Papers by Randal Paniello
Operative Techniques in Otolaryngology-Head and Neck Surgery, 2012
In laryngeal paralysis, the stiffness of the denervated vocal fold is decreased. This leads to de... more In laryngeal paralysis, the stiffness of the denervated vocal fold is decreased. This leads to deviant vibratory patterns involving 2 asymmetric vocal folds and results in abnormal vocal quality. Follow-up studies of medialization thyroplasty patients have noted that decrement in vocal quality after medialization is often because of continuing vocal fold atrophy. Vocal cord atrophy from denervation injury can be countered by reinnervation. This article reviews the most commonly performed laryngeal reinnervation procedure for unilateral vocal fold paralysis: ansa cervicalis nerve to recurrent laryngeal nerve anastomosis.
Laryngoscope, Jul 18, 2023
Muscle & Nerve, Aug 14, 2023
AGU Fall Meeting Abstracts, Dec 1, 2011
Otolaryngology-Head and Neck Surgery, May 5, 2014
ObjectiveTo determine the etiology, laterality, and time to presentation of unilateral vocal fold... more ObjectiveTo determine the etiology, laterality, and time to presentation of unilateral vocal fold paralysis (UVFP) at a tertiary care institution over 10 years.Study DesignCase series with chart review.SettingAcademic medical center.Subjects and MethodsAll patients seen between 2002 and 2012 by the Department of Otolaryngology at the Washington University School of Medicine (WUSM), with a diagnosis of unilateral vocal fold paralysis, were included. Medical records were reviewed for symptom onset date, presentation date(s), and etiology of UVFP.ResultsOf the patients, 938 met inclusion criteria and were included. In total, 522 patients (55.6%) had UVFP due to surgery; 158 (16.8%) were associated with thyroid/parathyroid surgery, while 364 (38.8%) were due to nonthyroid surgery. Of the patients, 416 (44.4%) had nonsurgical etiologies, 124 (13.2%) had idiopathic UVFP, and 621 (66.2%) had left‐sided UVFP. The diagnosis was more common on the left side in cases of intrathoracic surgeries and malignancies, as expected, but also in idiopathic, carotid endarterectomy, intubation, and skull base tumors. In total, 9.8% of patients presented first to an outside otolaryngologist at a median time of 2.1 months after onset, but these patients presented to WUSM at a median time of 9.5 months. Overall, 70.6% of patients presented to a WUSM otolaryngologist within 3 months of onset.ConclusionIatrogenic injury remains the most common cause of UVFP. Thyroidectomy remains the leading cause of surgery‐related UVFP. Patients are typically seen within 3‐4 months of onset; however, a significant delay exists for those referred to WUSM.
Laryngoscope, 2009
Decreasing the closing speed of the vocal folds can reduce loudness and energy in the higher freq... more Decreasing the closing speed of the vocal folds can reduce loudness and energy in the higher frequency harmonics, resulting in reduced voice quality. Our aim was to study the correlation between higher frequencies and the intraglottal vorticity (which contributes to rapid closing by producing transient negative intraglottal pressures). Using six excised canine larynges (three with symmetric and three with asymmetric, periodic vocal fold motion), intraglottal vorticity was calculated from 2D velocity fields measured using particle imaging velocimetry. There is a strong correlation between intraglottal vorticity and acoustic energy in the higher frequencies; in periodic asymmetric motion, the vorticity and higher frequencies are both reduced. For unilateral vocal fold paralysis, these findings suggest one reason why periodic, asymmetric motion, may produce an abnormal voice. Further study will help determine when and why reinnervation, as opposed to medialization, may result in better voice quality.
