Mainstream Cigarette Smoke Impacts the Mouse Vocal Fold Epithelium and Mucus Barrier.

OBJECTIVES/HYPOTHESIS: Cigarette smoke (CS) is a primary risk factor for the development of numerous benign and malignant laryngeal diseases. The epithelium and mucus lining the vocal folds (VF) are the first barriers against CS. The primary objective of this study was to investigate epithelial and mucus barrier changes in the mouse laryngeal mucosa upon exposure to subacute CS. The secondary objective was to compare mucus barrier changes in mice and human smokers and nonsmokers. Study Design Animal model. METHODS: Mice were exposed to CS for 4 weeks for 4 hours (N = 12, high dose [HD]) or 1 hour (N = 12, low dose [LD]) per day. Air-exposed mice were used as a control group (N = 10). Larynges were harvested and VF epithelial barrier integrity was evaluated including cellular proliferation and expression of cell junctions. We also investigated mucus production by examining mucus cell area and mucin expression in mice and human smokers and nonsmokers. RESULTS: HD CS increased VF epithelial cellular proliferation but did not alter the expression of cell junctions. HD CS also induced hypertrophy of the mucus-producing submucosal glands. However, only LD CS increased MUC5AC gene expression. MUC5AC staining appeared elevated in laryngeal specimens from smokers, but this was not significant as compared to nonsmokers. CONCLUSIONS: These findings help us identify potential adaptive mechanisms to CS exposure as well as set the foundation for further study of key aspects of epithelial and mucus barrier integrity that may be implicated in laryngeal disease development following prolonged smoking. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2530-2539, 2021.

Operative and Conservative Management of Laryngeal Contact Granuloma: A Network Analysis and Systematic Review.

OBJECTIVE: Laryngeal contact granuloma is a disease of benign hypertrophic granulation tissue at the medial side of vocal process. Numerous studies of conservative and surgical management have reported effectiveness, yet optimal treatment has not been standardized. We compared primary and secondary outcomes of conservative and surgical treatment using endoscopic grading, Voice Handicap Index-10 (VHI-10), maximum phonation time (MPT), and recurrence rate. METHODS: We performed literature searches of MEDLINE, PubMed, and EMBASE from November 1985 to October 2017, with randomized controlled trials and case control studies of at least three months follow-up as the inclusion criteria. Outcomes included laryngoscopic findings, MPT, and VHI-10. Data regarding study design, outcome analysis, follow-up time, and disease remission were systematically collected. RESULTS: A total of 1069 patients were abstracted from 19 papers. With conservative treatment, 98% of patients' laryngeal granuloma resolved within three months, and 84% for the surgical group. There was a decrease in VHI-10 of 2.69 (95% credible interval (CI) -9.52 to 3.82) and 6.48 (95% CI -15.00 to 1.94) for conservative and surgical management, respectively. MPT improvement was 1.27 s (95% CI: 2.03-5.84) for conservative treatment and 5.02 s (95% CI: 0.78-8.07) for surgical. For all 19 studies, absolute recurrence risk for control, conservative, and surgical measures were respectively 4%, 16%, and 29%. CONCLUSIONS: Most patients treated conservatively or surgically alone responded to treatment, but conservative management was favored. VHI-10 and MPT improvement in surgical patients were noted, but only the latter was statistically significant. In regard to recurrence, conservative management had better outcome than surgical. Taken together, the results suggest that minimally symptomatic granulomas have higher response rate and lower recurrence risk when treated conservatively, while larger, symptomatic granulomas may favor surgical excision followed by medical management to reduce risk of recurrence.

Vocal Hygiene in Collegiate Singers-Does Formal Training Relate to Practices?

BACKGROUND: Vocal hygiene is vitally important for protecting vocal quality and promoting vocal longevity. It includes adequate hydration, avoidance of environmental irritants, and refraining from phonotraumatic behaviors such as screaming, excessive talking, and throat clearing. Formal singing training in addition to enhancing singing techniques, is also assumed to promote good vocal hygiene. Consequently, we investigated whether collegiate singers with formal training are more likely to practice good vocal hygiene habits than untrained collegiate singers. METHODS: We completed a prospective cohort study, where collegiate singers at Stanford University were voluntarily enrolled in an annual vocal health clinic. Full laryngeal exams were performed and demographic information, formal vocal training status, and information on vocal hygiene habits were obtained through questionnaires. The results were then analyzed by grouping singers as "untrained" if less than 1 year of formal training, and "trained" if greater than a year. RESULTS: A total of 82 singers were included for analysis, with 49 (59.8%) having greater than one year of formal training. Trained singers were more likely to employ a primary musical singing style of classical or operatic singing compared to untrained singers who were more likely to utilize "R&B" (P < 0.001). No significant differences were found between groups for hydration practices (P = 0.20), caffeine consumption (P = 0.73), warm up practices (P = 0.08), and phonotraumatic behaviors. Alcohol consumption, smoking tobacco, marijuana, e-cigarette usage was similar between groups. Overall, 11% of our sample reported intermittent less than daily marijuana use, with one singer reporting daily consumption. None of the singers in this sample used e-cigarettes. These rates are noticeably lower than the agematched United States population. Perceptions of cigarettes, marijuana, electronic cigarettes, alcohol, and caffeine were also the same between groups, with the vast majority of singers perceiving these agents as harmful to the voice (64%-100% depending on the agent). No laryngeal pathology was identified during laryngeal examination of any singers. CONCLUSIONS: Vocal hygiene habits are similar between trained and untrained collegiate singers. This likely relates to a desire for vocal longevity irrespective of prior training. This may dispel the long-held assumption that formal training was necessary to develop good vocal habits. We do however, present a very homogenous, highly educated sample of collegiate singers from Stanford University, having significantly less at-risk behavior than their aged-matched counterparts in the general US population. A lack of laryngeal pathology despite extensive vocal demands may also be reflective of good vocal hygiene habits.

