The Global Experience of Laryngeal Transplantation: Series of Eleven Patients in Three Continents.

BACKGROUND: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss. OBJECTIVE: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally. METHODOLOGY: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited. RESULTS: After a minimum of 24 months follow-up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy-dependent by 6 months and all had normal or near-normal swallowing by the end of year two after transplantation. Median follow-up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months. CONCLUSIONS: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end-stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Partners of persons with severe swallowing dysfunction have significantly reduced mental health.

INTRODUCTION: Dysphagia can result in malnutrition, dehydration, social isolation, depression, pneumonia, pulmonary abscess, and death. The effect of dysphagia on the health and quality of life (QOL) of the life partners of persons with dysphagia is uncertain. We hypothesize that the partners of individuals with significant dysphagia will experience a significant reduction in quality of life. PURPOSE: To evaluate the QOL of the significant others of persons with swallowing dysfunction. METHODOLOGY: Persons with significant swallowing dysfunction (defined as EAT10® > 10) and their significant others were prospectively administered the 10-item Eating Assessment Tool (EAT10®) patient-reported outcome measure and the 12-item SF quality of life instrument (SF12). Summary data from the 8 mean health domains were compared between patients and their significant others. Mean scores for each domain are calibrated at 50, and a score below 47 implies significantly diminished QOL for a particular domain. RESULTS: Twenty-three couples were evaluated. The mean ± SD EAT10 score for persons with significant dysphagia was 21 ± 7; mean EAT10 for their significant others or for couples in the control group was 0.3 ± 0.8. The mean physical health composite score (PCS) was significantly lower for patients with dysphagia compared to their significant others (39.1 ± 10 and 46.2 ± 11, respectively) (p < 0.05). Both patients and their significant others had comparable mean mental health composite scores (MCS) of 46.6 ± 10 and 46.4 ± 10, respectively (p > 0.05). CONCLUSION: Although significant others of persons with swallowing dysfunction have higher physical well-being than their partners, they exhibit the same reduction in mental well-being, which is significantly lower than the general population. The data suggest that clinicians should address the mental well-being of the partners of persons with severe swallowing dysfunction.

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.

Objective Fluoroscopic Outcomes After Endoscopic Staple Versus Laser Zenker's Diverticulotomy.

OBJECTIVE: Endoscopic Zenker's diverticulotomy (EZD) is typically performed via stapling (endoscopic staple diverticulotomy; ESD) or CO2 laser (endoscopic laser diverticulotomy; ELD). Conflicting reports exist on which approach provides optimal outcomes. This investigation compared objective fluoroscopic data between ESD and ELD. METHODS: A retrospective review of all patients undergoing primary EZD at a tertiary center between January 1, 2014 and January 10, 2022 was performed. Patients undergoing ESD and ELD were matched by preoperative diverticulum size. Primary outcome measures were postoperative diverticulum size and change in diverticulum size from pre- to postoperative swallowing fluoroscopy. Secondary outcome measures were the Eating Assessment Tool (EAT-10) score, penetration aspiration scale (PAS), pharyngeal constriction ratio (PCR), and pharyngoesophageal segment opening (PESo). RESULTS: Thirteen matched pairs with complete fluoroscopic data were identified. The mean (±SD) age of the cohort was 74.0 (±8.5) years. There were no age or gender differences between groups (p > 0.05). The mean pre-operative ZD size was 1.98 (±0.69) cm for ESD and 1.97 (±0.72) cm for ELD; the mean postoperative size was 0.84 (±0.62) cm for ESD and 0.34 (±0.27) cm for ELD (p < 0.05). Mean diverticulum size improved by 1.14 (±0.59) cm after ESD and 1.62 (±0.59) cm after ELD (p < 0.05). There were no significant differences in postoperative EAT-10, PAS, PCR, or PESo between groups. CONCLUSION: The data suggest that endoscopic laser Zenker's diverticulotomy results in a greater improvement in diverticulum size than endoscopic staple diverticulotomy. The data did not suggest a difference in postoperative dysphagia symptom scores or other objective fluoroscopic parameters between staple and laser diverticulotomy. LEVEL OF EVIDENCES: Level 3 Laryngoscope, 133:3057-3060, 2023.

Upper Instrumented Vertebrae, Number of Levels Fused, and Plate Morphology Do Not Affect Severity of Chronic Dysphagia After Anterior Cervical Spine Surgery.

