Impact of naturalistic smartphone positioning on acoustic measures of voicea).

Smartphone technology has been used for at-home health monitoring, but there are few available applications (apps) for tracking acoustic measures of voice for those with chronic voice problems. Current apps limit the user by restricting the range of smartphone positions to those that are unnatural and non-interactive. Therefore, we aimed to understand how more natural smartphone positions impacted the accuracy of acoustic measures in comparison to clinically acquired and derived measures. Fifty-six adults (11 vocally healthy, 45 voice disordered, aged 18-80 years) completed voice recordings while holding their smartphones in four different positions (e.g., as if reading from the phone, up to the ear, etc.) while a head-mounted high-quality microphone attached to a handheld acoustic recorder simultaneously captured voice recordings. Comparisons revealed that mean fundamental frequency (Hz), maximum phonation time (s), and cepstral peak prominence (CPP; dB) were not impacted by phone position; however, CPP was significantly lower on smartphone recordings than handheld recordings. Spectral measures (low-to-high spectral ratio, harmonics-to-noise ratio) were impacted by the phone position and the recording device. These results indicate that more natural phone positions can be used to capture specific voice measures, but not all are directly comparable to clinically derived values.

Effect of mandibular tori on glottic exposure during simulated suspension microlaryngoscopy.

OBJECTIVES: Mandibular tori have been identified as a contributing factor in difficult exposure during intubation. However, no investigation has measured the effect of mandibular tori on glottic exposure during suspension microlaryngoscopy (SML). The objective of this study was to measure how the size and location of mandibular tori affect glottic exposure during simulated SML at different thyromental distances. METHODS: Suspension microlaryngoscopy was modeled on an anatomically accurate skull and larynx with thyromental distances between 6 and 12 cm. Mandibular tori were simulated by protruding screws 5 to 15 mm from the lingual aspect of the mandible. The tori were positioned either 15 mm (anterior) or 25 mm (posterior) from the midline of the symphysis. The glottic exposure for the various-size tori in each location was measured by recording the displacement of the glottiscope tip relative to the most anterior exposure achievable without tori. The glottiscope angle relative to the horizontal plane was measured for each condition. RESULTS: Mandibular tori of more than 10 mm had a significant impact on glottic exposure. Displacement of the glottiscope tip ranged from 2 to 9 mm for anteriorly placed tori and from 7 to 29 mm for posteriorly placed tori, with larger tori causing greater displacement. Increasing the thyromental distance increased the posterior glottiscope tip displacement regardless of torus size or location. The glottiscope angle increased with larger tori (12º to 28º), but this angle did not change with increasing thyromental distance. CONCLUSIONS: Larger size and more-posterior location of mandibular tori more significantly reduce glottic exposure during SML. The inner table of the mandible is the most relevant anatomic constraint on glottic exposure, which varies with the presence or absence of mandibular tori independent of thyromental distance.

Tracheal Anastomosis Leaks Across Suture Techniques and Tensions: A Biomechanical Ex Vivo Study.

BACKGROUND: Anastomotic leak after tracheal resection may occur while coughing in the early postoperative period. We investigated the varying effects of suturing technique, stretch, and tension on anastomotic leaks during simulated coughs. METHODS: End-to-end anastomoses were performed using continuous or interrupted sutures on excised porcine larynges. Tracheas were secured to a pressurized system simulating cough forces, submerged in a water bath, and stretched to 1, 2, and 3 cm above baseline. Peak pressure, incomplete cough generation, and observed leakages were recorded. Parameters were analyzed using Analysis of Variance (ANOVA), multiple linear regression, and logistic regression modeling. RESULTS: Peak tension (B = -0.660, p < 0.001) and stretch lengths (B = -0.329, p = 0.006) were associated with variance in peak pressure (R2 = 0.77, F(3,294) = 8.182, p < 0.001). Incomplete coughs increased with higher peak tension (odds ratio [OR] = 15.627, p < 0.001) and stretching to 3 cm above baseline (OR = 4.335, p < 0.007). Similarly, leak occurrences, primarily from the posterior tracheal wall, increased with higher peak tension (OR = 1.787, p < 0.001) and stretching to 3 cm (OR = 2.613, p = 0.017). No significance was identified with suturing technique. CONCLUSION: Interrupted and continuous suture techniques do not differ in anastomotic strength during simulated coughs. Increased peak tracheal tension is associated with a weaker anastomosis, and tracheal stretch to 3 cm was associated with a weaker anastomosis. Our study supports the commonly held clinical belief that, to create a stronger anastomosis, tension should be minimized, and particular attention should be placed at the posterior tracheal wall during closure. LEVEL OF EVIDENCE: N/A, Benchtop study Laryngoscope, 2024.

