Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.

The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined HNSCC subtypes by their malignant and stromal composition and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis.

Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC). METHODS: To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24 hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45. RESULTS: In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1 copy/mL by POD 1 (n = 8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350 copies/mL) and remained elevated until adjuvant treatment (n = 3/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2-58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n = 9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1 mm (P = .0481) and with increasing lymph nodes involved (P = .0453) and were further associated with adjuvant treatment received (P = .0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2 months earlier than clinical detection. CONCLUSIONS: POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. LAY SUMMARY: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery. This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC. We found that ctHPVDNA levels 1 day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.

Long non-coding RNA ELDR enhances oral cancer growth by promoting ILF3-cyclin E1 signaling.

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer with a 5-year overall survival rate of 50%. Thus, there is a critical need to understand the disease process, and to identify improved therapeutic strategies. Previously, we found the long non-coding RNA (lncRNA) EGFR long non-coding downstream RNA (ELDR) induced in a mouse tongue cancer model; however, its functional role in human oral cancer remained unknown. Here, we show that ELDR is highly expressed in OSCC patient samples and in cell lines. Overexpression of ELDR in normal non-tumorigenic oral keratinocytes induces cell proliferation, colony formation, and PCNA expression. We also show that ELDR depletion reduces OSCC cell proliferation and PCNA expression. Proteomics data identifies the RNA binding protein ILF3 as an interacting partner of ELDR. We further show that the ELDR-ILF3 axis regulates Cyclin E1 expression and phosphorylation of the retinoblastoma (RB) protein. Intratumoral injection of ELDR-specific siRNA reduces OSCC and PDX tumor growth in mice. These findings provide molecular insight into the role of ELDR in oral cancer and demonstrate that targeting ELDR has promising therapeutic potential.

Opioid prescribing practices in academic otolaryngology: A single institutional survey.

OBJECTIVES: Opioids are highly addictive medications and otolaryngologists have a responsibility to practice opioid stewardship. We investigated postoperative opioid prescribing patterns among resident and attending physicians as an educational platform to underscore the importance of conscientious opioid prescribing. METHODS: This quality improvement study was designed as a cross-sectional electronic survey. Residents and attending clinical faculty members at a single academic institution were queried from February through April 2020. An electronic survey was distributed to capture postoperative opioid prescribing patterns after common procedures. At the conclusion of the study, results were sent to all faculty and residents. RESULTS: A total of 29 attending otolaryngologists and 22 residents completed the survey. Resident physicians prescribed on average fewer postoperative opioid pills than attendings. Among attendings, the largest number of opioids were prescribed following tonsillectomy (dose varied by patient age), neck dissection (12.6 pills), brow lift (13.3 pills), facelift (13.3 pills), and open reduction of facial trauma (10.7 pills). For residents, surgeries with the most postoperatively prescribed opioids were for tonsillectomy (varied by patient age), neck dissection (13.4 pills), open reduction of facial trauma (10.5 pills), parotidectomy (10.0 pills), and thyroid/parathyroidectomy (9.0 pills). The largest volume of postoperative opioids for both groups was prescribed following tonsillectomy. Attendings prescribed significantly more opioids after facelift and brow lift than did residents (p = 0.01 and p = 0.003, respectively). CONCLUSION: There was good concordance between resident and attending prescribers. Improvement in opioid prescribing and pain management should be an essential component of otolaryngology residency education and attending continuing medical education. LEVEL OF EVIDENCE: 4.

Comparison between computed tomography and ultrasound for presurgical evaluation of oral tongue squamous cell carcinoma tumor thickness.

