Evaluating human papillomavirus testing, prevalence, and association with prognosis in head and neck squamous cell carcinoma by subsite: A national cancer database study.

PURPOSE: To compare human papillomavirus (HPV) testing, prevalence, and association with prognosis between head and neck squamous cell carcinoma (HNSCC) subsites. MATERIALS AND METHODS: This study utilized the National Cancer Database (NCDB) to identify patients diagnosed with HNSCC between 2010 and 2017. Rates of HPV testing, HPV-positivity, and changes in these rates over time were measured by subsite. The impact of HPV-positivity on overall survival across six head and neck subsites was assessed using multivariable-adjusted Cox proportional hazards analysis. RESULTS: A total of 121,550 patients were included. Of this cohort, 87,575 (72.1%) were tested for HPV, with the oropharynx (55,049/64,158; 85.8%) displaying the highest rates of testing and the sinonasal tract (1519/2853; 53.2%) displaying the lowest testing rates. Of the 86,136 with a definitive result, 46,878 (54.4%) were HPV-positive, with the oropharynx (40,313/54,205; 74.4%) displaying the highest rates of HPV-positivity and the oral cavity (1818/11,505; 15.8%) displaying the lowest. HPV-positive malignancy was associated with significantly improved adjusted overall survival in the oropharynx (HR = 0.42 [95% CI: 0.43-0.47]), oral cavity (HR = 0.86 [95% CI: 0.79-0.95]), sinonasal tract (HR = 0.63 [95% CI: 0.48-0.83]), larynx (HR = 0.78 [95% CI: 0.71-0.87]), and hypopharynx (HR = 0.56 [95% CI: 0.48-0.66]), but not the nasopharynx (HR = 0.93 [95% CI: 0.77-1.14]). CONCLUSION: HPV testing rates were significantly lower in non-oropharyngeal subsites. This is relevant as HPV-associated disease displayed significantly improved overall survival in both the oropharynx and four of five non-oropharyngeal subsites. While validation with prospective studies is necessary, these findings may warrant HPV testing in all HNSCC subsites.

Early feeding after free flap reconstruction of the oral cavity: A systematic review and meta-analysis.

BACKGROUND: Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6-14 days post-operatively due to concern for orocutaneous fistula development. METHODS: Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed- and random-effects meta-analyses were used. RESULTS: One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = -0.02, p = 0.06) or free flap failure (RD = -0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference [days] = -2.43, p < 0.01). CONCLUSIONS: While further prospective trials are necessary, initiation of oral intake before post-operative day 5 may be appropriate in properly selected patients following oral reconstruction.

Circulating Tumor HPV DNA in Patients With Head and Neck Carcinoma: Correlation With HPV Genotyping.

Circulating tumor human papillomavirus DNA (ctHPVDNA) testing using digital-droplet polymerase chain reaction (PCR) detects fragments of tumor-modified human papillomavirus (HPV) in the plasma of patients with HPV-associated head and neck squamous cell carcinomas (HNSCCs). Its impact on tumor surveillance and primary diagnosis is limited by unresolved issues relating to sensitivity and specificity. The study population consisted of patients with HNSCC who had undergone ctHPVDNA testing. HPV status was determined by p16 immunohistochemistry and PCR-HPV genotyping on the tumor samples. For discrepant cases (HPV-positive/ctHPVDNA-negative), HPV status was confirmed by RNA in situ hybridization and, when possible, targeted single-nucleotide polymorphisms genotyping. A total of 167 patients had ctHPVDNA testing, and 141 tumors were HPV positive by p16 immunohistochemistry and PCR genotyping. Genotypes included types 16 (91.5%), 33 (4.3%), 35 (2.1%), and 18 (2.1%). ctHPVDNA was detected in 133 (94.3%) of HPV-positive HNSCCs but in none of the HPV-negative HNSCCs. Four of the 5 p16-positive cases that were negative by PCR and ctHPVDNA were positive by RNA in situ hybridization, and in 2 of these cases, rare high-risk genotypes were identified. ctHPVDNA had a sensitivity of 91.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 63.6%. The likelihood that patients with HPV-positive HNSCC have detectable ctHPVDNA is high. Non-HPV16 genotypes contribute to discrepancies but only in a small subset of cases. This finding validates ongoing efforts to use ctHPVDNA as a surveillance tool, and even as a primary diagnostic assay in patients presenting with masses in the neck and/or oropharynx.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer.