Voice outcomes for photoangiolytic KTP laser treatment of early glottic cancer.

OBJECTIVES: Surgery and radiotherapy routinely provide high cure rates in treating early glottic cancer. Therefore, key metrics for success are optimal voice outcome and preservation of future cancer treatment options. Remarkably, there is a paucity of pretreatment versus posttreatment voice outcome data. Angiolytic KTP (potassium titanyl phosphate) laser treatment of early glottic cancer with ultranarrow margins was initiated to better preserve vocal function. Given that effective oncological results have been achieved, it was hypothesized that this approach would also result in improved posttreatment measures of vocal function that more closely approximate historical norms than pretreatment values. METHODS: Pretreatment and posttreatment voice outcome data were obtained for 92 patients (64 with T1 cancer and 28 with T2 cancer) who underwent 532-nm KTP laser treatment of early glottic cancer in a study design in which each patient essentially served as his or her own control. The evaluations included objective measures (acoustic and aerodynamic) and patients' self-assessments of vocal function (Voice-Related Quality of Life; V-RQOL). A series of mixed analyses of variance were conducted for all vocal function measures, with tumor stage and depth of invasion as the between-subjects variables and time (presurgery versus postsurgery) as the within-subject variable. RESULTS: There were statistically significant (p < or = 0.05) postoperative improvements for acoustic (perturbation and noise-to-harmonics ratio) and aerodynamic (subglottic pressure and vocal efficiency) measures of vocal function, as well as for V-RQOL assessment. CONCLUSIONS: Comprehensive pretreatment and posttreatment voice measures in a large patient cohort demonstrated that the KTP laser significantly improved postoperative vocal function in patients with early glottic cancer. Furthermore, radiotherapy was preserved as an oncological treatment option.

Salvage endoscopic angiolytic KTP laser treatment of early glottic cancer after failed radiotherapy.

OBJECTIVES: Management of early glottic cancer subsequent to failed radiotherapy is challenging, especially in balancing oncological control and function preservation. Patients frequently have been incentivized against surgical management and thus have undergone radiotherapy as initial treatment. This history compounds the difficulty of discussions about surgical management after recurrence. Typically, endoscopic salvage has less morbidity than transcervical partial laryngectomy and is clearly desirable over total laryngectomy. However, there are appropriate concerns about the efficacy of endoscopic salvage and the overarching impact on larynx preservation and survival. Given our success with endoscopic angiolytic KTP laser treatment of previously nonirradiated T1 and T2 glottic cancers, we examined our results from treating similar-sized lesions after failed radiotherapy. METHODS: We performed a retrospective chart review of 20 patients from our cancer database who had undergone failed radiation therapy elsewhere for early glottic cancer and then underwent endoscopic angiolytic KTP laser treatment. RESULTS: Analysis of the geographic tumor recurrence of the 20 patients revealed T1a N0 M0 cancer in 4 patients, T1b N0 M0 cancer in 1 patient, T2a N0 M0 cancer in 1 patient, and T2b N0 M0 cancer in 14 patients. After KTP laser salvage treatment, 4 patients (20%) had local recurrence (all T2b) and required subsequent total laryngectomy, and 3 of these patients (15%) ultimately died of disease. The remaining 16 patients (80%) were free of disease at least 2 years after endoscopic salvage (average follow-up, 39 months). CONCLUSIONS: Our investigation provides preliminary evidence that angiolytic KTP laser salvage treatment of early glottic cancer is an effective treatment after failed irradiation. Studies with larger cohorts and longer follow-up will be necessary to establish incontrovertible evidence of its efficacy.

