ED visits, hospital admissions and treatment breaks in head/neck cancer patients undergoing radiotherapy.

Objectives: Radiation therapy (RT) is an integral part of treatment of head/neck cancer (HNC) but is associated with many toxicities. We sought to evaluate sociodemographic, pathologic, and clinical factors associated with emergency department (ED) visits, hospital admissions (HA), and RT breaks in HNC patients undergoing curative-intent RT. Methods: We completed a Level 3 (Oxford criteria for evidence-based medicine) analysis of a cohort of HNC patients who underwent curative-intent RT at our institution from 2013 to 2017. We collected demographic characteristics and retrospectively assessed for heavy opioid use, ED visits or HA during RT as well as RT breaks. Treatment breaks were defined as total days to RT fractions ratio ≥1.6. Multivariable stepwise logistic regression analyses were done to determine the association of various sociodemographic, pathologic, and clinical characteristics with ED visits, HA and RT treatment breaks. Results: The cohort included 376 HNC patients (294 male, 82 female, median age 61). On multivariable analysis, significant factors associated with ED visits during RT were heavy opioid use and black race. Receipt of concomitant chemotherapy was the only factor associated with hospital admissions during RT. Advanced age, lower socioeconomic class, glandular site, and receipt of chemotherapy were all independently associated with RT breaks. Lower cancer stage and lack of substance abuse history were independently associated with lack of treatment breaks. Conclusion: HNC patients with factors such as heavy opioid use, Black race, receipt of concomitant chemotherapy, and lower socioeconomic class may require closer monitoring during RT.

Redefining Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma.

OBJECTIVE: Perineural invasion (PNI) negatively affects disease-specific survival in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC). We aim to analyze the prognostic implications of PNI-related features. STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary care hospital. METHODS: Retrospective chart review was performed on 104 patients diagnosed with HNcSCC between January 2011 and October 2019 who underwent resection, parotidectomy, and neck dissection with more than 1 year of follow-up. PNI was classified as incidental (identified on histopathology alone) or clinical (present on radiography and/or physical exam). Primary outcome measures were overall survival and disease-free survival (DFS). Kaplan-Meier analysis, logistic regression, and Cox regression were performed. RESULTS: The overall 5-year DFS was 57.9%. Sixty-one patients had PNI. On histopathology, 28 lesions showed complete nerve encirclement, 10 involved >5 nerves, and 12 involved named nerves. Patients with facial weakness (P = .026) and positive margins (P = .0029) had a higher likelihood of histopathologic PNI, and positive margins retained significance on multivariable analysis (P = .0079). Worse DFS was seen in patients with PNI (P = .004), advanced tumor stage (P = .049), positive margins (P = .014), and >5 nerves involved (P = .0061). Furthermore, histopathologic PNI was a predictor of DFS (hazard ratio [HR], 3.07; 95% CI, 0.33-1.38; P = .0061) overall and in the clinical PNI cohort (HR, 3.43; 95% CI, 1.65-7.10; P = .00091). CONCLUSION: DFS was significantly worse in patients with PNI, facial nerve weakness, advanced T stage, positive margins, and multiple nerve involvement. Further characterization of PNI features may help improve prognostic predictions and identify patients who may benefit from more aggressive treatment.

Opioid use patterns in patients with head and neck cancer receiving radiation therapy: Single-institution retrospective analysis characterizing patients who did not require opioid therapy.

BACKGROUND: We had previously analyzed the variables that determine the rates of opioid use at 1-year postradiotherapy in patients with head and neck cancer. Here we analyze the variables associated with opioid abstinence during and in the 12 months after radiotherapy at our institution. METHODS: We identified a cohort of patients with head and neck cancer who received radiotherapy as part of curative treatment at our institution. Logistic regression analyses were performed to determine socioeconomic and clinical factors associated with opioid abstinence. RESULTS: The cohort included 376 patients. On multivariable analysis, patients from an upper-income class (p = 0.004), black race (p = 0.004), older (p = 0.008), with dependent children (p < 0.001) or receiving surgery (p = 0.002) were more likely to abstain from opioids, while patients using analgesic mouthwash (p = 0.009) or higher pain scale (p = 0.002) were less likely. CONCLUSION: Socioeconomic and treatment characteristics are associated with opioid abstinence during and following radiation treatment in patients with head and neck cancer.