Annals of Otology, Rhinology, and Laryngology, Jun 1, 2001
Objectives/Hypothesis: To determine whether the hypoglossal nerve (XII) can serve as a suitable d... more Objectives/Hypothesis: To determine whether the hypoglossal nerve (XII) can serve as a suitable donor for human laryngeal reinnervation. Study Design: Prospective, nonrandomized. Methods: Measurements were made on patients undergoing open neck procedures to determine the length of XII available and that required to perform XII-recurrent laryngeal nerve (RLN) anastomosis. The morbidity of combined XII and RLN injuries was studied using temporary lidocaine block of the ipsilateral XII in patients with unilateral vocal fold paralysis (UVFP). A pilot series of patients with UVFP who underwent XII-RLN reinnervation was evaluated for morbidity of the procedure, and for improvement in voice and swallowing. Results: In 89 necks the average available length of XII was 2 cm less than that needed to reach the larynx, indicating the RLN stump must be at least 3 cm to allow tension-free anastomosis. Twenty-five patients with untreated UVFP underwent temporary lidocaine block of XII; 8 had slight changes in their speech, none had increased aspiration. Nine patients underwent XII-RLN reinnervation. Postoperative speech analysis correlated well with the findings of the temporary lidocaine block of XII. One-year follow-up of five patients showed excellent voice quality, resolution of any preoperative aspiration, and minimal morbidity. Slight adductory movement of the reinnervated vocal fold was seen during tongue thrust. Electromyography confirmed substantial polyphasic action potentials in the thyroarytenoid muscle. Conclusions: The hypoglossal nerve is a very suitable donor for reinnervation of patients with UVFP. There should be enough length for primary XII-RLN anastomosis in most patients. Donor site morbidity is acceptable. Preoperative lidocaine block of XII is a good predictor of actual donor site morbidity and could be used to assess patients undergoing facial-hypoglossal anastomosis as well.
Annals of Otology, Rhinology, and Laryngology, Apr 1, 2000
In this study, the injection of phenol into the true vocal fold was evaluated on a rat model as a... more In this study, the injection of phenol into the true vocal fold was evaluated on a rat model as a possible treatment for adductor spasmodic dysphonia. A 10% phenol solution was injected into the right true vocal fold. Quantitative measurement of vocal fold adductory force showed reduction to 35% of the preinjection value 3 months after injection (p < .05). Qualitative evaluation by videolaryngoscopy demonstrated maintenance of the normal vocal fold range of motion. Histologic studies showed a transient inflammatory infiltrate and myolysis, while the vocal fold mucosa and the cricoarytenoid joints remained undamaged. Further investigation into the potential use of phenol for treating spasmodic dysphonia is warranted.
Auris Nasus Larynx, Oct 1, 2020
To describe a novel surgical therapy for the treatment of medically refractory neuropathic cough,... more To describe a novel surgical therapy for the treatment of medically refractory neuropathic cough, in which carefully selected subjects undergo surgical transection of the internal branch of the superior laryngeal nerve (iSLN). Methods: Subjects with a diagnosis of neuropathic cough, who were not improved after two medication trials, underwent iSLN block with local anesthetic in the office. While anesthetized, they underwent provocative testing to determine whether the nerve block improved their symptoms; if so, a modified barium swallow study (MBSS) was performed to determine whether they still swallowed safely without supraglottic sensation. Those who passed this screening were offered operative iSLN transection. We retrospectively reviewed our results to date. Results: Six subjects (5 females, ages 46-71), with neuropathic cough symptoms for 2-15 years, passed the screening and underwent iSLN transection procedures. At a mean follow-up of 8.2 months, significant symptomatic relief was experienced by 5/6 subjects, with Cough Severity Index (CSI) scores averaging 34.83 ± 6.94 pre-op (range 36-40) and 15.5 ± 11.81 post-op (range 0-29) (p = 0.043). Operative time averaged 49 min (range 30-64). There were no major complications. No subjects experienced post-op aspiration problems. Conclusion: This preliminary data supports iSLN transection as a viable option for subjects with refractory neuropathic cough. Our screening algorithm identifies subjects that would be expected to improve with this procedure and confirms a safe swallow.