Early-Stage Glottic Carcinoma in the United States: Demographics and Treatment Choice.

OBJECTIVE: Limited investigation of factors potentially contributing to treatment choice in early-stage glottic carcinoma (EGC) has been performed with large-scale data. The National Cancer Database (NCDB) represents >72% of all new cancer cases in the United States. We hypothesized that NCDB variables may lend insight into treatment decisions between surgery and radiation for EGC. METHODS: The NCDB was queried for all cases of T1-2  N0  M0 glottic carcinoma from 2004 to 2016. We used multivariable logistic regression analysis to examine factors associated with first-line treatment modality: radiation therapy (RT) versus surgery. All reported odds ratios (OR) were adjusted for age, gender, race, insurance, residence in a metropolitan area, region, and facility volume. RESULTS: 34,991 EGC patients received treatment: 6,687 (19%) surgery; 20,289 (58%) RT; and 8,015 (23%) surgery and RT. OR for receiving RT (vs. surgery alone) were >2 for: more advanced T stage cancers (OR 2.5 [95%CI: 2.3, 2.7]), treatment at non-academic facilities (OR 2.8, [95%CI: 2.6, 3.0]), and shorter travel distances to treatment centers (OR 2.2, [95%CI: 2.0, 2.4]). Surgery was more likely with treatment in the western US, higher income, private insurance, living in a metropolitan (vs. non-metropolitan) area, female gender, older age, and low facility volume. Hispanic ethnicity, education level, and race were not associated with treatment type in the multivariable model. CONCLUSION: Most patients in the NCDB receive first-line treatment with radiation for EGC, and this decision is associated with various tumor, patient, and treatment facility characteristics. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:901-907, 2023.

Comparison Between Custom Smartphone Acoustic Processing Algorithms and Praat in Healthy and Disordered Voices.

OBJECTIVE: The aim of this study was to understand the relationship between temporal and spectral-based acoustic measures derived using Praat and custom smartphone algorithms across patients with a wide range of vocal pathologies. METHODS: Voice samples were collected from 56 adults (11 vocally healthy, 45 dysphonic, aged 18-80 years) performing three speech tasks: (a) sustained vowel, (b) maximum phonation, and (c) the second and third sentences of the Rainbow passage. Data were analyzed to extract mean fundamental frequency (fo), maximum phonation time (MPT), and cepstral peak prominence (CPP) using Praat and our custom smartphone algorithms. Linear regression models were calculated with and without outliers to determine relationships. RESULTS: Statistically significant relationships were found between the smartphone algorithms and Praat for all three measures (r2 = 0.68-0.95, with outliers; r2 = 0.80-0.98, without outliers). An offset between CPP measures was found where Praat values were consistently lower than those computed by the smartphone app. Outlying data were identified and described, and findings indicated that speakers with high levels of clinician-perceived dysphonia resulted in smartphone algorithm errors. CONCLUSIONS: These results suggest that the proposed algorithms can provide measurements comparable to clinically derived values. However, clinicians should take caution when analyzing severely dysphonic voices as the current algorithms show reduced accuracy for measures of mean fo and MPT for these voice types.

A Novel Instrument Holder to Improve Operative Efficiency in Endoscopic Laryngeal and Airway Surgery.

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.

Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis.

OBJECTIVE: To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). METHODS: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses. RESULTS: An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. CONCLUSION: The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3087-3093, 2023.

High-force simulated intubation fails to dislocate cricoarytenoid joint in ex vivo human larynges.