Importance: There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. Objective: To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. Design, Setting, and Participants: This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Main Outcomes and Measures: Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Results: Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. Conclusions and Relevance: This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Neutrophil-to-lymphocyte ratio as a predictor of surgical outcomes in head and neck cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation that is associated with adverse oncologic and surgical outcomes. We investigated the use of NLR as a prognostic indicator of complications of head and neck cancer (HNC) surgeries. METHODS: We conducted a retrospective study of 11 187 Veterans who underwent HNC surgery between 2000 and 2020. We calculated preoperative NLR values and fit logistic regression models adjusting for potential confounding factors, comparing high-NLR patients to low-NLR patients. RESULTS: The cohort had a median age of 63 and was 98% men. High-NLR patients had increased odds of 30-day mortality (p < 0.001), having 1+ perioperative complications (p < 0.001), sepsis (p = 0.03), failure to wean from mechanical ventilation (p = 0.04), pneumonia (p < 0.001), and pulmonary embolism (p = 0.02) compared with low-NLR patients. CONCLUSION: NLR was a robust, independent predictor of 30-day mortality, having 1+ surgical complications, sepsis, failure to wean from mechanical ventilation, pneumonia, and pulmonary embolism.

Prophylactic feeding tube placement for squamous cell carcinoma of the head and neck.

BACKGROUND: Percutaneous endoscopic gastronomy (PEG) tubes are commonly used to administer enteral nutrition during head and neck cancer (HNC) treatment. However, the benefits of placing a prophylactic feeding tube (PFT; prior to radiotherapy [RT]) or reactive feeding tube (RFT, after RT initiation) are unclear. We sought to compare survival, body mass trends, and hospitalization rates between strategies. METHODS: We conducted a retrospective cohort study of 11,473 Veterans with stages III-IVC HNC treated with chemoradiotherapy. Patients with PEG tube placement within 30 days prior to treatment initiation (PFT) were compared to all other patients (non-PFT) or patients with PEG tube placement within 3 months after treatment initiation placement (RFT). We compared survival, longitudinal body mass changes, and hospitalization rates for PFT versus non-PFT or RFT patients in propensity score (PS)-matched Cox regression models. RESULTS: 3,186 (28 %) patients received PFT and 8,287 (72 %) were non-PFT, of which 1,874 (23 %) received RFT. After PS-matching, there were no significant differences in overall survival (HR 0.97, 95 % CI 0.92-1.02), HNC-specific survival (HR 0.98, 95 % CI 0.92-1.09), change in BMI (p = 0.24), or hospitalization rates between PFT and non-PFT groups. Significant differences in hospitalization rates between PFT and RFT groups persisted after PS-matching (-0.11 hospitalizations/month), but no differences were found for other outcomes. CONCLUSION: Timing of PEG tube placement in Veterans with HNC was not associated with any significant survival or body mass advantage. However, patients who received PFT had a lower hospitalization rate than those who received RFT.

The Sinai Robotic Surgery Trial in HPV-related oropharyngeal squamous cell carcinoma (SIRS 2.0 trial) - study protocol for a phase II non-randomized non-inferiority trial.

