Faculty Bibliography

Metastatic melanoma may be included in the differential diagnosis of hyoid masses in patients with a history of melanoma. Hyoid resection is well tolerated and of diagnostic and therapeutic benefit in patients with tumors metastatic to the hyoid bone.

BACKGROUND:The prevalence of survivors of oropharyngeal cancer (OPC) is increasing due to improved survival for individuals with human papillomavirus (HPV)-related disease. Although elderly survivors of OPC are known to have a high burden of comorbidities, to the authors' knowledge it is unknown how this compares with a similar cohort without a history of cancer. METHODS:The current retrospective, cross-sectional study included individuals with a first incident primary diagnosis of OPC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases and matched controls. The baseline prevalence and subsequent incidence of comorbid conditions were identified. The association between comorbidity and overall survival was evaluated. RESULTS:A total of 2497 eligible patients with OPC were matched to 4994 noncancer controls. Baseline comorbidity was higher in cases (Charlson Comorbidity Index >0 for 48.5% of cases vs 35.8% of controls). At 5 years, cases were more likely than controls to develop comorbidities. Survivors of OPC were at high risk (≥20% cumulative prevalence by 5 years) of developing several comorbidities, including cardiovascular diseases, cerebrovascular disease, chronic obstructive pulmonary disease, and tobacco abuse, and were at moderately high risk (10%-19% cumulative prevalence) of developing other conditions including carotid artery occlusive stroke, alcohol abuse, depression, and anxiety. In both cases and controls, the presence of the majority of comorbidities either at the time of diagnosis or during the follow-up period was associated with worse survival. CONCLUSIONS:Patients with OPC have a higher comorbidity burden compared with matched controls, both at baseline and during survivorship, the majority of which are associated with decreased survival. Oncologic surveillance of survivors of OPC should include screening for highly prevalent conditions.

Nasal septal perforations can cause issues of epistaxis, whistling, crusting, saddle deformity, and obstruction, which motivate patients to seek surgical repair. Numerous methods of septal perforation repair have been described, with surgical success rates ranging from 52% to 100%, but few studies address situations with concomitant septal deviation. In treating patients with septal perforation and deviation, both issues should be addressed for optimal outcomes. While routine septoplasty involves the removal of septal cartilage, septal perforation repair involves the addition of interposition grafts. The composite chondromucosal septal rotation flap harmoniously combines these seemingly conflicting goals as an effective and efficient technique for septal perforation repair. We present 3 patients successfully treated for their septal perforation and septal deviation concurrently with this technique.

BACKGROUND:The increasing incidence of human papillomavirus (HPV)-related head and neck cancer (HNC) has led to the increasing prevalence of survivors, yet to the best of the authors' knowledge the prevalence of comorbidities during the survivorship period and their effects on survival are relatively unknown. METHODS:In this retrospective cross-sectional study, individuals with a first incident primary diagnosis of HNC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases were included in the analysis and classified as patients with HPV-related or HPV-unrelated HNC. The presence of 30 comorbid conditions of interest was identified. Associations between comorbidity and treatment group as well as overall survival were evaluated. RESULTS:The study population consisted of 8025 patients with HPV-unrelated HNC and 2499 patients with HPV-related HNC. Hypertension, congestive heart failure, cerebrovascular disease, and chronic obstructive pulmonary disease all were found to be highly prevalent at the time of the cancer diagnosis and increased over time for both groups. These comorbidities were found at significantly lower rates in the HPV-related HNC population, yet were associated with an increased risk of death in both groups. The probabilities of developing cancer-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in both groups after treatment but were more likely in patients with HPV-related HNC. In both groups of patients, the presence of each comorbidity either at the time of diagnosis or during survivorship was associated with a significantly increased risk of death. CONCLUSIONS:There is a large burden of comorbidities in both patients with HPV-related and HPV-unrelated HNC, both of which are associated with decreased survival. Oncologic surveillance should not be limited to the evaluation of disease status, but also should include screening for the highly prevalent conditions associated with the risk of death.