OBJECTIVES: We assessed the likelihood of arytenoid dislocation during intubation through the application of controlled force. METHODS: Six cadaveric human larynges were mounted in an apparatus for simulating forcible collision with the arytenoid complexes. An endotracheal tube tip probe (ETTP) was used to push one arytenoid complex, and a non-slip probe (NSP) was tested on the other. Increasing pressure was applied until the probes either slipped or reached 5 kg of force. Dissection was then performed to assess the integrity of the cricoarytenoid ligament. The forces obtained by pushing an endotracheal tube against an electronic balance were measured to estimate the maximal possible intubating force. RESULTS: None of the ETTP or NSP trials disrupted the cricoarytenoid joint ligaments, and the joint never appeared to be dislocated. The mean maximal forces were 1.8 kg for the ETTP (after which, slippage consistently occurred) and 4.7 kg for the NSP. The mean maximal forces from an endotracheal tube pushed against a scale were 1.5 kg (without stylet) and 4.6 kg (with stylet). CONCLUSIONS: Arytenoid dislocation did not happen, and gross disruption of the joint capsule or ligament did not occur, even when the testing approximated the maximum force achievable under extreme conditions. Endotracheal tube insertion thus seems unlikely to cause arytenoid dislocation.

Subepithelial vocal fold infusion: a useful diagnostic and therapeutic technique.

OBJECTIVES: Preservation of the maximum amount of subepithelial superficial lamina propria (SLP) remains an important goal during microlaryngoscopic surgery of phonatory mucosa. Volume expansion of the SLP (Reinke's space) with subepithelial infusion of saline solution has been widely adopted since its introduction in 1991. This technique has evolved so that it is currently used to assist with determining the depth of vocal fold disease, defining residual pliable SLP, enhancing microsurgical precision, and identifying unrecognized disease. The purpose of this investigation was to examine the indications, methods, and benefits of subepithelial infusion of saline solution as an adjunct technique during phonomicrosurgery. METHODS: In a prospective case series, we collected data on 280 consecutive microlaryngoscopy procedures performed over a 12-month period. Subepithelial infusion of saline solution was included in 178 procedures. RESULTS: New disease was identified in 20 of the 178 patients (scar in 15, sulcus in 4, and a mucosal bridge in 1). The depth of needle placement varied depending on the specific disease: 118 of the 178 infusions were done just below the epithelial basement membrane, and 60 infusions were performed deeper within the SLP, just superficial to the vocal ligament. The infusion technique provided surgical assistance in multiple ways, including identifying residual SLP (130 patients), defining the SLP-lesion interface (65 patients), lifting scar (60 patients),providing tension for cordotomy (47 patients), expanding the SLP volume to protect against laser damage (45 patients), and providing hydrostatic compression of vascular ectasias or varices for photoangiolysis (7 patients). The microlaryngoscopy procedures during which infusion was not performed (102 of 280 procedures) were primarily for nonglottic cancer (46 patients), stenosis (30 patients), or arytenoid granuloma (13 patients). CONCLUSIONS: Subepithelial infusion of the SLP with saline solution is a useful microsurgical adjunct during diagnosis and treatment of phonatory mucosal lesions.

High-speed videoendoscopic analysis of relationships between cepstral-based acoustic measures and voice production mechanisms in patients undergoing phonomicrosurgery.

OBJECTIVES: There is increased interest in using cepstral-based acoustic measures for objective clinical voice assessment because of their apparent advantages over more time-honored methods, but there is a paucity of information about how these newer measures relate to underlying phonatory mechanisms. METHODS: We investigated the relationships between the acoustic cepstral peak magnitude (CPM) and high-speed videoendoscopy (HSV)-based measures of vocal fold phonatory function in 20 subjects who underwent phonomicrosurgery for vocal fold lesions. Acoustic and imaging data were acquired during sustained vowel phonation before and after surgery. RESULTS: The changes in the measures between presurgical and postsurgical assessments showed that the CPM correlated significantly with an HSV-based measure combining fundamental frequency deviation and average speed quotient (r = 0.70; p < 0.001) in a multiple linear regression, and that the variation in the CPM could also be attributed to trading relationships between the HSV-based measures of vibratory phase asymmetry and glottal closure. CONCLUSIONS: These initial results demonstrate that the clinical utility of cepstral-based measures can be enhanced by a better understanding of how these acoustic measures relate to underlying phonatory mechanisms. The CPM seems to integrate information about aperiodicity in vocal fold vibration, the relative speed of glottal closure, and estimates of glottal noise generation.