Background: Human papillomavirus associated oropharyngeal squamous cell carcinoma (HPVOPSCC) usually affects a younger patient population. As such, the risk for long term toxicity associated with therapy is an important consideration. Multiple trials focused on de-escalation of therapy to preserve survival outcomes while minimizing treatment toxicity are currently in progress, however the question of which patients are ideal candidates for de-escalation remains unanswered. Circulating tumor DNA (cfHPVDNA) has emerged as a means of monitoring disease in patients with HPVOPSCC. Undetectable postoperative cfHPVDNA levels portend a better prognosis and by extension, may identify ideal candidates for de-escalation therapy. We propose an overview and rationale for a new institutional clinical trial protocol focusing on the use of cfHPVDNA to risk stratify patients for adjuvant therapy. We hypothesize that many surgical patients currently receiving radiation therapy may be clinically observed without adjuvant therapy. Methods: Patients with measurable cfHPVDNA and clinically resectable HPVOPSCC will undergo TORS resection of tumors and neck dissection. Patients with undetectable cfHPVDNA at 3 weeks post-op will be allocated to low or high-risk treatment protocol groups. The low risk group consists of patients with <4 positive lymph nodes, ≤2 mm extranodal extension (ENE), and perineural invasion (PNI) or lymphovascular invasion (LVI) alone. The high-risk group is made up of patients with ≥4 positive lymph nodes, gross ENE, positive margins, N2c disease and/or the combination of both PNI and LVI. The low-risk group will be allocated to an observation arm, while the high-risk group will receive 46 Gy of adjuvant radiotherapy and weekly cisplatin therapy. The primary outcome of interest is 2-year disease recurrence with secondary outcomes of 2-year disease free survival, locoregional control, overall survival, and quality of life measures. A sample of 126 patients in the low-risk group and 73 patients in the high-risk group will be required to evaluate non-inferiority to the standard of care. Discussion: This study will provide much needed recurrence and survival data for patients that undergo primary TORS followed by observation or de-escalated adjuvant therapy. Additionally, it will help delineate the role of cfHPVDNA in the risk stratification of patients that undergo treatment de-intensification.

Sex-Related Differences in Outcomes for Oropharyngeal Squamous Cell Carcinoma by HPV Status.

Background: Overall survival for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) has differed by sex, but little is known regarding cancer-specific outcomes. We assessed the independent association of sex with cancer-specific survival in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: We identified 14,183 patients from the Surveillance, Epidemiology, and End Results (SEER) program with OPSCC and tumor HPV status. We used Kaplan-Meier methods to compare overall survival (OS) and OPSCC-specific survival (HNCSS) by patient sex and by tumor HPV status. We then separately fit multivariable survival and competing risk models evaluating the association of sex on these outcomes by tumor HPV status and stratified by the use of guideline-concordant OPSCC treatment. Results: A total of 10,210 persons with HPV-positive tumors (72.0%) and 3,973 with HPV-negative tumors (28.0%) were identified. A larger proportion of women had HPV-negative tumors (24.0%) versus HPV-positive tumors (13.2%; p < 0.001). Women with HPV-positive tumors were less likely to receive guideline-concordant treatment compared to men. In unadjusted survival analyses, women did not differ in OS or HNCSS compared to men for HPV-positive tumors but had worse OS and HNCSS for HPV-negative tumors. After adjustment, men and women with HPV-positive OPSCC did not differ in OS or HNCSS. However, women with HPV-negative tumors faced worse overall survival (hazard ratio (HR) 1.15, 95% CI 1.02-1.29) that persisted even after stratifying for stage-appropriate treatment (HR 1.28, 95% CI 1.11-1.47). Conclusions: Women with HPV-positive OPSCC had similar survival outcomes compared to men, but those with HPV-negative tumors have worse overall and cancer-specific survival.

Impact of preoperative and intraoperative management on outcomes in osteoradionecrosis requiring free flap reconstruction.

BACKGROUND: Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and outcomes. METHODS: Multi-institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260). RESULTS: Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30-day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04). CONCLUSION: Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.

The Price of Otologic Procedures: Variation in Markup by Surgical Procedure and Geography in the United States.

OBJECTIVE: To characterize and analyze variation in price markup of seven common otologic surgeries by procedure and geographic region. STUDY DESIGN: Retrospective Analysis of the Centers for Medicare and Medicaid Services database of 2017 Medicare Provider Utilization and Payment Public File. SETTING: Inpatient and outpatient centers delivering Medicare-reimbursed services. PATIENTS: Full sample of patients undergoing procedures with Medicare fee-for-service final action claims during 2017. INTERVENTIONS: Seven procedures (myringotomy, tympanoplasty, mastoidectomy, tympanomastoidectomy stapedotomy/stapedectomy, cochlear implant, bone-anchored hearing aid). MAIN OUTCOME MEASURES: Markup ratio (MUR) is defined as the ratio of total charges to Medicare-allowable-costs; Variation in MUR was measured using coefficient of variation (CoV). RESULTS: Among all providers, the median MUR was 2.4 (interquartile range: 1.9-3.1). MUR varied significantly by procedure, from 2.3 for myringotomy to 8.7 for mastoidectomy (p < 0.01). MUR also varied significantly within procedure, with the least variation found in myringotomy (CoV = 0.46), and the greatest in cochlear implants (CoV = 0.92). Using the national average as baseline, MUR varied 71% between states, ranging from 1.75 to 6.24. Within the same state, significant variation was also noted, varying by 4% (CoV = 0.04) in Montana compared with 138% (CoV = 1.38) in Pennsylvania. MUR was not significantly correlated with patient comorbidity or Centers for Medicare and Medicaid Services risk scores. CONCLUSIONS: There was significant variation in the price of otologic surgery across geographic regions and procedures. The MUR for otology is lower or comparable to that reported in other surgical fields.