PURPOSE: To compare the accuracy of oral tongue squamous cell carcinoma (OTSCC) tumor thickness (TT) measured on CT to intraoperative ultrasound (US) and histopathology. METHODS AND MATERIALS: Twenty-six patients with OTSCC who underwent tumor resection by a single surgeon with simultaneous intraoperative US between 3/2016 and 4/2019 were prospectively identified, and their data reviewed. TT was independently measured in 19 patients who underwent preoperative CT (cTT) by two neuroradiologists blinded to US and histological results. The confidence level of interpretation of cTT was recorded by each reader using a 5-point Likert scale. The degree of dental artifact on CT was also scored. cTT was compared to TT measured on intraoperative US (uTT) and histopathologic assessment of TT (hTT). RESULTS: OTSCC was visualized on CT in 52% (10/19) and 63% (12/19) of cases for readers 1 and 2, respectively. Mean Likert score was 0.42 for reader 1 and 0.73 for reader 2. Mean cTT of OTSCCs was 5.8 mm +/- 1.7 mm (n = 11). In comparison, mean uTT and hTT were 7.6 mm±3.5 mm and 7.1 +/- 4.2 mm, respectively. The Pearson coefficient (95% confidence interval) was 0.10 (-0.53-0.66) between cTT and hTT (n = 11) and 0.93 (0.74-0.98) between uTT and hTT. CONCLUSIONS: Preoperative CT is not reliable for assessment of TT in OTSCC compared to US and histopathology, particularly for OTSCC under 10 mm. US offers a practical complementary imaging tool with a unique role for primary tumor assessment that can aid in pre-operative planning, especially for small tumors.

Nasal and paranasal sinus mucosal melanoma: Long-term survival outcomes and prognostic factors.

OBJECTIVE: To determine prognostic factors and survival patterns for different treatment modalities for nasal cavity (NC) and paranasal sinus (PS) mucosal melanoma (MM). METHODS: Patients from 1973 to 2013 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and multivariable cox proportional hazard modeling were used for survival analyses. RESULTS: Of 928 cases of mucosal melanoma (NC = 632, PS = 302), increasing age (Hazard Ratio [HR]:1.05/year, p < 0.001), T4 tumors (HR: 1.81, p = 0.02), N1 status (HR: 6.61, p < 0.001), and PS disease (HR: 1.50, p < 0.001) were associated with worse survival. Median survival length was lower for PS versus NC (16 versus 26 months, p < 0.001). Surgery and surgery + radiation therapy (RT) improved survival over non-treatment or RT alone (p < 0.001). Adding RT to surgery did not yield a survival difference compared with surgery alone (p = 0.43). Five-year survival rates for surgery and surgery + RT were similar, at 27.7% and 25.1% (p = 0.43). CONCLUSION: Surgery increased survival significantly over RT alone. RT following surgical resection did not improve survival.

Rising incidence of late-stage head and neck cancer in the United States.

BACKGROUND: The current study was conducted to determine whether the incidence of late-stage head and neck cancer (HNC) is decreasing and to estimate the risk of late-stage HNC diagnosis based on race and sex. METHODS: Age-adjusted incidence rates for patients aged ≥18 years with stage IV HNC were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2015). Rates were stratified by race, sex, and age. Joinpoint regression estimated annual percent changes (APCs) in rates over time, and logistic regression estimated adjusted odds ratios (aORs). RESULTS: There were 57,118 patients with stage IV HNC in the current study cohort, with an average age of 61.9 years. From 2004 to 2015, the age-adjusted incidence rates for stage IV HNC significantly increased by 26.1% (6.11 per 100,000 person-years in 2004 to 7.70 per 100,000 person-years in 2015). White and Asian/Pacific Islander/American Indian/Alaska Native patients had significant increases in incidence (APC for white patients, 3.03 [P < .01] and APC for other races, 1.95 [P < .01]), whereas rates among black patients remained stable but were highest across racial groups. Incidence was higher among males compared with females. When restricted only to patients with stage IVC (metastatic) HNC, there remained a significant increase in incidence, especially for oropharyngeal cancer, which showed a 22.9% increase (0.21 per 100,000 person-years in 2004 vs 0.25 per 100,000 person-years in 2015). Despite a decreasing overall incidence of stage IV HNC in black patients (aOR, 1.28; 95% CI, 1.22-1.34) they, along with males (aOR, 3.95; 95% CI, 3.80-4.11), had significantly increased risks of being diagnosed with late-stage HNC. CONCLUSIONS: There is an increasing incidence of late-stage HNC in the United States, with male patients and black individuals faring the worst.

Impact of the Patient Protection and Affordable Care Act on cost-related medication underuse in nonelderly adult cancer survivors.