Journal of Voice, Oct 1, 2022
Annals of Otology, Rhinology, and Laryngology, Jul 20, 2016
To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease t... more To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease the force of vocal fold adduction, as a potential surgical therapy for patients with adductor spasmodic dysphonia (ADSD). Experimental animal study. A canine laryngeal model was used to assess the acute and sustained efficacy of a lateral cricoarytenoid (LCA) muscle release. A total of 34 canine hemilaryngeal preparations were divided among 7 experimental groups. The LCA muscle was separated from its cricoid cartilage origin via an open, anterior, submucosal approach. The laryngeal adductory pressures (LAP) were assessed pre- and post-muscle release via direct recurrent laryngeal nerve stimulation. Measurements were repeated at 1.5, 3, or 6 months postoperatively. Another study evaluated release of the thyroarytenoid (TA) muscle from its thyroid cartilage origin. Releasing the LCA muscle demonstrated a significant decrease in LAP acutely and was maintained at all 3 time points with the aid of a barrier (P < .05). Without the barrier, the LCA muscle reattached to the cricoid. Acute release of the TA muscle did not significantly decrease the LAP. The proposed LCA release procedure may provide patients with a permanent treatment option for ADSD. However, longer-term studies and human trials are needed.
Springer eBooks, Apr 27, 2006
ABSTRACT
International Journal of Radiation Oncology Biology Physics, Apr 1, 2018
diminish normal tissue toxicity while still treating the dominant risk region for occult tumor sp... more diminish normal tissue toxicity while still treating the dominant risk region for occult tumor spread in the contralateral neck. Materials/Methods: We identified 25 patients with early OPSCC N2c disease, as defined by a single contralateral node, and related this node location to common anatomic landmarks. These were plotted on a representative CT neck scan and used to define anatomic borders of the eCTV. We compared normal tissue complication probabilities (NTCP) for 10 HPV+ OPSCC patients planned with both elective RTOG volumes and eCTV. Results: The eCTV was defined anteriorly by the posterior border of the submandibular gland, posteriorly by the posterior edge of the internal jugular vein, superiorly by 2mm above the C2 transverse foramen, inferiorly by the caudal edge of the cricoid, medially by the internal carotid artery, and laterally by the sternocleidomastoid head. The mean RTOG contralateral neck treatment volume was 253.7cc, while the mean eCTV volume we identified was 101.7cc (one-tailed paired t-test, P<.05). The mean dose predicted to the contralateral parotid gland (cPG) using RTOG volumes and eCTV was 21.0 Gy vs 15.1 Gy, respectively (one-tailed paired t-test, P<.001). The mean NTCP of the cPG was 6.9% calculated using the RTOG volumes, and 3.6% using the eCTV volumes (0.52 relative risk, one-tailed paired t-test, P<.001). Conclusion: A highly predictable localization pattern was found for early contralateral neck nodal positivity in patients with HPV+ OPSCC. Reducing the contralateral neck elective target volume as defined by the eCTV lowered the putative NTCP for the contralateral parotid gland and other normal structures. These data support systematic investigation of target volume reduction in the contralateral N0 neck for HPV+ OPSCC patients in future clinical trials.
American Journal of Otolaryngology, May 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Clinical Cancer Research, 2021
Clinical Oncology, Sep 1, 2019
Aims: Organ preservation, an important goal in the treatment of head and neck squamous cell carci... more Aims: Organ preservation, an important goal in the treatment of head and neck squamous cell carcinoma (HNSCC), may include induction chemotherapy and cisplatin with radiation therapy (CRT). To our knowledge, no reports have directly compared the impact of induction chemotherapy with that of CRT on healthrelated quality of life (HRQOL). Materials and methods: In a phase II trial, we assessed the HRQOL of patients treated with induction chemotherapy followed by CRT. Eligible patients had stage IIIeIV HNSCC. HRQOL questionnaires were administered at baseline, the end of induction (EOI), the end of CRT (EOCRT) and after CRT. Functional Assessment of Cancer Therapy (FACT version 4) assessed HRQOL. We carried out a comparison of changes in HRQOL from baseline to EOI and from EOI to EOCRT. This trial is registered with ClinicalTrials.gov (NCT01566435). Results: Thirty patients were enrolled in the study. Most HRQOL questionnaires were completed (88%). The mean total FACT scores did not differ from baseline to EOI (general: 83.8 versus 79.1, P ¼ 0.08; head and neck: 109.7 versus 105.8, P ¼ 0.33; Total Outcome Index: 69.7 versus 62.3, P ¼ 0.03; respectively, using P 0.01 to adjust for multiple simultaneous tests of differences). However, total FACT scores significantly worsened from EOI to EOCRT (79.1 versus 62.3, P ¼ 0.01; 105.8 versus 74.2, P < 0.01; 62.3 versus 34.2, P ¼ 0.01; respectively). Within domains, the head and neck cancer subscale score did not differ from baseline to EOI (median 28.5 versus 27.0, P ¼ 0.69), but significantly worsened from EOI to EOCRT (27.0 versus 9.5, P < 0.01). Swallowing, oral pain and voice quality improved from baseline to EOI, but worsened from EOI to EOCRT. Physical and functional scores worsened from baseline to EOI and from EOI to EOCRT. The emotional well-being score improved from baseline to EOI but worsened from EOI to EOCRT. Conclusions: Overall, HRQOL did not significantly change from baseline to EOI but dramatically worsened from EOI to EOCRT.
