Lott, David G

ABSTRACT Objective To estimate the pooled prevalence of lymphedema among adults with mucosal head and neck cancer treated with radiation therapy. Data Sources PubMed, Embase, Scopus, and Cochrane Library. Review Methods A comprehensive literature search of PubMed, Embase, Scopus, and Cochrane Library (2000–2025) identified cohort, case series, cross‐sectional, and clinical trial studies reporting lymphedema after radiotherapy for head and neck cancer. Logit‐transformed lymphedema prevalence was pooled using a DerSimonian‐Laird random‐effects model with Hartung‐Knapp‐Sidik‐Jonkman variance correction; statistical heterogeneity was evaluated using I 2 . This review was not prospectively registered. Results A total of 26 studies ( n = 3133 patients) met inclusion criteria. The pooled prevalence of lymphedema was 49% (95% CI, 36%–62%), with considerable heterogeneity (I 2 = 94%). Subgroup analyses yielded a pooled prevalence of 37% (12%–71%) for external and 45% (31%–60%) for internal lymphedema. Among studies reporting severity‐graded data, the pooled prevalence of clinically significant (grade ≥ 2) lymphedema was 32% (14%–59%). Lymphedema definitions and assessment methods varied across the included studies, most commonly employing clinical grading. Methodological quality was mixed, reflecting the predominantly retrospective, single‐arm nature of the available evidence. Overall certainty of evidence was very low. Funnel plot inspection and Egger's test suggested small‐study effects ( p = 0.06). Conclusion Lymphedema affects nearly half of patients following radiation for head and neck cancer. These findings may support routine surveillance, early identification, and timely referral for lymphedema management within survivorship care pathways. Future prospective studies should adopt standardized definitions and outcome measures to refine risk estimates and guide prevention strategies. Level of Evidence N/A.

ABSTRACT Objective To compare antigen removal processing with conventional sodium dodecyl sulfate decellularization for generating laryngotracheoesophageal scaffolds, focusing on preservation of extracellular matrix integrity and removal of immunogenic material. Methods Laryngotracheoesophageal complexes were harvested from C57BL/6 mice and processed using either antigen removal or sodium dodecyl sulfate‐based protocols. Scaffolds were analyzed for residual double‐stranded DNA content, collagen preservation, glycosaminoglycan retention, and ultrastructural integrity via histology, quantitative image analysis, and scanning electron microscopy. Results Both antigen removal and sodium dodecyl sulfate protocols achieved effective decellularization, with comparable dsDNA removal relative to native controls ( p = 0.001; p < 0.001). Antigen removal scaffolds demonstrated better collagen preservation compared to sodium dodecyl scaffolds, which exhibited marked collagen depletion (Muscle: Collagen I, p < 0.001; Collagen III, p < 0.01; Cartilage: Collagen I, p < 0.05; Collagen III, p < 0.01). Both antigen removal and sodium dodecyl sulfate groups showed significant glycosaminoglycan depletion compared with controls ( p < 0.001). Scanning electron microscopy confirmed superior ultrastructural preservation in antigen removal‐treated scaffolds, characterized by intact fibrillar architecture and lacunar morphology, while sodium dodecyl sulfate scaffolds demonstrated collapsed lacunae and irregular extracellular matrix organization. Conclusion Antigen removal processing generates laryngotracheoesophageal scaffolds with enhanced extracellular matrix preservation compared with conventional sodium dodecyl sulfate decellularization, while maintaining equivalent levels of antigen elimination. Retention of collagen and ultrastructure suggests antigen removal scaffolds may provide superior biomechanical and biologic performance for laryngeal tissue engineering. Although glycosaminoglycan depletion remains a limitation in both approaches, antigen removal scaffolds represent a promising pathway toward clinically translatable alternatives to immunosuppression‐dependent laryngotracheoesophageal repair. Level of Evidence Preclinical.