Early Injection Laryngoplasty After Surgery: 30 Cases and Proposed Aspiration Assessment Protocol.

Vocal fold movement impairment may significantly compromise postoperative recovery and quality of life of patients following thoracic or cardiothoracic surgery or prolonged intubation. The literature is limited and there is no standard screening protocol for the optimal postoperative swallowing and aspiration evaluations. We performed retrospective review of adult patients undergoing early vocal fold (VF) injection laryngoplasty for acute postoperative Vocal fold movement impairment (<30 days) that had both pre- and postinjection speech language pathologist (SLP) performed swallowing/aspiration evaluations. Records were reviewed for demographics, clinical characteristics, procedural details, and short-term outcome measures of oral intake. In total, 30 patients were included, and had data on swallowing/aspiration studies before and after the VF injection laryngoplasty. Most of the patients were injected within 5 days following the laryngologist evaluation and within 14 days following the iatrogenic recurrent laryngeal nerve injury (23/30, 76.7%). The majority of patients were injected at the bedside by awake transcutaneous injection (22/30, 73.3%), six patients were injected in the operating room under general anesthesia, and two at the outpatient clinic. Pre- and postinjection SLP evaluations included clinical bedside assessment or instrumental evaluation. Following VF injection laryngoplasty, oral diet advancement was noted in 81.8% of the patients that were nil per os before the injection (18/22). No complications were noted. In conclusions, acute VFMI following surgery requires immediate diagnosis and therapeutic strategy to minimize postoperative complications and to overcome impairments in the voice, swallow, and cough. Otolaryngology-SLP interdisciplinary aspiration and swallowing assessment protocol is proposed based on our experience and an extensive literature review.

The Clinical Course of Idiopathic Bilateral Vocal Fold Motion Impairment in Adults: Case Series and Review of the Literature.

AIM: Steps for assessment and successful management of bilateral vocal fold motion impairment (VFMI) are (1) recognition of its presence, (2) identifying the etiology and factors restricting vocal fold motion, (3) evaluation of airway patency, and (4) establishing a management plan. No large series documenting the course and outcome of adult idiopathic bilateral VFMI has been published within the past 15 years. METHODS: Retrospective chart review of adult patients with idiopathic bilateral VFMI at a tertiary academic center. A diagnosis was established if history, physical examination with laryngoscopy, and initial imaging excluded a cause. Records were reviewed for demographics, clinical characteristics, surgical intervention details, and length of follow-up. RESULTS: Nine adult patients with idiopathic bilateral VFMI were identified. There were five males and four females with a mean age of 59.6 years. The mean follow-up period was 54.4 months (range, 6-111 months). Upon presentation to our laryngology service, three patients were advised observation, three patients were advised to undergo urgent tracheostomy, and three patients were advised to undergo elective surgery for airway management. By the end of the follow-up period, only four patients (4/9, 44.4%) were tracheostomy dependent, one of them was lost to follow-up after tracheostomy tub downsizing for decannulation. CONCLUSIONS: To our best knowledge, this is the largest series so far of adult patients with idiopathic bilateral VFMI. Conservative treatment can be considered as an alternative to surgery in select cases.

Autologous fibroblasts for vocal scars and age-related atrophy: A randomized clinical trial.

OBJECTIVES/HYPOTHESIS: To assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA). STUDY DESIGN: Randomized, double-blinded, placebo-controlled, multi-institutional, phase II trial. METHODS: ACFs were expanded from punch biopsies of the postauricular skin in each subject; randomization was 2:1 (treatment vs. placebo). Three injections of 1-2 × 107 cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice. RESULTS: Fifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed. CONCLUSIONS: In this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP. LEVEL OF EVIDENCE: 1 Laryngoscope, 130:2650-2658, 2020.

Tracheal Stenosis Because of Wegener Granulomatosis Misdiagnosed as Asthma.

We describe a patient with Wegener granulomatosis whose complaint of wheezing was incorrectly attributed to asthma. Anesthesiologists must recognize that tracheal stenosis is extremely common in Wegener granulomatosis and can mimic other causes of wheezing.

Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology.