BACKGROUND: Cost-related medication underuse (CRMU), a measure of access to care and financial burden, is prevalent among cancer survivors. The authors quantified the impact of the Patient Protection and Affordable Care Act (ACA) on CRMU in nonelderly cancer survivors. METHODS: Using National Health Interview Survey data (2011-2017) for cancer survivors aged 18 to 74 years, the authors estimated changes in CRMU (defined as taking medication less than prescribed due to costs) before (2011-2013) to after (2015-2017) implementation of the ACA. Difference-in-differences (DID) analyses estimated changes in CRMU after implementation of the ACA in low-income versus high-income cancer survivors, and nonelderly versus elderly cancer survivors. RESULTS: A total of 6176 cancer survivors aged 18 to 64 years and 4100 cancer survivors aged 65 to 74 years were identified. In DID analyses, there was an 8.33-percentage point (PP) (95% confidence interval, 3.06-13.6 PP; P = .002) decrease in CRMU for cancer survivors aged 18 to 64 years with income <250% of the federal poverty level (FPL) compared with those with income >400% of the FPL. There was a reduction for cancer survivors aged 55 to 64 years compared with those aged 65 to 74 years with income <400% of the FPL (-9.35 PP; 95% confidence interval, -15.6 to -3.14 PP [P = .003]). CONCLUSIONS: There was an ACA-associated reduction in CRMU noted among low-income, nonelderly cancer survivors. The ACA may improve health care access and affordability in this vulnerable population.

Prevalence and factors associated with diagnosed depression among hospitalized cancer patients with metastatic disease.

PURPOSE: This study aimed to examine the factors associated with diagnosed depression among patients with a metastatic cancer. METHODS: We conducted a cross-sectional analysis of 39,223 hospital records from 2008 to 2013 National Inpatient Sample for patients with metastatic cancer. Diagnosed depression was defined using ICD-9-CM for major depression. Weighted, multivariable hierarchical regression model was used to examine the association between sociodemographic and clinical factors and depression among patients with a metastatic cancer. RESULTS: The prevalence of clinically diagnosed depression in patients with a metastatic cancer in our study sample was 7.3% (5.9% for males and 8.6% for females). The prevalence rate of diagnosed depression increased from 5.3 to 9.4% between 2008 and 2013. In multivariable analysis, patients were more likely to be diagnosed with depression if they were females (aOR = 1.44; 95% CI 1.25-1.66) compared to males; and had higher number of comorbidities (aOR = 1.11 per 1-unit increase in Elixhauser comorbidity score, 95% CI 1.07-1.15). In contrast, patients were less likely to be diagnosed with depression if they were blacks (aOR = 0.59; 95% CI 0.47-0.74) or other race (aOR = 0.58; 95% CI 0.47-0.72) compared with white patients. CONCLUSIONS: Women and individuals with more comorbidities were diagnosed with depression more frequently, whereas black patients were diagnosed less. Our findings could help providers to identify hospitalized patients with the higher risk of depression and screened patients with signs and symptoms of clinical depression.

What's Love Got to do with it? Marital status and survival of head and neck cancer.

OBJECTIVE: To determine whether marital status independently predicts survival in a head and neck cancer (HNC) survivor population. METHODS: In this retrospective cohort study, we analysed data from 460 adult patients (59.31 ± 11.42) years diagnosed with HNC at an academic tertiary referral centre between 1997 and 2012. Cox proportional hazards model estimated the effect of marital status on survival. RESULTS: Our study had 73% men, and 82.2% were Whites. We found an association between marital status and HNC survival. Unmarried HNC patients had a 66% increase in hazard of death compared to married patients (aHR = 1.66, 95% CI = 1.23-2.23). This was after controlling for sociodemographic variables (age, race, sex and health insurance status), social habits (tobacco and alcohol), primary anatomical subsite (oral cavity, oropharyngeal, laryngeal and others), stage at presentation (early vs. late stage) and treatment modality (surgery, surgery with adjuvant therapies, other single modality therapy and palliative care). CONCLUSIONS: Being married confers survival advantage for HNC survivors. Our finding underscores the need to recognise this aspect of survivorship. Social support should be considered part of standard care for managing HNC. There may also be need to develop other support mechanisms, especially for unmarried HNC survivors.

Plunging ranula with lingual nerve tether: Case report and literature review.

Plunging ranulas are most often treated surgically; various surgical approaches may be necessary depending on the unique characteristics of each case. Here, we present the case of a plunging ranula noted on imaging to have a cordlike tether, which was revealed intraoperatively to be the lingual nerve. This case illustrates the importance of preoperative imaging for surgical planning, and when a transcervical approach may be the best choice for plunging ranulas.

United States-based global otolaryngology surgery: A call to more horizontal sustainable efforts.