BACKGROUND: Disordered swallowing, or dysphagia, is the most common complication after anterior cervical spine (ACS) surgery. Many operative factors are associated with development of dysphagia. The aim of this study was to explore how number of levels instrumented, specific levels fused, and plate morphology affect chronic dysphagia after ACS surgery. METHODS: Consecutive patients referred to a tertiary center for otolaryngology evaluation for chronic dysphagia after ACS surgery between 2012 and 2017 were enrolled. Basic demographic data were obtained. Plain radiographs were reviewed for number of levels fused, upper instrumented vertebrae, and plate morphology. Plate morphology was categorized as a closed, small window, large window, or no profile plate. The 10-item Eating Assessment Tool (EAT-10) was used to assess dysphagia severity. RESULTS: Of 171 patients referred for dysphagia, 126 met inclusion criteria; 54% were female, with a mean age of 63 years (range, 32-88 years). Mean EAT-10 score was 18.5 ± 10.1. Mean time from spine surgery to videofluoroscopic swallow study for dysphagia was 58.3 months. Mean number of levels fused was 2.2 ± 0.9. There were no significant differences in EAT-10 scores in single-level versus multilevel fusion (19.0 vs. 18.4, P = 0.76) as well as with regard to upper instrumented vertebrae or plate morphology. CONCLUSIONS: In this series of patients with chronic dysphagia following ACS surgery, the severity of dysphagia as measured by the EAT-10 was not affected by upper instrumented vertebrae, number of levels fused, or plate morphology.

Effect of Pretreatment Dysphagia on Postchemoradiation Swallowing Function in Head and Neck Cancer.

OBJECTIVES: Chemoradiation therapy (CRT) for head and neck cancer can have profound effects on swallowing function. Identification of risk factors for development of swallowing dysfunction after CRT may improve allocation of preventive strategies. The purpose of this study is to determine the association between pre-CRT dysphagia and post-CRT swallowing dysfunction. STUDY DESIGN: Retrospective cohort study. SETTING: Academic medical center. METHODS: Patients with head and neck cancer were evaluated before and 3 months after CRT. Dysphagia was assessed with the Eating Assessment Tool (EAT-10). Swallowing dysfunction was evaluated by a videofluoroscopic swallow study and the Penetration-Aspiration Scale and swallowing safety was evaluated by the Functional Oral Intake Scale. The association between pre-CRT EAT-10 scores and post-CRT swallowing dysfunction was evaluated. RESULTS: The mean ± SD post-CRT Functional Oral Intake Scale score was 6.5 ± 1.2 for individuals with a pre-CRT EAT-10 score <3 and 5.3 ± 1.9 for those with a pre-CRT EAT-10 score ≥3 (P < .001). The mean post-CRT Penetration-Aspiration Scale score was 2.2 ± 1.5 for individuals with a pre-CRT EAT-10 score <3 and 3.8 ± 2.6 for those with a pre-CRT EAT-10 score ≥3 (P < .001). After multivariate analysis adjusting for age, tumor subsite, T classification, and primary surgery, pre-CRT dysphagia (EAT-10 ≥3) was an independent predictor of post-CRT aspiration (odds ratio, 4.19 [95% CI, 1.08-16.20]; P = .04) and feeding tube dependence (odds ratio, 3.54 [95% CI, 1.01-12.33]; P = .04). CONCLUSION: The presence of dysphagia before chemoradiation for head and neck cancer is an independent predictor of swallowing dysfunction after completion of therapy. These results may help target intervention toward preventing swallowing dysfunction in high-risk individuals.

