Palatal Coupling Maneuvers Do Not Predict Hypoglossal Nerve Stimulator Treatment Efficacy.

OBJECTIVE(S): Maneuvers during drug-induced sleep endoscopy (DISE), for patients with obstructive sleep apnea (OSA), have been used as predictors for success with oral appliances. Hypoglossal nerve stimulation (HGNS) promotes opening at the velum through palatoglossus coupling. In this study, we evaluate maneuvers during DISE as predictors for HGNS treatment efficacy. METHODS: We evaluated patients undergoing HGNS between November, 2014 and February, 2021. We assessed maneuvers including jaw thrust and chin lift during preoperative DISE. The impact of tongue base and palatal opening during these maneuvers were rated from 1 to 4 (1: no improvement, 2: mild improvement, 3: moderate improvement, 4: significant improvement). Patients were grouped by a score of 1-2 (weak response) or 3-4 (strong response). Apnea hypopnea index (AHI) change was calculated from the difference between preoperative and postoperative sleep study. RESULTS: One hundred and seventy one patients were included. With jaw thrust, there was no significant difference in AHI change between patients with weak or strong response at the palate (n = 68 vs. 94, 9.5 vs. 13.6, p = 0.21) or tongue base (n = 24 vs. 138, 16.6 vs. 11.3, p = 0.24). On chin lift, there was no significant difference at the palate (n = 82 vs. 18, 13.9 vs. 11.4, p = 0.63) or tongue base (n = 92 vs. 72, 10.8 vs. 14.6, p = 0.24). On multiple linear regression analysis, lower body mass index, higher preoperative AHI, and higher preoperative oxygen nadir were associated with a larger AHI change. CONCLUSION: Palatal coupling maneuvers during DISE are not predictive of AHI change with HGNS. Findings using these maneuvers should not preclude HGNS candidacy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:431-436, 2023.

Synthetic Triterpenoid RTA-408: Limits Radiation Damage to Normal Tissue.

OBJECTIVES/HYPOTHESIS: To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model. STUDY DESIGN: Randomized, prospective study using an in vivo rat model. METHODS: Experimental animal study utilizing Sprague-Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA-408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points. RESULTS: The first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16-45) in the radiation control group, 3% (95% CI 0-11) in the nonirradiated control, and 3% (95% CI 0.2-10) in the radiation group treated with RTA-408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis. CONCLUSIONS: Administration of RTA-408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery. LEVEL OF EVIDENCE: Foundational Evidence, Animal Research Laryngoscope, 132:1196-1204, 2022.

Opioid Usage and Pain Control in Benign Oropharyngeal Surgery: An Observational Prospective Study.

OBJECTIVES: Little data is available on opioid usage in the adult population for benign oropharyngeal surgery. The objective here is to evaluate opioid prescribing patterns, opioid consumption, and patient pain patterns following benign oropharyngeal surgery, specifically tonsillectomy and adenoidectomy, tonsillectomy alone, and expansion sphincter pharyngoplasty. METHODS: Patients aged ≥18 years old and received a tonsillectomy, tonsillectomy and adenoidectomy, or expansion sphincter pharyngoplasty between November 2019 and August 2020 were included. Patients were provided a survey which included a visual analog scale for recording their pain postoperatively and the amount of opioid they had remaining. RESULTS: About 103 patients completed the post-operative questionnaire. Patients were prescribed 38 837 morphine milligram equivalents and used 28 644: approximately 26% went unused, which is the equivalent of 1346 5 mg oxycodone pills. Opioid consumption correlated with the initial dosage: patients consumed 12% more narcotic on average as the initial prescription went upwards by 50 morphine milligram equivalents. Obstructive sleep apnea, history of smoking, and being female predicted increased opioid usage in this cohort. Pain was reported the highest on postoperative day 1. A prescription of approximately 225 morphine milligram equivalents (150 mg oxycodone) was associated with decreased opioid use in this cohort. Larger initial prescriptions did not result in fewer requests for refills. CONCLUSION: A significant amount of opioid medication went unused in this study. A prescription of 225 morphine milligram equivalents (or 150 mg oxycodone) provided appropriate analgesia for the majority of patients. Larger prescriptions may result in increased opioid consumption and may not reduce the amount of refills. More study is needed to confirm these findings.