High-Risk Cutaneous Squamous Cell Cancer of the Head and Neck: Risk Factors for Recurrence and Impact of Adjuvant Treatment.

OBJECTIVES: The behavior of advanced cutaneous squamous cell carcinoma of the head and neck (HNcSCC) remains poorly understood, with highly variable risk factors and a paucity of data for adjuvant treatment. The objective of our study was to review the oncologic outcomes of patients with high-risk HNcSCC treated with surgery and to identify risk factors for treatment failure. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective review of patients treated for HNcSCC with definitive surgery involving at least parotidectomy and neck dissection at a tertiary care academic center from 2011 to 2017 was conducted. The primary outcome was disease-free survival (DFS). RESULTS: One-hundred four patients with a median age of 68 years (range = 42-91 years) were reviewed. Twenty-one patients were treated with surgery alone, 45 patients underwent adjuvant radiotherapy (RT), and 38 patients underwent adjuvant chemoradiotherapy (CRT). The 2-year DFS for patients treated with surgery, surgery + RT, and surgery + CRT were 71%, 65%, and 58%, respectively, with no significant difference between the groups (P = .70). On multivariate analyses, tumor size (P = .006) and perineural invasion (PNI, P = .04) independently predicted recurrence. The addition of chemotherapy did not appear to improve DFS, neither for those patients with extranodal extension and/or positive margins (P = .93) nor for the entire cohort (P = .43). CONCLUSIONS: Advanced HNcSCC has a high recurrence rate despite adjuvant treatment. Tumor size >2 cm was a strong independent risk factor for recurrence. Out of the traditional mucosal HNcSCC risk factors, PNI was most strongly associated with worse DFS. There was no observed survival benefit to the addition of chemotherapy. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E136-E143, 2021.

CD44 and associated markers in oral rinses and tissues from oral and oropharyngeal cancer patients.

OBJECTIVES: Oral and oropharyngeal squamous cell carcinoma (OOPSCC) is a debilitating disease. Salivary rinses contain soluble tumor markers including CD44 (solCD44) and total protein (TP) that may aid detection and prognosis of these aggressive tumors. Here we aim to examine the relationship between these salivary biomarkers and tissue markers p16 and CD44 and determine whether these markers can predict progression-free survival (PFS) and overall survival (OS). MATERIALS AND METHODS: Prospective study to update biomarkers using oral rinses and tissues from OOPSC patients enrolled between 2007 and 2012 at an academic tertiary referral center. 64 cases from a 300-subject case-control study with archived tissue for immunohistochemistry were included. RESULTS: 82.8% were male, 84.4% were ever smokers, 70.3% had disease stage T3-T4, and 57.8% presented with nodal disease. Nineteen patients (25%) were p16 positive. The group with strong tissue CD44 expression in membrane and cytoplasm had higher levels of solCD44 (mean 10.73 ng/ml) than other groups (5.47 ng/ml) (p = 0.033). TP levels were significantly reduced in oral rinses from subjects with p16 universal gross tumor tissue staining (mean 0.80 vs. 1.08 mg/ml; p = 0.039). On multivariate analysis, universal CD44 gross tissue staining and TP levels ≥ 1 mg/ml demonstrated poorer PFS, with the latter also affecting OS. Poorer survival was associated with soluble CD44 ≥ 5.33 ng/ml and TP ≥ 1 mg/ml. CONCLUSIONS: Direct associations were found between high solCD44 levels and strong membrane and cytoplasmic CD44 expression, and between high TP levels and peripheral/mixed p16 gross staining. Poorer PFS and OS are significantly associated with higher levels of solCD44 and protein in oral rinses.

Single-cell analysis of olfactory neurogenesis and differentiation in adult humans.