Local infusion of ropivacaine for pain control after osseous free flaps: Randomized controlled trial.

BACKGROUND: Donor site pain after osteocutaneous free flap surgery contributes to postoperative morbidity and impairs recovery. We evaluated the efficacy of local infusion of ropivacaine for treating donor-site pain after surgery. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of patients undergoing osteocutaneous fibula or scapular tip free flaps for head and neck reconstruction at Mount Sinai Hospital. Patients were randomized to receive local infusion of ropivacaine or saline. We compared Visual Analog Scale pain scores for donor-site specific pain 48 hours after surgery. RESULTS: There were 8 fibular free flap and 10 scapular free flap reconstructions. Average donor-site pain scores were 29 ± 22 and 31 ± 28 mm (P = .88) for placebo and ropivacaine arms, respectively. The trial was stopped after the planned interim analysis for futility of the intervention. CONCLUSIONS: Local infusion of ropivacaine did not affect donor-site specific pain scores in this population. ClinicalTrials.gov Identifier: NCT03349034.

Lymph Node Ratio in HPV-Associated Oropharyngeal Cancer: Identification of a Prognostic Threshold.

OBJECTIVE: To evaluate the utility of lymph node ratio (LNR) as a prognostic factor for survival and recurrence in surgically treated patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective cohort study. METHODS: In this retrospective cohort study of a tertiary healthcare system in a major metropolitan area, we reviewed 169 consecutive patients with HPV-related OPSCC treated using transoral robotic surgery. Univariable and multivariable Cox proportional hazards regression analysis with stratified models were used to compare LNR with other traditional clinicopathologic risk factors forrecurrence and survival. An LNR cutoff was found using the minimal P approach. RESULTS: Multivariable Cox regression models showed that each additional percentage increase in LNR corresponded to an adjusted hazard ratio (HR) of 1.04 (confidence interval [CI] 1.02-1.07). LNR was more significant when adjusted for adequate lymph node yield of ≥ 18 nodes (HR 5.05, 95% confidence interval [CI] 1.38-18.47). The minimal P generated cutoff point at LNR ≥ 17% demonstrated a HR 4.34 (95% CI 1.24-15.2) for disease-free survival. CONCLUSION: For HPV-related OPSCC, continuous LNR and an LNR threshold of 17% could be helpful in identifying recurrent disease in addition to measures such as lymph node number alone. LEVEL OF EVIDENCE: 4.

Prognostic role of human papilloma virus status in hypopharyngeal squamous cell carcinoma.

OBJECTIVE: Although the prognostic role of human papilloma virus (HPV) status in oropharyngeal head and neck squamous cell carcinoma (SCC) is well established, growing evidence shows that there may be a prognostic role for HPV status in hypopharyngeal SCC. The objective of this study was to determine the prognostic role of HPV status in hypopharyngeal SCC. METHODS: We performed a retrospective, population-based analysis of 1934 adult patients with HNSCC diagnosed between 2010-2016 and treated with a combination of surgery and/or radiotherapy, with or without chemotherapy, and a subset of 641 patients with hypopharyngeal SCC and known HPV status included in the Surveillance, Epidemiology, and End Results (SEER) Head and Neck with HPV Status Database. Patient data were used to determine the adjusted 2-year cancer-specific survival (CSS) and overall survival (OS) for the entire cohort and the specific subgroup of hypopharyngeal cancer patients with known HPV status. RESULTS: Of the 1934 hypopharynx SCC cases, HPV status was unknown in 1294 (66.9%), and 167 (8.6%) were HPV positive; among hypopharynx cases with known HPV status, 21.6% were HPV positive. In models adjusting for sex, age, race/ethnicity, marital status and stage, patients with HPV-positive hypopharyngeal tumors had improved CSS compared with patients with HPV-negative tumors (CSS: HR: .57, 95% CI = .38 to .86, P = .008; OS: HR: .49, 95% CI = .34 to .71, P = <.001). CONCLUSION: Our findings in a large cohort of hypopharyngeal SCC with known HPV status and cancer-specific survival support the hypothesis that HPV has a prognostic role in hypopharyngeal cancer. Consideration should be given to increased testing for HPV in hypopharyngeal SCC. LEVEL OF EVIDENCE: 4.