Autologous Muscle-Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer. STUDY DESIGN: Prospective, phase I, open label, clinical trial. METHODS: Oropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited. All patients had swallowing impairment but were not feeding tube dependent (Functional Oral Intake Scale [FOIS] ≥ 5). Muscle tissue (50-250 mg) was harvested from the vastus lateralis and 150 × 106 AMDCs were prepared (Cook MyoSite Inc., Pittsburgh, PA). The cells were injected into four sites throughout the intrinsic tongue musculature. Participants were followed for 24 months. The primary outcome measure was safety. Secondary endpoints included objective measures on swallowing fluoroscopy, oral and pharyngeal pressure, and changes in patient-reported outcomes. RESULTS: Ten individuals were enrolled. 100% (10/10) were male. The mean age of the cohort was 65 (±8.87) years. No serious adverse event occurred. Mean tongue pressure increased significantly from 26.3 (±11.1) to 31.8 (±9.5) kPa (P = .017). The mean penetration-aspiration scale did not significantly change from 5.6 (±2.1) to 6.8 (±1.8), and the mean FOIS did not significantly change from 5.4 (±0.5) to 4.6 (±0.7). The incidence of pneumonia was 30% (3/10) and only 10% (1/10) experienced deterioration in swallowing function throughout 2 years of follow-up. The mean eating assessment tool (EAT-10) did not significantly change from 24.1 (±5.57) to 21.3 (±6.3) (P = .12). CONCLUSION: Results of this phase I clinical trial demonstrate that injection of 150 × 106 AMDCs into the tongue is safe and may improve tongue strength, which is durable at 2 years. A blinded placebo-controlled trial is warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:523-527, 2022.

Predictors of Aspiration Pneumonia and Mortality in Patients with Dysphagia.

OBJECTIVES/HYPOTHESIS: To identify risk factors for pneumonia incidence in patients with dysphagia undergoing a videofluoroscopic swallow study (VFSS) in an outpatient tertiary-care center. STUDY DESIGN: Historical cohort study. METHODS: All individuals undergoing a VFSS between 10/02/13 and 07/30/15 were identified and followed historically for 2 years. Demographic information, medical history, and fluoroscopic data were collected. The 2-year incidence of pneumonia was obtained from the medical records and telephone interview. The incidence of pneumonia and death were calculated and risk factors for pneumonia and mortality were ascertained. RESULTS: 689 patients were followed for 2 years. The mean age (±standard deviation) of the cohort was 65 (±15.5) years. 49% (338/689) were female. The most common causes of dysphagia were cricopharyngeus muscle dysfunction (270/689), head and neck cancer (175/689), and neurodegenerative disease (56/689). The incidence of pneumonia was 22% (153/689). The incidence of death was 11%. Multivariable logistic regression revealed that chronic obstructive pulmonary disorder [COPD] (odds ratio [OR] = 2.36, 95% confidence interval [CI]: 1.33-4.19), hypertension (OR = 1.82, 95% CI: 1.23-2.73), tracheotomy status (OR = 2.96, 95% CI: 1.09-7.99), and vallecular residue (OR = 1.88, 95% CI: 1.24-2.85) were all significantly associated with an elevated risk of pneumonia. Kidney disease (OR = 1.27, 95% CI: 1.02-9.9), COPD (OR = 3.27, 95% CI: 1.65-6.49), vallecular residue (OR = 2.35, 95% CI: 1.35-4.1), male gender (OR = 2.21, 95% CI: 1.25-3.92), and low body mass index (OR: 1.12, 95% CI: 1.06-1.19) were independent adjusted risk factors for death. CONCLUSIONS: The incidence of aspiration pneumonia (22%) and death (11%) within 2-years of a VFSS was high. The greatest adjusted risk factors for incident pneumonia were tracheotomy (OR = 3.0), COPD (OR = 2.4) and vallecular residue (OR = 1.9). The greatest adjusted risk factors for death were COPD (OR = 3.3), vallecular residue (OR = 2.3), and male gender (OR = 2.2). LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1172-1176, 2022.

Endoscopic visualization for tracheoesophageal puncture tract sizing.

BACKGROUND: Accurate tracheoesophageal prosthesis (TEP) size is essential for optimal functioning. Current sizing techniques do not afford direct visualization. The clinical utility of direct visualization with unsedated transnasal esophagoscopy (TNE) to improve TEP sizing accuracy has not been established. AIMS/OBJECTIVES: The purpose of this investigation was to determine if endoscopic visualization with TNE during TEP fitting improves sizing accuracy. MATERIAL AND METHODS: Participants undergoing secondary TEP placement had their TEP sized without visualization and with visualization during TNE. The effect of endoscopic visualization on TEP sizing was assessed. RESULTS: The mean age (SD) of the cohort (N = 15) was 61.20 (±10.19) years. The percent disagreement between non-visualized and endoscopic-visualized puncture tract measurement was 60%. The mean difference in puncture tract length with visualization compared to without visualization was 1.75 mm (±1.91). Discordance between non-visualized and endoscopic-visualized puncture tract length was worse for persons with a history of radiation (66.7%) than without radiation (33.3%) (p < .05). The overall test agreement between endoscopic and non-endoscopic sizing techniques was moderate (Cohen's kappa coefficient = 0.254; (p < .05). CONCLUSION AND SIGNIFICANCE: The percent disagreement between non-visualized and endoscopic-visualized TEP sizing is high (60%). The data suggest that endoscopic visualization with TNE improves sizing accuracy during TEP placement.