Safety and dosing of bevacizumab (avastin) for the treatment of recurrent respiratory papillomatosis.

OBJECTIVES: Increasing evidence supports the use of laryngeal injections of the antiangiogenic agent bevacizumab (Avastin) for the adjuvant treatment of recurrent respiratory papillomatosis (RRP). A recent prospective open-label investigation, approved by the US Food and Drug Administration, employing 12.5 mg of sublesional bevacizumab demonstrated single-site efficacy without complications; however, the safety of multiple-site injections and higher dosing has not yet been reported. The primary objective of this study was to report on the safety of increased doses of bevacizumab for the treatment of RRP. METHODS: Two cohorts of adult patients were evaluated. In the first group, a prospective analysis was performed on patients with a diagnosis of laryngeal RRP after t heir participation in th e initial clinical trial with a single-site lowerdose (7.5 to 12.5 mg). They received higher doses of sublesional laryngeal bevacizumab (15 to 50 mg total) with detailed physiologic, hematologic, and serum chemistry measurements performed before and after each bevacizumab injection. A second cohort of patients received sublesional laryngeal injections of bevacizumab (15 to 88 mg total) without physiologic measurements and underwent a retrospective analysis of reported complications. RESULTS: One hundred consecutive laryngeal injection sessions (office, 87; operating room, 13) with bevacizumab were performed in 43 patients, with a mean dose of 30 mg total per treatment (range, 15 to 88 mg). Sixty-three of the 100 sessions were accompanied by KTP laser photoangiolysis of the papilloma prior to bevacizumab injections. Eighteen patients (cohort 1) underwent detailed physiologic assessment, and no dysfunction was observed. There were no local or systemic complications of bevacizumab administration. The second group of 25 patients (cohort 2) also reported no significant local or systemic complications. Neither patient group was observed to have a local wound problem in the larynx. CONCLUSIONS: This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements in pharmacologic concentration and drug delivery will determine the optimal treatment regimens in the future.

Vocal Fold Cyst Formation after Photoangiolytic KTP Laser Treatment of Early Glottic Cancer.

OBJECTIVE: The incidence of post-operative glottic cyst (POGC) formation in patients treated with transoral laser microsurgery with potassium-titanyl-phosphate laser (TLM-KTP) photoablation of early glottic carcinoma (EGC) has not previously been described. METHODS: A retrospective chart review was performed to identify all patients with early glottic cancer who underwent with single-modality TLM-KTP at our institution. Each patient received regular follow up with videostroboscopy for tumor surveillance. New glottic cysts seen on surveillance examinations were noted and their management was documented. RESULTS: A total of 33 patients met inclusion criteria. Eight patients (24%) developed POGC's within the original geographic perimeter of the cancerous vocal fold(s): 6 in the infraglottic region and 2 near the vocal process, at an average of 8 months after their initial cancer surgery. Of these 8 POGC's, 7 were at the periphery of the original tumor distribution and 1 was in the center of it. No POGC's were associated with any change in voice. Four of the 8 POGC's were phonosurgically excised, all without evidence of malignancy on pathology. The remaining 4 were monitored: 2 were stable for an average of 49 months of follow up; the remaining 2 resolved spontaneously by 7 and 31 months after first identification. CONCLUSIONS: POGC's are a frequent sequela of TLM-KTP for EGC. While these results suggest that they are unlikely to represent submucosal recurrences, surgeons should have a low threshold to biopsy if there is clinical concern for such and should counsel patients pre-operatively about the potential for their formation.

Surgical Treatment of Acquired Velopharyngeal Insufficiency in Adults With Dysphagia and Dysphonia.