Tremulous voice is a characteristic feature of a multitude of movement disorders, but when it occurs in individuals diagnosed with essential tremor, it is referred to as essential vocal tremor (EVT). For individuals with EVT, their tremulous voice is associated with significant social embarrassment and in severe cases may result in the discontinuation of employment and hobbies. Management of EVT is extremely difficult, and current behavioral and medical interventions for vocal tremor result in suboptimal outcomes. Deep brain stimulation (DBS) has been proposed as a potential therapeutic avenue for EVT, but few studies can be identified that have systematically examined improvements in EVT following DBS. The authors describe a case of awake bilateral DBS targeting the ventral intermediate nucleus for a patient suffering from severe voice and arm tremor. They also present their comprehensive, multidisciplinary methodology for definitive treatment of EVT via DBS. To the authors' knowledge, this is the first time comprehensive intraoperative voice evaluation has been used to guide microelectrode/stimulator placement, as well as the first time that standard pre- and post-DBS assessments have been conducted, demonstrating the efficacy of this tailored DBS approach.

Transoral robotic surgery for the management of head and neck cancer: a preliminary experience.

BACKGROUND: The aim of this prospective study was to determine the technical feasibility, safety, and efficacy of transoral robotic surgery (TORS) for a variety of malignant head and neck lesions. METHODS: From April 2007 to November 2007, 20 patients were enrolled in an institutional review board-approved prospective trial using the daVinci surgical robot. Inclusion criteria for the study consisted of adults with early head and neck cancer involving the oral cavity, oropharynx, hypopharynx, and larynx. RESULTS: Twenty patients were included in this study. In 2 cases, access to the tumor was inadequate and the procedure was terminated. In all 18 cases, negative resection margins were achieved. Intraoral reconstruction was performed in 8 patients. Fifteen of 18 patients underwent concomitant unilateral (n = 10) or bilateral (n = 5) selective neck dissections. None of the patients required tracheotomy and there were no intraoperative or postoperative complications. The average setup time was 54.6 minutes (range, 140-20 minutes), with a precipitous decrease in the setup time as the study progressed. CONCLUSION: TORS is a safe, feasible, and minimally invasive alternative to classic open surgery or endoscopic transoral laser surgery in patients with early cancer of the head and neck. With increasing experience, surgical setup as well as operative time will continue to decrease.

Transoral robotic surgery using a carbon dioxide flexible laser for tumors of the upper aerodigestive tract.

OBJECTIVE: To determine the safety, feasibility, and efficacy of coupling transoral robotic technology with the flexible carbon dioxide (CO2) laser for various tumors of the oropharynx and supraglottic larynx. STUDY DESIGN: Prospective, pilot trial. METHODS: Eight patients were enrolled in an IRB-approved prospective trial for transoral robotic surgery with the aid of the flexible CO2 laser. RESULTS: Seven male patients with early carcinoma of the oropharynx or larynx successfully underwent tumor extirpation with the transoral robot and the flexible CO2 laser. We were unable to gain access to the supraglottic larynx in one female patient. The final pathology revealed seven patients with squamous cell carcinoma and one patient with adenoid cystic carcinoma. The flexible CO2 laser provided fine incisions with excellent hemostasis and minimal peripheral tissue injury. Additionally, the laser provided an excellent tool for raising pharyngeal flaps for reconstruction of the oropharynx. CONCLUSION: The flexible CO2 laser offers a unique advantage of precise incisions and may provide a valuable tool for both tumor extirpation and the creation of flaps for transoral robotic reconstruction.

Transoral robotic surgery using an image guidance system.

OBJECTIVES: To describe a novel technique using the image guidance system for transoral robotic surgery of the pharyngeal and parapharyngeal spaces. STUDY DESIGN: Case series presentation. METHODS: Three cases of oropharyngeal and pharyngeal space lesions are reviewed for presentation, workup, and original management. RESULTS: Final pathology of a vascular malformation, an acinic cell adenocarcinoma, and a squamous cell carcinoma were located and minimally invasively removed by a transoral robotic approach with the aid of image guidance. No complications or recurrences were observed on an average of 7 month follow-up. CONCLUSIONS: Transoral robotic surgery using an image guidance system seems safe and effective in assisting dissection.

Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma.

OBJECTIVES: Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic acid (RNA) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. We previously demonstrated recombinant VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV-IL12) to have significant antitumor effects against squamous cell carcinoma (SCC) in a murine model. Here we evaluate the potential to combine a potent chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve efficacy. STUDY DESIGN: In vitro, three SCC cell lines were tested using rVSV-F and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In an orthotopic floor of mouth murine SCC model, intratumoral injections of virus combined with systemic cisplatin were tested for tumor control and animal survival. RESULTS: In vitro, virus and cisplatin combination demonstrated rapid replication and enhanced tumor cell kill. Human keratinocytes were unaffected by virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better tumor control (P = .06) and survival (P = .024) than combination therapy. CONCLUSIONS: Addition of cisplatin did not affect the ability of either virus to replicate in or kill murine SCC cells in vitro. In vivo, combination therapy enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity. Combination therapy may provide useful treatment for SCC with the development of more efficient viral vectors in combination with different chemotherapy agents or immunostimulatory agents.