Cervical Fibrosis as a Predictor of Dysphagia.

OBJECTIVE: Radiotherapy of head and neck cancer (HNCA) causes dysfunction through radiation-induced fibrosis (RIF). We hypothesize that the degree of cervical fibrosis is associated with swallowing dysfunction. This study evaluated the association between cervical fibrosis and swallowing dysfunction in patients after radiation therapy for HNCA. STUDY DESIGN: Cross sectional study. METHODOLOGY: A convenience sample of patients with dysphagia who were at least 1 year post radiation therapy for HNCA underwent simultaneous cervical ultrasound (US) and video-fluroscopic swallow study (VFSS). US determinants of fibrosis were measurements of sternocleidomastoid fascia (SCMF) thickness bilaterally at the level of the cricoid. Primary and secondary outcome variables on VFSS were pharyngeal constriction ratio, a validated measure of pharyngeal contractility, and penetration aspiration scale (PAS). A qualitative assessment of lateral neck rotation was performed as a functional measure of neck fibrosis. RESULTS: Simultaneous cervical US and VFSS examinations were performed on 18 patients with a history of radiotherapy for HNCA and on eight controls. The mean (±SD) age of the entire cohort (N = 26) was 66 (±10) years. Individuals with a history of radiation had significantly thinner mean SCMF (0.26 [±0.04 mm]) compared to controls (0.48 [±0.06 mm]; P < .05). Individuals with thinner SCMF were more likely to have moderate to severe restriction in lateral neck rotation, a higher PCR, and a higher PAS (P < .05). CONCLUSION: Thinner sternocleidomastoid fascia on ultrasound in patients having undergone radiotherapy for head and neck cancer was associated with reduced lateral neck movement, poorer pharyngeal constriction and greater penetration/aspiration scale. The data suggest that cervical fibrosis is associated with swallowing dysfunction in head and neck cancer survivors and support the notion that, "As the neck goes, so does the swallow." LEVEL OF EVIDENCE: 3. Laryngoscope, 131:548-552, 2021.

Inflammatory Effects of Thickened Water on the Lungs in a Murine Model of Recurrent Aspiration.

OBJECTIVE: Liquid thickeners are commonly recommended in individuals with dysphagia and recurrent aspiration as a strategy for pneumonia prevention. The goal of this study was to examine the effects of small amounts of aspirated liquid thickener on the lungs. STUDY DESIGN: Animal model. Prospective small animal clinical trial. METHODS: Adult Sprague Dawley rats (n = 19) were divided into two groups and underwent three intratracheal instillations of either xanthan gum-based nectar-thick water (0.1-0.25 mL/kg) or water-only control over the course of 8 days. Blood was collected from a peripheral vein on days 1 and 8 and submitted for complete blood count (CBC) analysis. Rats were euthanized 10 days after the last instillation, and the lungs were harvested. Histopathology was conducted on lung specimens by a blinded licensed veterinary pathologist and scored for evidence of lung injury and pneumonia. RESULTS: Fifteen animals (8 nectar-thickener group, 7 control group) survived until the endpoint of the study (day 18). Serum CBC did not show abnormalities at any timepoint in either group. Histological evidence of lung inflammation and edema were significantly greater in the nectar-thick group compared to controls (P < .05). Signs of inflammation included aggregates of foamy macrophages, expansion of bronchiolar lymphoid tissue, and large numbers of eosinophilic intraalveolar crystals. Histiocytic and neutrophilic pneumonia was noted in one animal that received thickened liquids. CONCLUSION: Recurrent aspiration of small amounts of thickened water resulted in significant pulmonary inflammation in a murine model of aspiration. Results of this study support the need for further investigation of liquid thickener safety and its efficacy in reducing the pulmonary complications of swallowing disorders. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1223-1228, 2021.

