosis. Laryngoscope . 2016; 126(6):1390-1396. EBM level 4..............................................................................................................266-272 Summary : This publication compiles results from 11 international centers to include almost 500 patients with idiopathic subglottic stenosis and presents their epidemiologic findings and overall treatment outcomes. They found great heterogeneity in treatment algorithms between centers as well as an inverse correlation between recurrences and surgical volume (follow-up averaging 4 to 5 years). Lewis S, Earley M, Rosenfeld R, Silverman J. Systematic review for surgical treatment of adult and adolescent laryngotracheal stenosis. Laryngoscope . 2017; 127(1):191-198. EBM level 4..............................................................................................................273-280 Summary : This systematic review does a good job of highlighting how much remains unknown and the overall inadequacy of the available evidence in the management of this group of disorders. Findings include resection and anastomosis as superior in achieving decannulation and avoiding future surgery, and that the etiology of stenosis affects decannulation rates and the need for further surgery. Prasanna Kumar S, Ravikumar A, Thanka J. Role of topical medication in prevention of post-extubation subglottic stenosis. Indian J Otolaryngol Head Neck Surg . 2017; 69(3):401-408. EBM level N/A...............................................................................281-288 Summary : A rabbit model has been established studying postextubation subglottic stenosis. This study assessed effects of topical mitomycin-C and triamcinolone on postextubation mucosal ulceration, scab, and submucosal thickening/fibrosis. The study was well-designed with appropriate controls. One weakness is that it is an animal study, albeit one that brings more rigorous histopathologic analysis to treatment of postextubation subglottic stenosis.

Shadmehr MB, Abbasidezfouli A, Farzanegan R, et al. The role of systemic steroids in postintubation tracheal stenosis: a randomized clinical trial. Ann Thorac Surg . 2017; 103(1):246-253. EBM level 1..................................................................................289-296 Summary : This paper presents a randomized double-blind clinical trial of 120 postintubation tracheal stenosis patients. It compares long-term, low-dose prednisolone versus placebo for patients requiring repeated bronchial dilation with primary outcomes: days between bronchoscopy, number of patients ultimately requiring airway resection, and length of resected airway. Results showed trends towards significance for the first two outcomes, and statistically significant difference in length of resected airway favoring steroid treatment.

NOVEMBER 2018, SECTION 6 ADDITIONAL REFERENCES

Branco A, Todorovic Fabro A, Gonçalves TM, Garcia Martins RH. Alterations in extracellular matrix composition in the aging larynx. Otolaryngol Head Neck Surg . 2015; 152(2):302-307.

Cha W, Yoon BW, Jang JY, et al. Office-based biopsies for laryngeal lesions: analysis of consecutive 581 cases. Laryngoscope . 2016; 126(11):2513-2519.

Croake DJ, Stemple JC, Uhl T, et al. Reliability of clinical office-based laryngeal electromyography in vocally healthy adults. Ann Otol Rhinol Laryngol . 2014; 123(4):271-278.

D’Anza B, Knight J, Greene JS. Does body mass index predict tracheal airway size? Laryngoscope . 2015; 125(5):1093-1097.

Djukic V, Milovanovic J, Jotic AD, Vukasinovic M. Stroboscopy in detection of laryngeal dysplasia: effectiveness and limitations. J Voice . 2014; 28(2):262.e13-262.e21.

Domer AS, Leonard R, Belafsky PC. Pharyngeal weakness and upper esophageal sphincter opening in patients with unilateral vocal fold immobility. Laryngoscope . 2014; 124(10):2371-2374.

Durvasula VSPB, Shalin SC, Tulunay-Ugur OE, et al. Effects of supramaximal balloon dilatation pressures on adult cricoid and tracheal cartilage: a cadaveric study. Laryngoscope . 2018; 128(6):1304- 1309. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology . 2017; 152(4):706-715.

Gelbard A, Francis DO, Sandulache VC, et al. Causes and consequences of adult laryngotracheal stenosis. Laryngoscope . 2015; 125(5):1137-1143.

Gong H, Shi Y, Xiao X, et al. Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma. Sci Rep . 2017; 7(1):5507.

Hanshew AS, Jetté ME, Rosen SP, Thibeault SL. Integrating the microbiota of the respiratory tract with the unified airway model. Respir Med . 2017; 126:68-74.

Hoffman MR, Coughlin AR, Dailey SH. Serial office-based steroid injections for treatment of idiopathic subglottic stenosis. Laryngoscope . 2017; 127(11):2475-2481.

Jetté ME, Dill-McFarland KA, Hanshew AS, et al. The human laryngeal microbiome: effects of cigarette smoke and reflux. Sci Rep . 2016; 6:doi:10.1038/srep35882.

Jetté ME, Gaumnitz EA, Birchall MA, et al. Correlation between reflux and multichannel intraluminal impedance pH monitoring in untreated volunteers. Laryngoscope . 2014; 124(10):2345-2351.