ABSTRACT Objectives Laryngeal chondrosarcoma (LC) is a rare tumor accounting for less than 1% of all laryngeal cancers. While surgery is the primary treatment, national trends in management and outcomes remain poorly defined. This study aimed to analyze incidence, survival, and treatment strategies for LC using the Surveillance, Epidemiology, and End Results (SEER) database. Methods Patients with LC diagnosed between 2000 and 2021 were identified from SEER. Demographic, treatment, and survival data were analyzed. Kaplan–Meier analysis and multivariate Cox regression were used to analyze survival outcomes. Results In total, 351 patients with LC were identified, representing 0.3% of all laryngeal malignancies. Among patients with treatment data, 53.3% underwent local excision or partial laryngectomy, 27.5% underwent total laryngectomy (TL), and 19.2% received no surgery. Ten‐year disease‐specific survival was 84.8%. Patients undergoing partial resection demonstrated significantly improved survival compared with TL ( p < 0.05), although this finding is likely confounded by tumor size and stage. On multivariate analysis, advanced stage (HR 2.59, 95% CI 1.68–3.97), older age (HR 1.66, 95% CI 1.36–1.99), and TL (HR 2.95, 95% CI 1.88–4.62) were associated with worse survival. Conclusion LC remains rare but carries favorable long‐term survival. National trends demonstrate a shift toward organ‐preserving surgery, with partial resections increasingly favored over TL. Prognosis is most strongly influenced by age and stage, while radiation therapy appears to play a little role. These findings support organ preservation in appropriately selected patients and highlight the need for prospective studies integrating oncologic and functional outcomes. Level of Evidence 4

ABSTRACT Objective With regulatory approval of HPV‐specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. Data Sources and Methods RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. Results Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case‐by‐case basis. HPV ‐specific immunotherapy that induces an HPV ‐specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first‐line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second‐line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally‐administered adjuvant should be considered. Conclusion This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options. Level of Evidence 5

ABSTRACT Objective To evaluate the long‐term safety and clinical effect of INO‐3107 immunotherapy in adults with recurrent respiratory papillomatosis (RRP). Methods RRP‐002 was a retrospective, observational extension study that followed patients enrolled in the 52‐week RRP‐001 study. Patients with moderate to severe juvenile or adult‐onset RRP who had undergone ≥ 2 surgical interventions in the year preceding dosing were eligible for enrollment in RRP‐001. Participants underwent surgical debulking within 14 days prior to initial dosing and then received INO‐3107 on Day 0, Weeks 3, 6, and 9. Efficacy assessments during RRP‐002 follow‐up were the frequency of surgical interventions and alternative medication use. The safety evaluation included reported serious adverse events (SAEs). Results Twenty‐eight (28) of 32 participants from the 52‐week RRP‐001 study were enrolled in RRP‐002. The median follow‐up time for RRP‐002 was 1.8 years (range: 1.2–2.4 years) for a total median assessment time of 2.8 years (range: 1.0–3.5 years). There were no SAEs or long‐term safety concerns identified. The mean number of surgeries was reduced from 4.1 in the pre‐treatment period to 1.7 in the first year post‐INO‐3107 treatment (Year 1) to 0.9 in the second year (Year 2). The complete response rate (0 surgeries per year) increased from 28% (9/32) in Year 1 to 50% (14/28) in Year 2. Conclusion INO‐3107 is well tolerated and provides a continued clinical effect against HPV‐6 and 11 RRP that results in further reduction of the surgical burden observed in Year 1. These data support the role of INO‐3107 immunotherapy for adult patients with RRP. Level of Evidence: III.