Fluoroscopic Swallowing Abnormalities in Dysphagic Patients Following Anterior Cervical Spine Surgery.

OBJECTIVES: To evaluate the precise objective fluoroscopic abnormalities in persons with dysphagia following anterior cervical spine surgery (ACSS). METHODS: 129 patients with dysphagia after ACSS were age and sex matched to 129 healthy controls. All individuals underwent videofluoroscopic swallow study (VFSS). VFSS parameters abstracted included upper esophageal sphincter (UES) opening, penetration aspiration scale (PAS), and pharyngeal constriction ratio (PCR). Other data collected included patient-reported outcome measures of voice and swallowing, number of levels fused, type of plate, vocal fold immobility, time from surgery to VFSS, and revision surgery status. RESULTS: The mean age of the entire cohort was 63 (SD ± 11) years. The mean number of levels fused was 2.2 (±0.9). 11.6% (15/129) were revision surgeries. The mean time from ACSS to VFSS was 58.3 months (±63.2). The majority of patients (72.9%) had anterior cervical discectomy and fusion (ACDF). For persons with dysphagia after ACSS, 7.8% (10/129) had endoscopic evidence of vocal fold immobility. The mean UES opening was 0.84 (±0.23) cm for patients after ACSS and 0.86 (±0.22) cm for controls (P > .0125). Mean PCR was 0.12 (±0.12) for persons after ACSS and 0.08 (±0.08) for controls, indicating significant post-surgical pharyngeal weakness (P < .0125). The median PAS was 1 (IQR 1) for persons after ACSS as well as for controls. For ACSS patients, PCR had a weak correlation with EAT-10 (P < .0125). CONCLUSION: Chronic swallowing dysfunction after ACSS appears to be secondary to pharyngeal weakness and not diminished UES opening, the presence of aspiration, vocal fold immobility, or ACSS instrumentation factors.Level of Evidence: 3b.

The relationship between posterior pharyngeal wall thickness and swallowing function after radiation therapy.

Background: Dysphagia is a complication following radiation therapy (RT) for head and neck cancers (HNC). Radiologic findings of posterior pharyngeal wall thickening (PPWT) after RT has not been quantified and correlated to swallowing outcomes.Aims/objective: To evaluate PPWT and its impact on swallowing function following RT.Material and methods: Retrospective analysis of pre- and three-month post-RT PPWT, demographics, oncologic history, and swallowing parameters of patients undergoing RT for HNC. Multivariate analysis of variance was performed to evaluate the effect of PPWT on swallowing outcomes.Results: The mean age of the cohort (n = 207) was 61.8 (± 11.29) years. The mean PPWT increased by 0.28 (± 0.19) cm (p = .00) three-months after RT. A significant difference in PPWT score between tumor subsites, χ2(2) = 45.883, p = .00, with the highest mean rank score of 135.97 for nasopharynx and 103.46 for oropharynx. PPWT was significantly associated with increased pyriform sinus retention, higher Penetration-Aspiration Scale (PAS) scores and post-deglutitive aspiration (p < .05).Conclusions and significance: PPWT increase significantly after RT for HNC. Increased PPWT was associated with mean radiation dose to the nasopharynx and oropharynx and was an independent risk factor for increased pharyngeal residue, higher PAS scores, and timing of aspiration (p < .05).

The effects of barium concentration levels on the pulmonary inflammatory response in a rat model of aspiration.

PURPOSE: Barium sulfate (Ba) suspension is the most widely used contrast agent for upper gastrointestinal and videofluoroscopic swallow studies (VFSS). The effect of Ba concentration on lung injury is uncertain. The aims of this study were to explore the effects of different barium concentrations on the respiratory organs and elucidate the underlying mechanisms of these effects in an established animal model of aspiration. METHODS: Animal model study. Eight-week-old male Sprague-Dawley rats were allocated into three groups (n = 12, each group). Two groups underwent tracheal instillation of low (30% w/v) and high (60% w/v) concentration Ba (low-Ba, high-Ba). A control group was instilled with saline. Half of the animals were euthanized on day 2 and the remaining half were euthanized on day 30. Histological and gene analyses were performed. RESULTS: Both low-Ba and high-Ba aspiration caused inflammatory cell infiltration in the lung at 2 days post aspiration with an increase in the expression of inflammatory cytokines. At 30 days post aspiration, small quantities of barium particles remained in the lung of the low-Ba group without any inflammatory reaction. Chronic inflammation was recognized in the high-Ba group up to 30 days post aspiration. CONCLUSION: A small amount of high concentration Ba (60% w/v) caused sustained inflammation in the rat lung at least 30 days after aspiration. Even with a small amount of low concentration Ba aspiration (30% w/v), Ba particles can remain in the lung over a month, causing sustained late effects.