The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying input to the olfactory bulbs of the brain. Using single-cell RNA sequencing analyzing 28,726 cells, we identified neural stem cell and neural progenitor cell pools and neurons. Additionally, we detailed the expression of 140 olfactory receptors. These data from the olfactory neuroepithelium niche provide evidence that neuron production may continue for decades in humans.

Long-term opioid use in curative-intent radiotherapy: One-Year outcomes in head/neck cancer patients.

BACKGROUND: No study has determined the incidence of long-term opioid use, or risk factors for long-term use, ≥1 year after radiotherapy. METHODS: Medical records of 276 head/neck cancer patients were retrospectively assessed for persistent opioid use 1-year after curative-intent radiotherapy. Numerous potential risk factors were assessed and the physicians' documented reasons for continued use were qualitatively categorized as suspected opioid use disorder (OUD) or as medically indicated for control of ongoing pain. RESULTS: Of note, 20 of 276 patients continued using opioids long-term. High maximum opioid dose and the use of opioids and/or psychotropics/non-opioid analgesics at the radiation oncology intake visit were associated with this outcome. Three patients continued due to suspected OUD and 17 due to medical indications. CONCLUSION: Of note, 7.2% of patients developed long-term opioid use, which was associated with high maximum opioid dose and early initiation of opioids and/or psychotropics/non-opioid analgesics. Physicians cited medical indications as the primary reason for continued use.

The use of dehydrated amniotic membrane allograft for augmentation of dural repair in transsphenoidal endoscopic endonasal resection of pituitary adenomas.

BACKGROUND: In transsphenoidal endoscopic endonasal surgery (TEES), watertight separation of the sinonasal cavity and intracranial compartment is the primary goal of closure. However, even when meticulous closure technique is implemented, cerebrospinal fluid (CSF) leaks, dural scarring, and meningitis may result. Particularly when intraoperative CSF leak occurs, materials that facilitate the creation of a watertight seal that inhibits disease transition and minimizes inflammatory response after durotomy are sought. Dehydrated amniotic membrane (DAM) allograft appears to confer these attributes as studies have shown it augments epithelialization, facilitates wound healing, and minimizes and impedes bacterial growth. We detail the use of DAM allograft to augment sellar closures after TEES. METHODS: We conducted a feasibility study, retrospectively reviewing our institution's database of TEES for resection of pituitary adenomas in which DAM was utilized to supplement sellar closure. RESULTS: One hundred twenty transsphenoidal surgery cases with DAM were used during sellar closure, with a 49.2% intraoperative CSF leak rate. Of this cohort, two patients experienced postoperative CSF leak (1.7%), and no patients developed meningitis. CSF leak rate for TEES-naïve patients was 0.9%. CONCLUSIONS: This feasibility study demonstrates that dehydrated amniotic membrane allograft can be safely utilized as an adjunct during sellar closures for TEES for pituitary adenoma resection with very low rates of CSF leak and meningitis.

Meta-analysis comparing outcomes of different transoral surgical modalities in management of oropharyngeal carcinoma.

BACKGROUND: Optimal transoral surgical modality for oropharyneal carcinoma is currently unclear. Transoral laser surgery (TLS), transoral robotic surgery (TORS), and conventional direct transoral (DT) oropharyngectomy are the main current transoral surgical modalities for oropharyngeal carcinoma. METHODS: MEDLINE was systematically searched through PubMed. Reference lists were reviewed. Random-effects models were used to combine studies within each group. Tests for heterogeneity were used to explore difference in effect size between groups in subgroup analysis. RESULTS: Nine studies (404 patients) in TORS arm, five studies (498 patients) in TLS arm, and three studies (335 patients) in DT arm were included. Early T classification (T1-T2) for TORS and DT were higher compared to TLS group (P < .001). There was no significant difference between groups in the rate of invaded margin, post-operative oropharyngeal bleeding, temporary tracheotomy, and gastrostomy dependence. CONCLUSION: The available data do not yet provide clear evidence of superiority of any one modality.

Transsphenoidal Approach for Pituitary Adenomas in Elderly Patients.