OBJECTIVE:The aim of this study was to evaluate the prevalence of comorbidities among patients with head and neck squamous cell carcinoma (HNSCC) at the time of their cancer diagnosis and during their survivorship trajectory. The second aim was to evaluate the differences in comorbidities developed according to treatment type received. STUDY DESIGN:Retrospective cross-sectional. SETTING:SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database. SUBJECTS AND METHODS:Individuals with a first-incident primary diagnosis of HNSCC from 2004 to 2011 per the SEER-Medicare database were included in analysis. The presence or absence of 30 comorbid conditions of interest was identified during distinct periods and analyzed according to treatment with surgery alone, primary (chemo)radiation, or surgery with (chemo)radiation. RESULTS:The study population consisted of 10,524 individuals diagnosed with HNSCC, with a mean age of 74.8 years. At diagnosis, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and diabetes were the most prevalent comorbidities, and they increased over time. The probability of developing treatment-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in the short and long term following treatment ( P < .05). By 5 years from cancer diagnosis, patients were most likely to have newly diagnosed hypertension, dysphagia, anemia, and weight loss. Primary surgery alone was associated with a lower risk of diagnosis with these treatment-related comorbidities, as compared with treatments involving radiation therapy and/or chemotherapy in the primary or adjuvant settings ( P < .05). CONCLUSIONS:There is a large burden of comorbidities among patients following HNSCC treatment, which warrant clinical attention during surveillance.

OBJECTIVES:Preoperative fine needle aspiration (FNA) of parotid lesions often is used in the initial evaluation of parotid masses, but its role in guiding surgical decision making remains unclear, in part due to varying diagnostic accuracy reported. We sought to evaluate the role of preoperative FNA in detection of malignancy and impact on surgical management. STUDY DESIGN:Retrospective study. METHODS:The medical records of patients who underwent parotidectomy at a single tertiary medical center were reviewed from 2000 to 2015. Patients who had a preoperative FNA comprised the study cohort. RESULTS:A total of 1,074 consecutive patients underwent parotidectomy during the study period; of those, 477 had a preoperative FNA. FNA was nondiagnostic in 26 cases. There were 29 false positives (6.4%), 26 false negatives (5.8%), 122 true positives (27.1%), and 274 true negatives (60.8%). The sensitivity and specificity of FNA were 82.4% and 90.4%, respectively, with a positive predictive value of 80.8% and a negative predictive value of 91.3%. The overall accuracy of preoperative FNA was 87.8%. The preoperative FNA resulted in a change in the surgical plan in 85 (18.9%) cases. In 66 of these cases (78%), surgery was extended to include neck dissection at time of resection. In 10 cases, FNA led to surgical management over surveillance. In 11 cases, FNA downgraded the extent of surgery planned to an excisional biopsy. CONCLUSION:Preoperative FNA is a valuable adjunct in the surgical management of parotid lesions, with high specificity for the detection of malignant disease. LEVEL OF EVIDENCE:4. Laryngoscope, 128:398-402, 2018.

Objective To determine the impact of unilateral vagal sacrifice for vagal schwannoma on postoperative swallowing function. Study Design Case series, chart review. Setting Academic medical institution. Subjects and Methods Ten patients underwent vagus nerve sacrifice for vagal schwannoma resection. Archived pathology records dating from 1985 through 2012 at our institution were retrospectively queried for cases of vagal schwannoma with vagus nerve sacrifice. Medical records were abstracted for demographic and disease information as well as cranial nerve and swallowing function. Preoperative and postoperative cranial nerve function, subjective and objective measures of swallowing function, Functional Oral Intake Scale (FOIS) level, and need for vocal fold medialization were variables collected. Data were analyzed with summary statistics. Results The patients who underwent vagal sacrifice for vagal schwannoma at our institution had a mean age of 42.3 years (median, 44 years; range, 15-63 years) and follow-up of 35.6 months (median, 9 months; range, 1-115 months). Most presented with no preoperative cranial nerve deficit or difficulty swallowing. Immediately postoperatively, 90% had a vagus nerve deficit, but 50% had no subjective difficulty swallowing, and 70% had a FOIS level of 7 at postoperative hospital discharge. Within 1 month after surgery, 70% had normal swallowing function according to a modified barium swallow study. A full diet was tolerated by mouth within an average of 2.7 days (median, 2 days; range, 1-6 days) after surgery in this cohort. Seventy percent required vocal fold medialization postoperatively for incomplete glottic closure. Conclusion Vagal nerve sacrifice during resection of vagal schwannoma can be performed with normal postoperative swallowing function.