Prevalence of profound laryngeal sensory neuropathy in head and neck cancer survivors with feeding tube-dependent oropharyngeal dysphagia.

BACKGROUND: Laryngopharyngeal sensory neuropathy (LSN) has been observed to be a contributing factor to swallowing dysfunction in head and neck cancer (HNC) survivors. METHODS: Retrospective review of 43 tube-dependent HNC survivors was conducted. LSN was assessed with direct palpation of the aryepiglottic fold and by traversing the true vocal folds without eliciting a cough reflex with a flexible laryngoscope. RESULTS: The primary tumor sites were oropharynx (51%), larynx (14%), nasopharynx (4.7%), oral cavity (14%), thyroid (4.7%), unknown primary (9.3%), and esophagus (2.3%). The prevalence of profound LSN was 79.1%. Objective fluoroscopic parameters contributing to swallowing dysfunction were diminished laryngohyoid elevation (100%), pharyngeal weakness (67%), and reduced lateral PES opening (37%). CONCLUSIONS: The prevalence of LSN in HNC survivors with feeding tube-dependent dysphagia is high (79.1%). The data suggest that LSN, in addition to fibrosis, pharyngoesophageal stenosis, and cranial nerve motor deficits contributes to swallowing dysfunction in these patients.

Esophageal A-ring is associated with the severity of gastroesophageal reflux.

BACKGROUND: The esophageal A-ring (EAR) is an anatomic finding appreciated on videofluoroscopic esophagram (VFE) at the junction of the tubular esophagus and esophageal vestibule. EARs are appreciated on a small subset (5%) of VFEs. We hypothesize that EARs represent a compensatory mechanism to protect against gastroesophageal reflux (GER). OBJECTIVE: To evaluate the association between EAR and GER. STUDY DESIGN: Case control study. METHODS: All persons having undergone ambulatory pH testing with an EAR identified on VFE between November 1, 2014 and June 30, 2014 were identified. All cases were matched to controls by age, gender, and the presence/absence of hiatal hernia. Subjective dysphagia severity was assessed with the EAT10 and the presence of erosive esophagitis and intestinal metaplasia on esophagoscopy was abstracted. RESULTS: The mean (±SD) age of the entire cohort (N = 20) was 63 (±7.7) years. 60% was female. The mean composite DeMeester pH score for persons with and without an EAR was 48.9 (±39.6) and 15.4 (±12.3), respectively (P = .033). The mean total % time of pH < 4 for persons with and without an EAR was 26.4 (±21.9) and 7.7 (±6.8), respectively (P = .034). The prevalence of erosive esophagitis among persons with and without an EAR was 70% and 10%, respectively (P = .019). CONCLUSION: There is a significant association between the presence of esophageal A-rings on esophagography and the severity of acid reflux on endoscopy and ambulatory pH testing. The data suggest that the presence of an esophageal A-ring may be either a compensatory mechanism to protect against gastroesophageal reflux and/or an inflammatory consequence of peptic esophagitis. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:951-954, 2020.

Swallowing Characteristics in Zenker's-like Diverticulum After Anterior Cervical Spine Surgery.