INTRODUCTION: With a rapidly expanding elderly population in the United States, the incidence of pituitary adenomas in elderly will continue to rise. In this study, we aim to evaluate the safety and efficacy of transsphenoidal endoscopic endonasal resection for pituitary adenomas in the elderly population. METHODS: A retrospective review of 131 consecutive patients who underwent transsphenoidal endoscopic endonasal resection for pituitary adenomas at the University of Miami Hospital between 2012 and 2016 was performed. Preoperative, intraoperative, and surgical outcomes were analyzed in elderly (>70 years) versus nonelderly (<70 years) patients. RESULTS: Of the 131 patients, 23 of them were >70 years (18%), of which 14 were septuagenarians and 9 were octogenarians. Elderly patients were more likely to present with vision loss (80.8% vs. 56.6%; P = 0.013) and larger tumors on imaging (2.7 ± 1.0 cm vs. 2.4 ± 1.3 cm; P = 0.042). Overall surgical and endocrinologic outcomes between the 2 groups were similar. However, patients <70 years old were more likely to have a gross total resection (86.7% vs. 65.4%; P = 0.011), as well as transient diabetes insipidus (54.3% vs. 26.9% P = 0.012) and intraoperative cerebrospinal fluid leak (83.5% vs. 58.5%; P = 0.013). However, permanent postoperative complication rates were similar including rate of permanent diabetes insipidus (4.3% elderly vs. 12.1% adult), cerebrospinal fluid leak (8.7% elderly vs. 8.4% adult), and meningitis (4.3% elderly vs. 2.8% adult). There were no medical complications or deaths in our cohort. CONCLUSION: The transsphenoidal endoscopic endonasal approach can be a safe and effective technique for resection of pituitary adenomas in patients >70 years old with appropriate patient selection.

Volumetry in the Assessment of Pituitary Adenoma Resection: Endoscopy versus Microscopy.

Background Assessment of the extent of resection after surgical resection of pituitary adenomas is most commonly reported in terms of the presence or absence of residual tumor. A quantitative comparison of volumetric resection between endonasal endoscopy (EE) and microsurgery (MS) has rarely been done. Methods A retrospective analysis was performed on a consecutive series of 154 patients with pituitary adenomas treated by the same surgeon at a single institution. We employed volumetric analysis pre- and postoperatively on two cohorts of pituitary adenoma patients treated through MS ( n = 37) versus EE approach ( n = 117). Results Volumetric analysis revealed a higher incidence of complete resection (64.4 vs. 56.8%) and mean volume reduction in the EE cohort (92.7 vs. 88.4%), although not significant. Recurrence rates were significantly lower in the EE group (7.7% vs 24.3%, p = 0.015). Subgroup analysis identified that patients with preoperative tumor volumes >1 mL were less likely to recur through EE (7.8 vs. MS: 29.6%; p = 0.0063). A higher incidence of complete resection was also noted in patients with favorable Knosp grades (0-1) (EE: 87.8 vs. MS: 63.2%; p = 0.036). Postoperative complication rates were not significantly different between both techniques. Conclusion Both microscopy and endoscopy are well-tolerated, effective approaches in the treatment of pituitary adenomas. Our series demonstrated that EE may be superior to MS in preventing tumor recurrence and achieving a complete resection in certain subsets of patients. EE provides a slight advantage in tumor control outcomes that may justify the paradigm shift to pure endoscopy at our center.

Spontaneous healing of a shredded esophagus after ACDF without direct repair.

Esophageal perforation is a catastrophic complication of anterior cervical discectomy and fusion (ACDF). While direct surgical repair has been reported as optimal for restoration of upper gut function, we present the case of a 58-year-old woman who achieved complete resolution when treated only with debridement and drainage. We find that a supportive approach, surgical management without direct repair, may play a vital role in select patient populations in order to avoid potentially long-term consequences or radical treatments, like esophageal diversion. Decisions regarding direct repair versus debridement and inspection only should be made on a case-by-case basis through a multidisciplinary approach.

Assessment of human papillomavirus awareness in association with head and neck cancer at a screening event.