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The Laryngoscope V C 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Oncologic Outcomes of KTP Laser Surgery Versus Radiation for T1 Glottic Carcinoma

Jamal Ahmed, MD; Ahmed Sherif Gabr Ibrahim, MD; Laura M. Freedman, MD; David E. Rosow, MD

Objectives/Hypothesis: To characterize outcomes for patients who underwent transoral microsurgery with potassium titanyl phosphate (KTP) laser resection of early glottic cancers and to compare outcomes with patients who received external beam radiation therapy. Study Design: Retrospective cohort study. Methods: The history of patients with T1 glottic carcinoma treated with curative primary radiation or transoral KTP laser resection was reviewed. Oncologic outcomes for both radiation and surgery cohorts including disease-free and overall survival were calculated. Results: Eighty-seven patients met inclusion criteria from 2011 to 2016; 47 patients (54%) received primary KTP laser ablation, and 40 patients (46%) received primary external beam radiotherapy. The average length of follow-up was 924 6 529 days in the KTP laser group and 994 6 603 days in the radiation group ( P 5 .26). There were no significant differences between the two treatment groups in terms of medical or demographic variables. There were six recurrences in the KTP laser group (13%), versus six in the radiotherapy group (15%) ( P 5 .77). The laryngeal preservation rate for the cohort of patients who initially received KTP laser treatment was 46 out of 47 patients (98%). Of the cohort that received primary radiation therapy, the laryngeal preservation rate was 36 out of 40 patients (90%, P 5 .18). Disease-free and overall survival were 88% and 98% in the KTP laser cohort and 85% and 95% in the radiation cohort ( P 5 .78, P 5 .56), respectively. Conclusions: KTP laser ablation is a modality equivalent to primary radiation therapy in oncologic outcomes for T1 glottic squamous cell carcinoma. Key Words: Laryngeal cancer, early glottic cancer, laser, radiation therapy, outcomes. Level of Evidence: 4 Laryngoscope , 00:000–000, 2017

INTRODUCTION Laryngeal carcinoma is one of the most common upper aerodigestive tract malignancies, 1,2 and glottic carcinoma is the most common subtype. 3 The incidence of laryngeal carci- noma and deaths from carcinoma is decreasing, likely due to the decreased prevalence of tobacco use. 4 The vast majority of these laryngeal cancers are squamous cell carcinomas in patients with a history of tobacco smoking. 3,5 Many patients present with voice changes or hoarseness in the earliest stages of carcinogenesis, which allows for expeditious evaluation and treatment of many tumors while they are From the Department of Otolaryngology ( J . A ., A . S . G . I ., D . E . R .), University of Miami Miller School of Medicine, Miami, Florida, U.S.A.; Department of Surgical Oncology ( A . S . G . I .), National Cancer Institute, Cairo University, Cairo, Egypt; and the Department of Radiation Oncology ( L . F .), University of Miami Miller School of Medicine, Miami, Florida, U.S.A. Editor’s Note: This Manuscript was accepted for publication July 24, 2017. Presented at the American Bronchoesophagological Association at the Combined Otolaryngology Spring Meetings, San Diego, California, U.S.A., April 26–30, 2017. This work was funded by the Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida, U.S.A. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to David E. Rosow, MD, Department of Otolaryngology–Head and Neck Surgery, Don Soffer Clinical Research Center, 1120 NW 14th Street, 5th Floor, Miami, FL 33136. E-mail: drosow@med.miami.edu

still relatively small. There are multiple options for treating early-stage glottic carcinoma, and these consist of open sur- gery, transoral laser microsurgery, or radiation. For patients who fail radiation, surgical salvage remains an option, rang- ing from focal ablations to total laryngectomy. 6 At present, transoral laser microsurgery (TLM) is the mainstay of surgical therapy for early glottic carci- noma. 7 The benefits of laser resection include improved hemostasis, precise control of depth of ablation, and the ability to repeat therapy while avoiding open neck sur- gery. In addition, primary utilization of TLM allows sav- ing radiation therapy as a valuable salvage therapeutic. Although TLM has historically been performed with a carbon dioxide (CO 2 ) laser, there is a small but growing literature base for the use of potassium titanyl phos- phate (KTP) laser for glottic carcinoma. The KTP laser is primarily absorbed by red pigment, such as hemoglobin, which makes it an excellent instrument for selectively vaporizing tissues that are highly vascular- ized, a process known as selective photoangiolysis. Taking advantage of this property of the KTP laser can allow for effective oncologic resection while minimizing the energy delivered, and therefore causing less collateral tissue dam- age. Given the proven link between angiogenesis and tumor growth, it is understandable that the KTP laser would be an attractive instrument for cancer ablation, and early research has shown acceptable oncologic and voice outcomes similar to those seen with the CO 2 laser. 8–10 This study was