OBJECTIVE: To examine global surgery involvement among general members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and characterize international otolaryngology surgical interventions. METHODS: Data on global surgery involvement were derived from responses provided by voluntary online survey respondent members of the AAO-HNS, obtained in October 2017. These data were compared against World Bank metrics of national health expenditure and surgical specialists per capita as benchmarks for need. RESULTS: There were 362 responses (response rate of 3.7%). A large proportion of respondents reported being involved in global surgery (61.3%). Locations where respondents worked included: South America (13.3%), Central America (17.7%), Caribbean (10.2%), Europe (4.1%), Africa (16.3%), Asia (16.6%), the Middle East (4.1%), and Oceania (3.6%). A greater proportion of respondents reported traveling to locations that have lower health care expenditure per capita and lower mean number of surgical specialists per 100,000 people, according to data from the World Bank. The primary purpose of trips was most commonly surgical mission (60.3%), followed by education (37.8%), and research (1.9%). CONCLUSION: Members of the AAO-HNS are active in global surgery efforts around the world. Collaboration among members of the AAO-HNS may serve to improve long-term sustainability of these efforts.

Mucoepidermoid Carcinoma of the Parotid: Very Close Margins and Adjuvant Radiotherapy.

BACKGROUND/AIMS: The importance of adjuvant radiotherapy in patients with close margin resections for mucoepidermoid carcinoma of the parotid gland remains unclear. METHODS: Patients who underwent parotidectomy for mucoepidermoid carcinoma with or without adjuvant radiotherapy at a single academic tertiary care center from 2000 to 2014 were identified. Included patients had negative but close (≤2 mm) surgical margins without other high-risk histopathological factors including advanced T-stage, positive nodal disease, lymphovascular or perineural invasion, or high-grade histology. RESULTS: Nineteen patients were identified, of whom 15 (79%) were observed postoperatively, while 4 (21%) underwent adjuvant radiotherapy. There were no significant differences in extent of parotidectomy, elective neck dissection, T staging, or tumor size between patients who were observed and those undergoing adjuvant radiation. There were no locoregional or distant recurrences in any patients at a mean follow up 74.3 months. Patients undergoing adjuvant radiation, however, had significantly more intermediate-grade as compared to low-grade histology (75% vs. 13%, difference 62%, 95% CI 4% to 100%). CONCLUSIONS: Patients with negative but close (≤2 mm) surgical margins without other high-risk histopathological factors have excellent long-term locoregional control with surgery alone. The effects of adjuvant radiotherapy for those who have intermediate-grade disease remain uncertain.

Composite Nasoseptal Flap for Palate Reconstruction.

Palatal fistulae represent a pathological connection from the oral cavity through the hard or soft palate to the nasal cavity and can present a significant reconstructive dilemma. Surgical correction of palatal fistulae is often limited by prior treatment, including ablative procedures and radiotherapy, or previous reconstructive attempts. In light of these challenges, the nasoseptal flap represents an excellent adjacent source of vascularized tissue which may be suitable for palatal fistula repair with minimal donor site morbidity, low associated risks, and a short recovery period. The purpose of this study was to fully understand the potential utility of this reconstructive option, including the ability to harvest a composite flap including both septal cartilage and contralateral mucoperichondrium. In this single institution prospective study consisting of a series of 5 cadaver dissections, primary outcome measures were the anterior reach of the flap as compared to the anterior nasal spine and the size of the palatal defect that the nasoseptal flap could be used to successfully reconstruct. Composite flaps were successfully harvested in continuity with a disc of septal cartilage and contralateral mucoperichondrium, providing structural integrity to the reconstruction and the ability to anchor the flap to the native hard palate mucosa. The nasoseptal flap's maximum anterior reach was within 2.0 cm (standard deviation of 0.1 cm) from the anterior nasal spine and could reliably reconstruct palate defects of 2.5 cm or less. The nasoseptal flap provides a viable regional option for reconstructing defects of the hard palate. Prospective clinical trials are needed to investigate long-term reconstructive and functional outcomes of the composite nasoseptal flap in palatal reconstruction.

SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex.

BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown. METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions. RESULTS: We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways. CONCLUSION: Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells.

Suicide risk among cancer survivors: Head and neck versus other cancers.