OBJECTIVES: Velopharyngeal insufficiency (VPI) is a form of velopharyngeal dysfunction caused by abnormal or insufficient anatomy. This process is known to be associated with dysphagia and dysphonia but surgical interventions for these complex patients have not been well studied. The current study characterized a small cohort of adult patients with acquired VPI, dysphonia, and dysphagia, as well as associated surgical interventions. METHODS: A retrospective descriptive case series of 22 (N = 22) adult patients over a 6-year period with acquired VPI and varying degrees of dysphagia and dysphonia was described from a multi-disciplinary voice and swallowing clinic. Perceptual assessment, nasopharyngoscopy, fluoroscopic swallowing assessment, and patient reported outcomes were reviewed to characterize the cohort. RESULTS: VPI etiologies included: stroke (n = 4), head and neck cancer (n = 5), brainstem lesions (n = 5), trauma (n = 5), and other/unknown (n = 3). All 22 patients underwent nasopharyngoscopy and were categorized as having unilateral (n = 13), central (n = 4), or no (n = 5) velopharyngeal deficits. Seventeen patients (77.2%) underwent modified barium swallow studies, revealing that soft palate elevation scored least impaired among patients with no VPI, and most impaired among patients with unilateral VPI deficits. All 22 patients underwent some form of surgical intervention for VPI, with 14 (63.6%) of those patients requiring additional surgical revision. CONCLUSION: This series is one of the first to the authors' knowledge to characterize a cohort of individuals with VPI, dysphagia, and dysphonia and associated surgical interventions.

Local injection of bevacizumab (Avastin) and angiolytic KTP laser treatment of recurrent respiratory papillomatosis of the vocal folds: a prospective study.

OBJECTIVES: Photoangiolytic laser treatment of recurrent respiratory papillomatosis (RRP) is effective, but does not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the adjunctive effect on disease recurrence. Since bevacizumab is a new therapeutic modality for RRP, there were also primary safety objectives to determine whether there was a pegative impact on the voice and whether there were local or systemic complications. METHODS: A prospective open-label investigation was conducted in 20 adult patients with bilateral vocal fold RRP. The patients underwent planned 532-nm pulsed KTP laser photoangiolysis of bilateral glottal disease 4 times with an approximately 6-week interval between procedures. At each planned laser procedure, the vocal fold that on initial presentation had a greater volume of disease also underwent 4 serial sublesional bevacizumab injections (7.5 to 12.5 mg in 0.3 to 0.5 mL). A sham injection with saline solution was administered to the other vocal fold as a control. Disease resolution was compared between subjects' vocal folds, and objective measures of vocal function (acoustic, aerodynamic), as well as patients' self-assessments of vocal function (Voice-Related Quality of Life survey), were obtained. RESULTS: All 20 patients completed the study, and there were no local or systemic complications. After 4 injections, 3 of the 20 patients had no discernible disease in either vocal fold. Of the remaining 17 subjects, 16 had less disease in the bevacizumab-treated vocal fold despite starting with more disease. Only 1 of the 17 had more disease in the bevacizumab-treated vocal fold after 4 injections. Moreover, 7 of the 20 patients (35%) did not require a laser procedure in the vocal fold that had received 4 bevacizumab injections, as compared with 3 of the 20 vocal folds (15%) that were treated with laser alone. All of the vocal function measures displayed statistically significant posttreatment improvements, except for average fundamental frequency in the 3 female patients, in whom it fell below the normal range. CONCLUSIONS: This prospective investigation provided evidence that bevacizumab injections enhanced KTP laser treatment of glottal papillomatosis without systemic or local complications. Coupling the antiangiogenesis agent bevacizumab with KTP laser photoangiolysis is conceptually synergistic and scientifically promising since the mechanisms of action are complementary.

KTP Laser Treatment of Early Glottic Cancer: A Multi-Institutional Retrospective Study.