DOI: 10.1002/lary.26853

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in 87 patients who met inclusion criteria, 47 of whom received primary KTP laser ablation and 40 who received primary EBRT. This represented all patients who underwent primary treatment for T1 glottic carci- noma at our institution over the time period studied. Average length of follow-up was 924 6 529 days in the KTP laser group and 994 6 603 days in the radiation group ( P 5 .26). There were no significant differences between the two treatment groups in all demographic variables and comorbidities studied, including average age, gender, average body mass index, alcohol/tobacco use, diabetes, coronary artery disease, chronic obstruc- tive pulmonary disease, gastroesophageal reflux disease, or stroke (data not shown). Both groups had similar pro- portions of patients present with hoarseness, dysphagia, or shortness of breath; the vast majority of patients presented with hoarseness. In addition, both groups had similar proportions of patients with T1a and T1b disease, as well as the presence or absence of anterior commissure involvement (Table I). For the six patients who recurred after KTP-TLM, all were offered a choice of revision surgery versus radiation. Three patients lived a long distance from our institution and chose to undergo radiation therapy closer to home. Two additional patients chose radiation at our institution, for a total of five patients who received successful salvage radiation therapy. The sixth patient underwent a total lar- yngectomy for a large recurrence but died due to progres- sion of disease. The final laryngeal preservation rate for the cohort of patients who initially underwent primary KTP laser resection was 46 out of 47 patients (98%), with an average follow-up of approximately 31 months. In the primary radiation group, 29 patients (73%) received 63 Gy, one (3%) received 64 Gy, six (15%) received 65.25 Gy, three (8%) received 66 Gy, and one (3%) received 68 Gy. There were six recurrences in the radiotherapy group (Table II). Of these patients, four underwent total laryngectomy for the recurrence, and two of these patients died of disease. One patient maintained local control but recurred in the neck; this was successfully treated with neck dissection. The remaining patient underwent two courses of additional KTP laser ablation for two recurrences. Of the cohort that received primary radiation therapy, the laryngeal preservation rate was 36 out of 40 patients (90%, P 5 .18). For the patients who received primary radiation therapy and then recurred, the final laryngeal preservation rate was 33%. For patients who

TABLE I. Disease Characteristics of Both Cohorts of Patients.

KTP-TLM

EBRT

P Value

No.

47

40

—

T1a

36 (77%) 11 (23%)

28 (70%) 12 (30%)

.63

T1b

AC involved

12 (26%)

15 (38%)

.25

AC spared

35 (74%)

25 (62%)

AC 5 anterior commissure; EBRT 5 external beam radiation therapy; KTP 5 potassium titanyl phosphate; TLM 5 transoral laser microsurgery.

undertaken to prove the hypothesis that oncologic outcomes will not be significantly different in patients receiving primary radiation therapy or primary transoral KTP laser resection for T1 glottic carcinomas at a single academic institution.

MATERIALS AND METHODS Patient Selection

Institutional review board approval was granted for a retro- spective chart review of patients aged 18 years and older treated between January 2011 and January 2016 at a single academic ter- tiary referral center for T1a or T1b squamous cell carcinoma of the vocal folds. Treatment for all patients consisted of either pri- mary external beam radiation therapy (EBRT) or KTP-TLM. A choice of either treatment was offered to all patients and was made according to several factors, including patient preference, perceived difficulty of operative microlaryngoscopic exposure, and ability to tolerate general anesthesia. Patients with a prior his- tory of glottic cancer, or any other head and neck malignancy, were excluded. Demographic and clinical data were extracted via chart review and analyzed. Objective vocal parameters were obtained from the surgical group including F0 (fundamental frequency), jitter (a measure of frequency variation), shimmer (a measure of amplitude variation), and noise-harmonic ratio. Sub- jective voice assessment was obtained through pre- and postoper- ative Voice Handicap Index (VHI-10) scores. Oncologic outcomes for both radiation and surgery cohorts including disease-free sur- vival and overall survival were calculated. Statistical Analysis Contingency tables were used to compare categorical varia- bles in the KTP-TLM group versus the EBRT group using the Fisher exact test and v 2 test for trend. Continuous variables were analyzed using Mann-Whitney tests and Student t tests. Oncologic outcomes (disease-free survival and overall survival) were determined using Kaplan-Meier plots for each cohort and both log-rank (Mantel-Cox) test and Gehan-Breslow-Wilcoxon tests. Pre- and postoperative voice parameters were examined using Wilcoxon matched-pairs signed rank test. Prism GraphPad software (GraphPad Software, Inc., La Jolla, CA) was used to analyze data. Statistical significance was determined as P < .05. RESULTS A total of 137 patients were seen at our institution for a diagnosis of T1 glottic cancer over the study period. Of these, 50 patients were excluded from analysis due to being recurrent cases, being upstaged at surgery, having a history of other head and neck malignancy, declining treatment, or having treatment elsewhere. This resulted

TABLE II. Oncologic Outcomes of Both Cohorts of Patients.

KTP-TLM

EBRT

P Value

No.

47

40

—

924 6 529 994 6 603

Follow-up, d

.26

Recurrences

6 (13%)

6 (15%) 4 (10%)

.77 .18

Salvage TL

1 (2%)

Laryngeal preservation rate

98%

95% .18

EBRT 5 external beam radiation therapy; KTP 5 potassium titanyl phosphate; TL 5 total laryngectomy; TLM 5 transoral laser microsurgery.

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