OBJECTIVES/HYPOTHESIS: To assess the baseline awareness of human papillomavirus (HPV) infection as a cause of head and neck cancer (HNC) to design improved targeted screening and education efforts. STUDY DESIGN: Retrospective review of collected survey at a cancer screening event. METHODS: This was a screening event at three hospitals and one community center in Miami, Florida. Participants were recruited throughout the Greater Miami area. Descriptive statistics were used to summarize the demographic characteristics of those who were aware of HPV and those who were not. Adjusted odds ratios, odds ratios, and χ2 tests were used in statistical analysis. RESULTS: A total of 196 women and 112 men were screened across four sites, with 187 participants at hospital-based events and 124 participants at the community-based event. Forty percent of respondents had heard of HPV, and 28.0% identified HPV as a risk factor for HNC. Non-Hispanic and Hispanic respondents were 3.309 and 2.445 times, respectively, more likely than Haitian respondents to have heard of HPV. Women were 2.488 times more likely than men to be aware of HPV. College graduates were 2.268 times more likely than those with less than a college degree to be aware of HPV. Younger respondents were more likely to be aware of HPV. Of those who identified HPV as a risk factor for HNC, 95.4% also correctly identified smoking and 75.9% also correctly identified alcohol as risk factors. CONCLUSIONS: Disparities in HPV and HNC awareness were noted between gender, age, education level, and ethnicity. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:386-392, 2018.

Case of parotid mucoepidermoid carcinoma: Expanding the spectrum of von Hippel-Lindau-related neoplasms.

BACKGROUND: von Hippel-Lindau (VHL)-related tumors occurring outside the spectrum of VHL-defining tumors are rare, and mucoepidermoid carcinoma (MEC) in the setting of VHL disease has not been described. METHODS AND RESULTS: We describe a patient with confirmed VHL mutation who presented with a parotid mass and a history of 2 central nervous system (CNS) hemangioblastomas and 1 pheochromocytoma. Fine-needle aspiration (FNA) of the mass suggested a benign Warthin tumor. The mass was resected and final pathology revealed a low-grade MEC. Fluorescence in situ hybridization for the MECT1/MAML2 fusion gene frequently associated with MEC was performed and was negative. Molecular testing of tumor cells displayed a likely "second hit" VHL gene mutation. CONCLUSION: There is a possible broader role of VHL mutations in tumorigenesis beyond the development of classically described VHL-defining neoplasms. Our case also demonstrates the importance of always considering the possibility of a parotid malignancy in patients with VHL despite a benign FNA. © 2016 Wiley Periodicals, Inc. Head Neck 39: E51-E54, 2017.

Open airway reconstruction in adults: Outcomes and prognostic factors.

PURPOSE: The purpose was to assess the success of open tracheal resection and re-anastomosis for non-malignant tracheal stenosis in adults. Successful operations were defined as T-tube or tracheostomy-free status by 6months post-operatively. MATERIALS AND METHODS: Retrospective chart review was performed and data were recorded in a de-identified manner. The primary outcome was T-tube or tracheostomy-free status by 6months following tracheal resection. Clinical and demographic characteristics were evaluated as potential prognostic variables. RESULTS: Thirty-two patients met inclusion criteria, with a median age of 46. Seven patients underwent tracheal resection with primary closure, without stenting. Successful tracheal resection was defined as tracheostomy or T-tube free by 6months post-operation, and this was possible in 21 patients (66%). Eighty-two percent of patients with cricoid cartilage-sparing tracheal resection had a successful outcome, versus 30% of patients who underwent cricoid cartilage resection (HR 5.02, 95% CI 1.46-17.3; p=0.011). Patients with a history of tracheostomy-dependence were four times more likely to remain tube-dependent at 6months (HR 4.15, 95% CI 1.56-10.86; p=0.004). CONCLUSIONS: Tracheal stenosis remains a very difficult problem to treat. In our series, we confirm that patients with cricoid involvement or with a history of tracheostomy were more likely to be tube dependent at 6-months post-operation.