OBJECTIVES: A Zenker's diverticulum (ZD) is a hypopharyngeal pulsion diverticula caused by dysfunction of the cricopharyngeus muscle with herniation of hypopharyngeal mucosa through Killian's dehiscence. Anterior cervical spine surgery (ACSS) can cause a Zenker's-like traction diverticulum (ZTD) with a similar presentation but different pathophysiology. The purpose of this investigation was to compare the fluoroscopic parameters and surgical outcomes of ZTD after ACSS to those of typical ZD. STUDY DESIGN: Case-control study. METHODS: The charts of patients undergoing a videofluoroscopic swallow study after ACSS between January 1, 2014, and January 1, 2018, were evaluated for evidence of ZTD. Patients with ZTD were age and gender matched to persons with ZD. Fluoroscopic parameters and patient-reported outcomes were compared between groups. RESULTS: Eleven patients with ZTD were identified. The mean pharyngeal constriction ratio (PCR) was significantly higher for persons with ZTD (0.87 [±0.07] vs. 0.17 [±0.08]; P < 0.05). Mean hyolaryngeal elevation was significantly less (2.5 [±0.9] cm vs. 3.5 [±0.7] cm) and mean diverticulum size significantly smaller (1.3 [±1.0] cm vs. 2.3 [±2.0] cm) for persons with ZTD (P < 0.05). Five ZTD patients had exposed hardware necessitating open approach for removal. CONCLUSION: We report the largest cohort of ZTD after ACSS. ZTD are smaller than traditional Zenker's and associated with more pharyngeal weakness, poorer laryngeal elevation, and worse treatment outcomes. Although these diverticula can be managed endoscopically, the high percentage of exposed cervical hardware necessitates a thorough preoperative assessment and frequent need for open management and pharyngeal repair. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:1383-1387, 2020.

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

Validation of the PILL-5: A 5-Item Patient Reported Outcome Measure for Pill Dysphagia.

Objectives: Pill dysphagia is common and costly with a significant risk of pill retention, caustic injury, and poor medication compliance. The purpose of this investigation was to determine the validity and reliability of the PILL-5, a self-administered patient reported outcome measure (PROM) to quantify the degree of pill (tablet and capsule) dysphagia. The PILL-5 is a 5-item questionnaire with a maximum symptom score of 20. Methods: The PILL-5 was administered to 190 patients with dysphagia referred for videofluoroscopic esophagography (VFE). Construct validity was assessed by comparing PILL-5 composite scores to delayed barium tablet transit on VFE. Normative data was obtained by administering the instrument to a cohort of healthy community based volunteers. Internal consistency was assessed with the Cronbach alpha. Test/retest reliability was determined by administering the instrument to the same cohort of patients at two time points. Results: The mean PILL-5 was 5.6 (±4.9) for persons with dysphagia and 1.6 (±2.7) for healthy volunteers (p < 0.001). The internal consistency of the instrument was high (Cronbach alpha = 0.85). The mean PILL-5 was 4.3 (±4.1) for patients with normal transit and 7.6 (±5.3) for patients with delayed barium tablet transit on esophagography, indicating excellent criterion based validity (p < 0.001). Reproducibility was high with an intraclass correlation coefficient of 0.83 (p < 0.001). Conclusions: Healthy individuals report some degree of swallowing difficulty with pills. Normative data suggest that a PILL-5 > 6 is abnormal (mean + 2 SD). The instrument demonstrated excellent criterion based validity and reliability. The PILL-5 is the first validated patient reported outcome measure for pill dysphagia.

The Prevalence of Cricopharyngeal Webs in Elderly Cadavers.

OBJECTIVE: Cricopharyngeal webs (CPW) are a frequent cause of solid food dysphagia. They are difficult to diagnose and are often missed on swallowing fluoroscopy. The prevalence of CPWs is uncertain. The purpose of this study was to determine the prevalence of CPWs in elderly cadavers. METHODS: Direct laryngoscopy and cervical esophagoscopy were performed in 19 embalmed cadavers by independent two-clinician consensus. Cadaver demographics and the presence and laterality of a CPW were recorded. The prevalence of CPW was calculated, and the size of the cricopharyngeus muscle (CPM) was quantified. RESULTS: The mean age of the cohort was 83 ( ± 12) years. Fifty-three percent were female, and the mean body mass index was 19.7 ( ± 3). The causes of death were cardiovascular disease (10 of 19), cancer (5 of 19), and respiratory failure (4 of 19). A CPW was present in 68% (13 of 19) of cadavers. Forty-seven percent (9 of 19) had a unilateral web, and 21% (4 of 19) had a bilateral web. There was no laterality predominance (P > 0.05). Forty-two percent (8 of 19) had no CPM prominence; 32% (6 of 19) had a small/moderate CPM prominence; and 26% (5 of 19) had a significant CPM prominence. CONCLUSION: The prevalence of cricopharyngeal webs in elderly cadavers is high (68%). The clinician should maintain a high index of suspicion for CPWs in patients with no other identifiable etiology of solid food dysphagia. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:63-66, 2019.