Comparison of tumors from The Cancer Genome Atlas (TCGA) reveals that head and neck squamous cell carcinomas (HNSCC) harbor the most frequent genomic amplifications of Fas-associated death domain (FADD), with or without Baculovirus inhibitor of apoptosis repeat containing BIRC2 (cIAP1), affecting about 30% of patients in association with worse prognosis. Here, we identified HNSCC cell lines harboring FADD/BIRC2 amplifications and overexpression by exome sequencing, RT-PCR, and Western blotting. In vitro, FADD or BIRC2 siRNA knockdown inhibited HNSCC displaying amplification and increased expression of these genes, supporting their functional importance in promoting proliferation. Birinapant, a novel SMAC mimetic, sensitized multiple HNSCC lines to cell death by agonists TNFα or TRAIL and inhibited cIAP1>XIAP>IAP2. Combination of birinapant and TNFα induced sub-G0 DNA fragmentation in sensitive lines and birinapant alone also induced significant G2-M cell-cycle arrest and cell death in UM-SCC-46 cells. Gene transfer and expression of FADD sensitized resistant UM-SCC-38 cells lacking FADD amplification to birinapant and TNFα, supporting a role for FADD in sensitization to IAP inhibitor and death ligands. HNSCC varied in mechanisms of cell death, as indicated by reversal by inhibitors or protein markers of caspase-dependent apoptosis and/or RIPK1/MLKL-mediated necroptosis. In vivo, birinapant inhibited tumor growth and enhanced radiation-induced TNFα, tumor responses, and host survival in UM-SCC-46 and -11B xenograft models displaying amplification and overexpression of FADD+/- BIRC2 These findings suggest that combination of SMAC mimetics such as birinapant plus radiation may be particularly active in HNSCC, which harbor frequent FADD/BIRC2 genomic alterations. Cancer Res; 76(18); 5442-54. ©2016 AACR.

PURPOSE/OBJECTIVE:Head and neck squamous cell carcinomas exhibit variable sensitivity to inhibitors of the PI3K/mTOR pathway, an important target of genomic alterations in this cancer type. The mitogen-activated protein kinase kinase (MEK)/ERK/activator protein 1 (AP-1) and nuclear factor-κB (NF-κB) pathways are also frequently co-activated, but their roles in resistance mechanisms to PI3K/mTOR inhibitors and as therapeutic targets in head and neck squamous cell carcinoma (HNSCC) are not well defined. EXPERIMENTAL DESIGN/METHODS:We determined the IC50s of dual PI3K/mTOR inhibitor PF-05212384 (PF-384) by XTT assays in 14 HNSCC lines with PI3K/Akt/mTOR cascade alterations. In two resistant models, we further characterized the molecular, cellular, and in vivo attributes and effects of combining PF-384 with MEK inhibitor PD-0325901 (PD-901). RESULTS:PF-384 IC50s varied between 0.75 and 133 nmol/L in 14 HNSCC lines with overexpression or mutations of PIK3CA, and sensitivity correlated with increased phospho-AKT(T308/S473). In resistant UMSCC-1 and -46 models, PF-384 increased G0-/G1-phase accumulation but weakly induced sub-G0 cell death. PF-384 inhibited direct targets of PI3K/mTOR, but incompletely attenuated co-activated ERK and UMSCC-1 xenograft growth in vivo. PD-901 strongly inhibited MEK/ERK targets, and the combination of PF-384 and PD-901 inhibited downstream NF-κB and AP-1 transactivation, and IL8 and VEGF production in vitro. PD-901 potently inhibited tumor growth alone and with PF384, enhanced antiproliferative, apoptotic, and anti-angiogenesis activity in vivo. CONCLUSIONS:PI3K/mTOR inhibitor PF-384 exhibits variable activity in a panel of HNSCC cell lines with differing PIK3CA expression and mutation status. MEK inhibitor PD-901 overcomes resistance and enhances antitumor effects observed with PF-384 in vivo.