Complications and oncologic outcomes following elective neck dissection with salvage laryngectomy for the N0 neck.

PURPOSE: To investigate the difference in survival and complication outcomes between patients with a clinically and radiologically N0 neck who received an elective neck dissection at the time of salvage total laryngectomy compared to those who had salvage total laryngectomy alone. MATERIALS AND METHODS: A retrospective chart review was performed on 125 salvage total laryngectomy patients who were clinically and radiologically N0 preoperatively. Performance of an elective neck dissection and other factors were tested for associations with various postoperative complications, disease-free survival, and overall survival. RESULTS: Ninety-eight patients underwent elective neck dissection, of which ten had positive nodal pathology. Elective neck dissection was not significantly associated with complications or survival outcomes. Positive nodal disease was associated with worse disease-free and overall survival on multivariate analysis. CONCLUSIONS: In patients with clinically and radiologically N0 necks undergoing salvage total laryngectomy, an elective neck dissection can provide prognostic information but does not appear to be significantly associated with increased complications or improved survival.

Recruitment of underserved, high-risk participants to a head and neck cancer screening program.

OBJECTIVES/HYPOTHESIS: Early detection is essential in head and neck cancer treatment as prognosis varies greatly with stage at diagnosis. Underserved populations often present with advanced disease, and individuals with tobacco and heavy alcohol use demonstrate a higher head and neck cancer incidence. This study aims to evaluate whether various promotional methods differentially recruited behavioral risk factor positive and/or underserved populations to our screening event. STUDY DESIGN: Prospective cross-sectional study. METHODS: A hospital-based, medical student-run, free head and neck cancer screening event for 187 participants was held in April 2015. Medical campus-based, community-based, and media-based promotions were implemented to recruit participants. Event participants filled out questionnaires to determine how they were recruited, their risk-factor history, and their socioeconomic status. Prevalence of the higher-risk population across the various promotional methods was analyzed. RESULTS: Community-based promotions were significantly associated with the recruitment of participants in the underserved subgroups, namely uninsured (P = .019), unemployed (P = .006), and those with an annual household income <$20,000 (P < .001). Although not statistically significant, participants with behavioral risk factors reported a higher percentage of recruitment by media-based promotions. Campus-based promotions led to the highest absolute number, but not percentage, of higher-risk participants. CONCLUSIONS: Community-based promotions most efficiently recruit underserved guests to participate in a hospital-based head and neck cancer screening event as compared to media and campus-based promotions. Institutions interested in recruiting higher proportions of underserved guests to these screening events should consider focusing attention and allocation of resources to community-based promotions. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2699-2704, 2016.

Educational Value of a Medical Student-Led Head and Neck Cancer Screening Event.

OBJECTIVE: To evaluate improvement of medical student knowledge of head and neck cancer (HNC) through participation in HNC screening fairs run by medical students. STUDY DESIGN: Prospective cohort study of surveys assessing medical students' knowledge of HNC before and after volunteering at screening fairs. SETTING: Four screening fairs held at the University of Miami Miller School of Medicine during Oral, Head and Neck Cancer Awareness Week. SUBJECTS: Medical student screening fair volunteers. METHODS: Four HNC screening fairs were organized by medical student volunteers. All students completed a preevent survey assessing baseline knowledge and participated in an otolaryngologist-led training session about HNC and the screening examination. During the screening events, students educated guests about HNC and performed physician-guided history and physical examinations. Finally, students completed identical surveys 1 week and 3 months after the event. RESULTS: Thirty-four (n = 34) students completed the preevent surveys. At baseline, 59%, 44%, and 24% named tobacco, alcohol, and human papilloma virus as risk factors, compared with 84%, 81%, and 69% on 3 month follow-up, respectively. Out of 6 analyzed questions, the median total number of correctly answered questions improved from 2 on pretest to 5 at 3 months (P < .0001). CONCLUSION: Volunteer participation in a HNC screening program improves medical students' knowledge of HNC risk factors and symptoms. This innovative approach to students' education via participation and organization of screening events is a useful method of improving their HNC knowledge.