Abstract Objective Determine relationship between frailty and hospital mortality, length of stay, cost, and medical and surgical complications in Zenker diverticulum surgery. Study Design Retrospective cross‐sectional. Setting National database. Methods Data from the National Inpatient Sample for 712 patients who underwent surgery for Zenker diverticulum 2016 to 2021 were analyzed using multivariate regressions. Frailty was defined as at least 1 frailty‐defining diagnosis from the Johns Hopkins ACG® Frailty Indicator. Elixhauser Comorbidity Index was calculated to quantify comorbidity burden. Results 12.2% of patients were identified as frail, 77.0% of whom had a weight loss or malnutrition diagnosis. Frailty predicted increased length of stay (mean, 4.09 days [95% CI: 2.98‐5.20]) and increased costs (mean, $10,500.36 [95% CI: $6885.76‐$14,114.95]). Frail patients were more likely to have medical complications compared to non‐frail patients (OR = 2.84 [95% CI: 1.66‐4.84]). Elixhauser Comorbidity Index was predictive of hospital mortality (OR = 1.78 [95% CI: 1.27‐2.51]) and likelihood of endoscopic surgical complications (OR = 1.25 [95% CI: 1.05‐1.47]), but frailty was not predictive of either. Conclusion Frailty is not associated with increased risk of surgical complications or mortality and is not an absolute contraindication to Zenker diverticulum surgery. Frailty predicts length of stay, costs, and medical complications in Zenker diverticulum surgery and should be used with comorbidity to stratify patient risk for surgery. Prospective studies involving frail patients could help develop a standardized method for assessing surgical fitness, potentially expanding treatment options and improving outcomes for this population. Level of Evidence 2.

Comparative analysis of fibrin sealant and recombinant thrombin hydrogels reveals distinct microarchitectures and cellular responses, emphasizing recombinant thrombin’s potential to enhance cellular activity and enable vesicle delivery.

Objectives/Hypothesis: Botulinum neurotoxin type-A (BoNT-A) injection into the true vocal cords is an effective treatment for restoring vocal functionality in adductor spasmodic dysphonia (AdSD). The Glasgow Benefit Inventory was developed to measure quality of life change following any otolaryngologic intervention and was recently revised to a 5-factor subdomain (GBI-5F) questionnaire to improve clinical utility. The study aim was to utilize the GBI-5F to measure patient-reported quality of life change in AdSD patients following BoNT-A injection. Methods: The GBI-5F questionnaire was administered to patients diagnosed with AdSD who received a BoNT-A vocal cord injection between December 2022 and May 2023. All patients had received multiple prior injections. GBI-5F subdomains and demographics were analyzed to identify areas for patient-reported improvement. Results: Sixty-six patients completed the GBI-5F. There were 52 (78.7%) females and average age was 69.4 years. The median total benefit score was +40.0 (interquartile range [IQR], 20.0). Median subdomain scores were +83.3 (IQR, 50.0) for quality of life, +50.0 (IQR, 50.0) for self-confidence, +33.3 (IQR, 33.3) for social involvement, +16.7 (IQR, 50.0) for support, and 0.0 (IQR, 16.7) for general health. Differences in the individual subdomain scores were statistically significant ( P < .0001). No significant differences were found in the total GBI-5F score or any subdomain according to sex or presence of vocal tremor (all P > .05). A moderately positive correlation was noted between median total score and percent functional improvement (r = 0.46, P < .001). Conclusion: Botulinum injection therapy for AdSD provides overall benefit to patients as measured by the GBI-5F, with particular improvement observed for perceived quality of life, self-confidence, and social involvement. Sex, presence/absence of vocal tremor, and age do not appear to modify benefit, though degree of functional improvement is positively correlated with total score.

Objective: Recurrent respiratory papillomatosis (RRP) is a rare disease of the airway for which there is no known cure. Treatment involves the surgical removal or destruction of these lesions. There has been a long-standing debate over the effectiveness of the adjuvant intralesional injection of the immune modifying agent bevacizumab. This study is a systematic review investigating the effect of adjuvant intralesional bevacizumab on patients with laryngeal papillomatosis. The main objective was to assess functional outcomes and efficacy. Data Sources: Pubmed, Google Scholar, and Web of Science. Review Methods: Search words were “intralesional bevacizumab” AND “recurrent respiratory papillomatosis.” Sources were systematically identified using inclusion and exclusion criteria (ie, study publication must post-date 2000, must be peer-reviewed, investigate patients with RRP, apply bevacizumab intralesionally, not systemically). Findings were then collected and analyzed. Results: Ten studies were included for analysis. The majority of these studies found an increase in the surgical interval, voice outcomes, and a decrease in tumor burden in most patients. No studies reported side effects or lasting complications related to the bevacizumab injection. Conclusion: This systematic review provides further evidence for the safety of intralesional bevacizumab injections and their likely positive effect on disease control. Future research would benefit from the implementation of standardized documentation of RRP outcomes.