Nature Genetics, Apr 1, 2023
Journal of Clinical Oncology, Jun 1, 2023
6015 Background: Cell cycle deregulation is ubiquitous in HNSCC. In HPV-negative disease, the mos... more 6015 Background: Cell cycle deregulation is ubiquitous in HNSCC. In HPV-negative disease, the most common genomic alteration of cell-cycling included CDKN2A deletions (57%), mutations (27%) or hypermethylation (12%). Selective CDK4/6 inhibition arrested cell cycling and inhibited tumor growth in cell-line and xenograft models of HPV-negative HNSCC, and CDKN2A alterations were predictive of response. An exploratory analysis of a double-blind, randomized, phase 2 trial of patients with HPV-negative recurrent/metastatic HNSCC showed that CDKN2A alterations were associated with better overall survival (OS) with palbociclib and cetuximab vs placebo and cetuximab (median 9.7 vs 4.6 months, HR 0.38). OS was similar between the two arms in patients without CDKN2A alterations. A phase 2 basket trial of patients with CDKN2A-altered head and neck cancers observed that palbociclib resulted in a target lesion decrease in 25% of patients. Collectively, these data warrant further studies to delineate predictive biomarkers of response to selective CDK4/6 inhibitors in HPV-negative HNSCC. Methods: The primary aims of this single-arm, phase 2 trial were to determine the objective response rate (ORR) of HPV-negative, LA-HNSCC to palbociclib, and to correlate responses to somatic CDKN2A alterations. HPV-negative disease was defined as SCC of the larynx, hypopharynx or oral cavity, or SCC of the oropharynx if negative for p16 by IHC and/or high-risk HPV-RNA by ISH. Genome sequencing (FoundationOne CDx/Tempus xT) was performed on tumor tissue obtained before treatment. Patients received palbociclib 125 mg/d orally on days 1-21 of each 28-day cycle. Tumor response was assessed using RECIST 1.1 with CT scans performed pre and post two cycles of palbociclib. Patients then received CRT. A sample size of 24 patients yielded an 80% power if the ORR was ≥38%, using an exact binomial test of one sample proportion comparison with an upper one-sided nominal significance level of 0.05 and null ORR of ≤17%. Results: 24 patients enrolled and completed two cycles of palbociclib: primary site (larynx-15; hypopharynx-4; oropharynx-4, oral cavity-1), clinical stage (III-7; IV-17), and smoking history (yes-23; no-1). The ORR with palbociclib was 41.7%. Best tumor response included: CR (1), PR (9), SD (13), and PD (1). CDKN2A altered disease was identified in 15 patients (62.5%) [mutation: 8, deletion: 7]. Tumor response to palbociclib occurred in 10 of 15 patients (66.7%) with CDKN2A altered disease versus 0 of 9 patients (0%) without CDKN2A altered disease (p=0.002, Fisher’s Exact Test). Conclusions: The primary hypothesis was met: the ORR with palbociclib in HPV-negative, LA-HNSCC was 41.7%. The ORR with palbociclib was significantly higher in CDKN2A altered disease. Clinical trial information: NCT03389477 .
Journal of Clinical Oncology, Jun 1, 2023
Journal of Clinical Oncology, May 20, 2011
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Papers by Randal Paniello