2-Octyl cyanoacrylate to prevent salivary fistula formation following oral cavity microvascular reconstruction: A prospective trial.

BACKGROUND: Salivary fistulas remain a significant problem in patients undergoing major head and neck reconstructive surgery. Surgical sealants have become increasingly used in cutaneous and non-cutaneous wound closure, providing a barrier to fluids/gases and promoting healing. The purpose of this study was to determine the efficacy of a common surgical sealant, 2-Octyl Cyanoacrylate (2-OCA, Dermabond®), in the prevention of salivary fistulas following free flap reconstruction of the oral cavity. METHODS: In this non-randomized, single arm prospective trial, patients undergoing free flap reconstruction of gravity-dependent oral cavity defects were recruited. Application of 2-OCA was performed along flap inset suture lines at the time of surgery. Prospectively collected trial data were propensity score matched to a control cohort to compare outcomes. Data collected include demographics, medical co-morbidities, previous treatments, primary tumor site, and subsites reconstructed. The primary outcome measure was rate of salivary fistula formation. Secondary outcomes were time to development of leak and percentage of patients tolerating oral feeding at one month post-operatively. RESULTS: In the 46 propensity score matched pairs, eight (17.4%) out of 46 patients in the 2-OCA prospective cohort and seven (15.2%) out of 46 patients in the control cohort developed postoperative salivary fistulas within the one-month study interval (p = 1.00). The average time to postoperative leak in the 2-OCA group was 12.5 days versus 7.1 days in the control cohort (p = 0.10). In the 2-OCA group, 30 (65.2%) patients were tolerating regular diet at one month post-operatively compared to 33 (71.7%) in the control cohort (p = 0.65). CONCLUSION: Salivary fistula rates after application of a 2-OCA surgical sealant were not improved compared to a control cohort in this single institutional trial. There are several surgical sealants available, each with varying elasticity and adhesiveness. Future studies are needed to identify surgical sealants that are able to provide sufficient strength and adhesion to seal closures and combat corrosive saliva, but elastic enough to handle motion related tension during swallowing and post-operative movements in the head and neck.

Neutrophil-to-lymphocyte ratio as a prognostic indicator for overall and cancer-specific survival in squamous cell carcinoma of the head and neck.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker that is correlated with systemic inflammation and poor prognosis in solid tumors. We investigated the value of NLR in predicting survival in a large population of head and neck cancer patients in the United States. METHODS: We performed a retrospective cohort study of Veterans Affairs patients with head and neck squamous cell carcinoma (HNSCC) diagnosed between January 2000 and December 2017. We compared 5-year overall survival and cancer-specific survival for different NLR tertiles using cox proportional hazards modeling with adjustment for covariates. RESULTS: The primary cohort consisted of 14 644 subjects of which 99% were male. Relative to patients with NLRs in the lower tertile, patients with NLRs in the top tertile had an 71% increased hazard of all-cause mortality (P < .001) and 44% increased hazard of cancer-specific mortality (P < .001) at 5 years. CONCLUSIONS: Elevated NLR in HNSCC confers a poor prognosis.

Infection Rates After Microlaryngeal and Open Phonosurgery: The Role of Postoperative Antibiotics.