Evaluating the impact of smoking on disease-specific survival outcomes in patients with human papillomavirus-associated oropharyngeal cancer treated with transoral robotic surgery.

BACKGROUND: When treated nonsurgically with definitive chemoradiation, smokers with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a worse prognosis compared with their nonsmoking counterparts. To the authors' knowledge, the prognostic significance of smoking in surgically treated patients is unknown. METHODS: The current study is a retrospective case series of patients with HPV-positive OPSCC who underwent upfront transoral robotic surgery at a single institution from 2010 through 2017. Exclusion criteria were nonoropharyngeal primary tumors, histology other than SCC, HPV-negative tumors, previous history of head and neck cancer, and/or previous head and neck radiotherapy. Recurrence-free survival (RFS), overall survival, and disease-specific survival were compared using the Kaplan-Meier method and the log-rank test. Smoking history was categorized as never smokers (<1 pack-year), current smokers (smoking at the time of the cancer diagnosis), and former smokers. RESULTS: A total of 258 patients met the study criteria. The average age was 60 years, and approximately 87% of patients were male. A total of 148 patients (57.4%) were smokers whereas 110 (42.6%) reported never smoking. There were 44 active smokers (17.1%) and 104 former smokers (40.3%). The median follow-up was 3.23 years. There were 17 patients of disease recurrence. Smoking pack-year history was not found to be significant for RFS (hazard ratio, 1.01; 95% CI, 0.99-1.03 [P = .45]). There was no significant difference in RFS noted between never and ever smokers (92% vs 89.8%; P = .85) nor was there a difference observed between never, former, and current smokers (92% vs 91.5% vs 86.1%, respectively; P = .69). CONCLUSIONS: A smoking history is common in patients with HPV-positive OPSCC. In the current study, HPV-positive smokers were found to have excellent survival and locoregional control, similar to their nonsmoking counterparts. The results of the current study do not support the exclusion of smokers with early-stage, HPV-positive OPSCC from transoral robotic surgery-based deintensification trials.

AJCC-8ed nodal staging does not predict outcomes in surgically managed HPV-associated oropharyngeal cancer.

OBJECTIVE: To assess the pathological outcomes of surgically-managed human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) using the 8th Edition of the American Joint Committee on Cancer Staging Manual (AJCC-8ed). MATERIALS AND METHODS: A retrospective review was conducted of 156 patients with previously untreated OPSCC who underwent primary TORS between March 2010 and February 2015 to evaluate the impact of the new AJCC-8ed pathologic staging system. Only patients who had complete pathologic staging with neck dissection and at least 2 years of follow-up records or disease recurrence within 2 years were included for analysis. RESULTS AND CONCLUSIONS: Of the 156 patients, 116 patients had neck dissections and adequate follow-up data. There were 10 total recurrences, including 2 regional recurrences and 1 local recurrence. Lymph node size, number of positive lymph nodes, and presence of any positive nodes were not associated with recurrence for HPV-positive patients. The presence of extranodal extension approached significance. Pathologic N-stage was not predictive of recurrence under the AJCC-7ed or the AJCC-8ed systems. Cancer staging under the AJCC-8ed, but not the AJCC-7ed system was significantly associated with recurrence. In conclusion, pathologic node status as defined in the AJCC-8ed pathologic staging system does not appear to drive prognosis for surgically managed patients. While the new AJCC-8ed staging is an improvement in prognostication, the use of T-stage alone is still a better predictor of recurrence. TORS with adjuvant therapy determined by pathologic findings provides excellent locoregional control for HPV-positive OPSCC.