OBJECTIVES: The primary objectives were to report oncologic outcomes of transoral laser microsurgery with potassium-titanyl-phosphate (KTP) laser (TLM-KTP) ablation of early glottic cancer (EGC). The secondary objectives were to report vocal outcomes and to analyze factors that might influence outcomes. METHODS: A multi-institutional, retrospective analysis of consecutive patients treated for T1 or T2 glottic squamous cell carcinoma undergoing TLM-KTP ablation with at least 2 years of follow-up was performed. Patients with prior radiation or surgery for laryngeal disease were excluded. PRIMARY OUTCOME MEASURES INCLUDED: surgical failures requiring radiation or laryngectomy, disease-specific survival (DSS), and overall survival (OS). Secondary outcome measures included: pre- and postoperative Voice Handicap Index-10 (VHI-10) scores. The effects of smoking status, stage, and anterior commissure involvement on outcomes were analyzed. RESULTS: Overall 88 patients met inclusion criteria (83% male, 79.5% current or former smokers). Mean age was 68 (standard deviation (SD): 12). Mean follow-up was 39.5 months (SD: 15.3). Staging included 50 T1a, 21 T1b, and 20 T2 tumors, including three metachronous second primaries. Radiation and/or laryngectomy avoidance was achieved in 87/88 (98.9%) of patients, inclusive of 24 patients requiring KTP re-treatments. Two patients had biopsy-proven recurrence (2.3%), but only 21 of 24 re-treated patients received a formal biopsy. No patients died from laryngeal cancer. DSS and OS were 100% and 92.3%, respectively. The mean VHI-10 scores were 19.3 preoperatively, 3.8 at 6-months postop, and 3.8 at 2-years postop. Smokers had a longer interval to re-treatment (P = .03), patients with T2 lesions had a shorter interval to re-treatment (0.02), and patients with T2 lesions presented with worse initial VHI-10 scores (0.002). CONCLUSIONS: A multi-institutional, retrospective case series of TLM-KTP ablation of EGC demonstrated excellent oncologic outcomes when close surveillance and proactive re-treatments were utilized. Disease-specific survival, overall survival, and vocal function were excellent. Additional studies are necessary to further analyze the merits and risks of this treatment approach.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Atypical Laryngeal Infections: Localized Lesions from Unusual Organisms May Simulate Malignancy.

OBJECTIVE: The identification of rare sources of laryngeal infection in immunocompetent patients. Recovered organisms were Mycobacterium tuberculosis (laryngeal tuberculosis [LTB]), Mycobacterium fortuitum (laryngeal Mycobacterium fortuitum [LMF]), and Blastomyces dermatiditis (laryngeal blastomycosis [LB]). METHOD: Single institution retrospective case series of three patients over a 2.5-year period and review of the literature on laryngeal infections by three atypical organisms. RESULTS: Three patients presented with hoarseness and cough; one additionally had throat pain (LTB). Indirect laryngoscopy demonstrated diffuse laryngeal ulceration (LTB, LMF) and an exophytic, contiguous glottic mass (LB). Direct microlaryngoscopic biopsies and cultures established the diagnoses, including a frozen section in one case (LB), which prevented a simultaneously planned surgical resection. Appropriate antimicrobial therapy yielded dramatic laryngeal and corresponding vocal improvement, for which we provide unique photo and audio documentation. In the last 10 years, fewer than 500 cases of LTB have been reported in the English language medical literature, principally outside the United States. To date, there have been reports of only 34 LB and no cases of LMF. CONCLUSION: Atypical infections of the larynx may be localized and mimic laryngeal cancer on endoscopy. Tissue examination as well as microbiologic samples are diagnostic and complementary.

New mouse model for studying laryngeal transplantation.

OBJECTIVES: Laryngeal transplantation research has been studied in various animal models. For in-depth, immunology-based transplantation research, however, a thoroughly studied animal model must exist. The purpose of this study was to develop a reliable surgical technique in mice to serve as a model for further study of laryngeal transplantation. METHODS: Heterotopic laryngeal transplantation was attempted in 15 immunocompetent mice by use of modifications of previously described techniques established in rats. RESULTS: Various microvascular techniques were used that led to 8 successful transplants (of 15) with patent vascularity at the time of sacrifice. The first 7 attempts at transplantation were unsuccessful because of technical difficulties related to vessel size, soft tissue traumatic injury, and venous congestion. Subsequently, 8 transplantation procedures were successfully performed after modifications of the surgical technique. CONCLUSIONS: This pilot study describes the reproducible surgical techniques performed in using mice for studying laryngeal transplantation. Mice are cost-effective and immunologically well studied, and are thus ideal for further laryngeal transplantation research.