OBJECTIVE: Although it is known that the airway has bacterial contamination that seeds the surgical site during microlaryngeal surgery, literature on the use of postoperative antibiotics is lacking. We performed a retrospective analysis of open phonosurgical and phonomicrosurgical cases at a single institution to assess whether use of postoperative antibiotics impacts the incidence of surgical site infections (SSI). METHODS: In this retrospective cohort study, we reviewed 228 phonomicrosurgery and 53 open phonosurgery cases performed for benign diseases. Surgeries were performed by two laryngologists between February 2016 and August 2018. The surgeons differ in their postoperative antibiotic regimens: no antibiotics versus a 5- to 7-day postoperative course. Data collected include demographics, medical comorbidities, type of benign laryngeal disease, and surgical procedure. The primary outcome measure was postoperative infection, defined as the patient requiring a new prescription for antibiotics, an extended course of antibiotics, or any mention of infection at follow-up/emergency visits within the first month postoperatively. RESULTS: The overall rate of SSI was 3.1% and 0% for phonomicrosurgery and open phonosurgery cases, respectively. For phonomicrosurgery, there was no difference in the rate of SSI for patients who received or did not receive antibiotics perioperatively: 2.9% versus 3.2% (P = 0.99). Similarly, there was no difference in the infection rate for open phonosurgical cases. CONCLUSION: Infection rates after endoscopic and open phonosurgery are low. In this study, we found no evidence to suggest a protective effect associated with postoperative use of antibiotics. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1128-1131, 2020.

Thirty-Day Readmission and Prolonged Length of Stay in Malignant Otitis Externa.

OBJECTIVES: To determine independent risk factors for 30-day readmission, prolonged length of stay (PLOS), and discharge to a rehabilitation facility for those with malignant otitis externa. METHODS: Retrospective cohort study of patients hospitalized with malignant otitis externa (International Classification of Diseases, 9th edition, code 380.14) in the Nationwide Readmissions Database (2013-2014). Overall and disease-specific complication and mortality data were analyzed using chi-squared and multivariate analysis. RESULTS: There were 1267 cases of malignant otitis externa extracted. A PLOS of ≥8 days (90th percentile) was found in 14.2% (n = 180) of patients, and 13.7% (n = 174) were discharged to a facility. Patients were readmitted within 30 days at a rate of 12.5% (n = 159). The overall rates of uncomplicated and complicated diabetes were found to be 42.1% and 17.8%, respectively. Factors independently associated with PLOS included undergoing a surgical procedure (odds ratio [OR] 2.08, P < .001), and having central nervous system complications (OR 3.21, P < .001). Independent risk factors for disposition to a facility included nutritional deficiency (OR 1.91, P = .029), PLOS (OR 4.61, P < .001), and age 65-79 years (OR 6.57, P = .001). Readmission was independently linked to PLOS (OR 3.14, P < .001). Diabetes was not an independent risk factor for any outcome. CONCLUSIONS: Thirty-day readmission, PLOS, and ultimate discharge to a rehabilitation facility were common and closely intertwined. Despite the classic association between diabetes and malignant otitis externa, diabetes was not an independent risk factor for any of our outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2220-2228, 2020.

National 30-day readmission and prolonged length of stay after vestibular schwannoma surgery: Analysis of the Nationwide Readmissions Database.

PURPOSE: To determine the risk factors for unanticipated readmission, prolonged index admission, and discharge to a facility after vestibular schwannoma surgery. MATERIALS AND METHODS: Retrospective cohort study of those undergoing surgery for vestibular schwannoma in the Nationwide Readmissions Database (2013-2014). Main outcome measures included readmission rate, length of stay, discharge destination. RESULTS: There were 4585 cases identified. The overall unanticipated readmission rate was 8.1%, and 9.1% had a prolonged length of stay (PLOS) of ≥7 days. Mean and median LOS were 4.63 and 4.00 days, respectively, and >90% of patients were discharged after 7 days. Disposition to a facility occurred in 6.7% of cases. Teaching hospitals were protective against unintended readmission (odds ratio [OR] 0.44, p < .001). Major functional loss was associated with PLOS (OR 12.55, p < .001). High volume centers were associated with decreased risk of PLOS (OR 0.46, p < .001) and facility discharge (OR 0.68, p < .001). The most common readmission diagnoses included "other nervous system complications" (n = 128), cerebrospinal fluid leak (n = 71), "other postoperative infection" (n = 61), and meningitis (n = 59). CONCLUSIONS: Unanticipated readmission and prolonged LOS following vestibular schwannoma surgery are common, with varied sociodemographic, hospital, and patient factors independently associated with each. Further studies are needed to investigate targeted interventions aimed at minimizing readmission and prolonged LOS using the factors outlined above.