Positron emission tomography/computed tomography after primary transoral robotic surgery for oropharyngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To assess the first post-treatment positron emission tomography/computed tomography (PET/CT) in prediction of disease-free survival after primary transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) with or without adjuvant chemoradiation. STUDY DESIGN: Retrospective review. METHODS: Ninety-five patients with OPSCC treated with primary TORS from 2010 to 2014 at a single tertiary academic center were evaluated with PET/CT. Imaging was performed between 2 and 7 months after completing all treatment. Radiology findings were categorized as 1) negative, noting either complete resolution of foci without evidence of disease or anatomical changes likely attributed to treatment; 2) equivocal, noting equal likelihood of malignancy versus treatment-related changes; or 3) positive, noting either findings concerning for malignancy or new hyperactivity not attributed to treatment-related changes. The median follow-up time was 31 months (range, 23-63 months). Recurrence was defined as biopsy-proven invasive malignancy or clinical suspicion sufficient to initiate treatment occurring within 3 years of the completion of all treatment. RESULTS: Of 95 total patients with at least 2 years of follow-up records, 26 had positive post-treatment PET/CT results, with five experiencing actual recurrences. Of 69 patients with negative post-treatment PET/CT results, none experienced recurrences. These results indicate a sensitivity of 100%, specificity of 77%, positive predictive value of 19%, and negative predictive value of 100%. CONCLUSIONS: A majority of TORS patients (73%) will have a negative first post-treatment PET/CT. A single negative post-treatment PET/CT is strongly correlated with 2-year disease-free survival in patients treated with primary TORS and may warrant decreased surveillance imaging. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:2050-2056, 2017.

Biochemical Effects of Exercise on a Fasciocutaneous Flap in a Rat Model.

IMPORTANCE: An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear. OBJECTIVE: To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model. DESIGN, SETTING, AND PARTICIPANTS: Eighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013). A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from the proximal, middle, and distal portions on postoperative days 0, 2, 5, and 9. Flap survival was analyzed planimetrically, and biopsy specimens were analyzed by hematoxylin-eosin-stained microscopy and immunoblotting. The housing, exercise, surgery, and analysis of the rats were conducted at a single basic science research laboratory at the tertiary care center campus of Thomas Jefferson University in Philadelphia, Pennsylvania. EXPOSURES: The rats were caged for 14 days or housed in a cage connected to an exercise wheel and pedometer. MAIN OUTCOMES AND MEASURES: Study measures were gross and micrographic necrosis and expression of proteins within cell survival and apoptosis pathways. RESULTS: A total of 18 rats were studied, 9 in the RAG and 9 in the EAG. the mean (SEM) amount of necrosis in flaps was 41.3% (3%) in the RAG rats and 10.5% (3.5%) in the EAG rats (P < .001). Immunoblotting revealed increased Caspase-9 activity resulting in poly-(adenosine diphosphate-ribose) polymerase 1 cleavage in the RAG vs the EAG, as well as lower phosphorylated protein kinase B (also known as Akt), signal transducer and activator of transcription 3, and total B-cell leukemia/lymphoma 2 protein levels. Throughout the postoperative period, the cumulative vascular endothelial growth factor A levels of the EAG flaps were significantly higher than those of the RAG flaps (2.30 vs 1.25 fold induction [FI], P = .002), with differences of 2.76 vs 1.54 FI in the proximal segment, 2.40 vs 1.20 FI in the middle segment, and 1.90 vs 0.79 FI in the distal segment. A similar response was noted when comparing phosphorylated Akt, with cumulative mean (SEM) p-Akt expression levels of 0.62 (0.04) for RAG and 1.98 (0.09) for EAG (P = .002 between the 2 groups). CONCLUSIONS AND RELEVANCE: Voluntary preoperative exercise improves survival in pedicled fasciocutaneous flaps; the EAG rats had less necrosis, decreased apoptotic markers, and increased amounts of vascular endothelial growth factor A and prosurvival proteins. These results have implications to increase flap survival in other mammal populations, such as humans. LEVEL OF EVIDENCE: 3.