BACKGROUND: Cancer survivors face psychosocial issues that increase their risk of suicide. This study examined the risk of suicide across cancer sites, with a focus on survivors of head and neck cancer (HNC). METHODS: The Surveillance, Epidemiology, and End Results 18-registry database (from 2000 to 2014) was queried for the top 20 cancer sites in the database, including HNC. The outcome of interest was suicide as a cause of death. The mortality rate from suicide was estimated for HNC sites and was compared with rates for 19 other cancer sites that were included in the study. Poisson regression was used to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for 1) HNC versus non-HNC sites (the other 19 cancer sites combined), and 2) HNC versus each individual cancer site. Models were stratified by sex, controlling for race, marital status, age, year, and stage at diagnosis. RESULTS: There were 404 suicides among 151,167 HNC survivors from 2000 to 2014, yielding a suicide rate of 63.4 suicides per 100,000 person-years. In this timeframe, there were 4493 suicides observed among 4219,097 cancer survivors in the study sample, yielding an incidence rate of 23.6 suicides per 100,000 person-years. Compared with survivors of other cancers, survivors of HNC were almost 2 times more likely to die from suicide (aRR, 1.97; 95% CI, 1.77-2.19). There was a 27% increase in the risk of suicide among HNC survivors during the period from 2010 to 2014 (aRR, 1.27; 95% CI, 1.16-1.38) compared with the period from 2000 to 2004. CONCLUSIONS: Although survival rates in cancer have improved because of improved treatments, the risk of death by suicide remains a problem for cancer survivors, particularly those with HNC.

Prevalence and sociodemographic factors associated with depression among hospitalized patients with head and neck cancer-Results from a national study.

OBJECTIVE: Depression is a significant problem for patients with head and neck cancer (HNC). This study explored the prevalence of and sociodemographic and clinical factors associated with depression, among patients with HNC. METHODS: We performed a retrospective analysis of 71 541 cases of HNC using a national dataset, the Nationwide Inpatient Sample, from 2008 to 2013. Weighted, multivariate logistic regression analysis estimated association between sociodemographic/clinical factors and tumor anatomical site with diagnosis of a major depressive disorder. RESULTS: Overall prevalence of major depressive disorder in HNC was 9.3%; highest prevalence was found in patients with laryngeal cancer (28.5%). Compared with laryngeal cancer, there were lower odds of depression among patients with oral cavity cancer (adjusted odds ratio [aOR] = 0.90; 95% CI, 0.84-0.97) and other anatomic sites (aOR = 0.87; 95% CI, 0.81-0.94), except oropharyngeal cancer (aOR = 1.00; 95% CI, 0.93-1.08). For every unit increase in comorbidities, odds of depression increased by 20% (aOR = 1.20; 95% CI, 1.19-1.23). Sociodemographic factors associated with increased odds of depression included being female (aOR = 1.77; 95% CI, 1.68-1.87), white (aOR = 1.75; 95% CI, 1.59-1.92), and having Medicaid (aOR = 1.09; 95% CI, 1.01-1.19) or Medicare insurance (aOR = 1.19; 95% CI, 1.10-1.27). CONCLUSIONS: Depression odds vary depending on HNC anatomic site, and one in four patients with laryngeal cancer may be depressed. Since depression is prevalent in this survivor cohort, it is important that psychosocial assessment and intervention are integrated into mainstream clinical care for patients with HNC.

Preoperative laboratory data are associated with complications and surgical site infection in composite head and neck surgical resections.

OBJECTIVES: 1) Describe normal/abnormal preoperative laboratory testing incidence in head and neck (H&N) composite resections and 2) determine complication, surgical site infection (SSI), and transfusion predictors by laboratory test. METHODS: The 2006 to 2013 NSQIP databases were queried for H&N composite resections. Laboratory data was categorized within, under, or above the normal reference range according to NSQIP definitions. Overall complications and SSI were analyzed with multivariable logistic regression analysis. RESULTS: From 2006 to 2013, there were 1193H&N composite resections, of which 1135 (95.1%) underwent ≥1 preoperative laboratory test. Complete blood counts were obtained in 92.3%, basic metabolic panels in 90.7%, coagulation studies in 56.2%, and liver function tests (LFTs) in 52.6%. Low sodium was found in 11.5%, increasing complication odds by 2.30 (p = 0.005). High AST comprised 10.0% and increased complication odds (OR = 2.93, p = 0.012). Additionally, 9.2% had a high white blood cell (WBC) count and 3.5% had high platelets, increasing complications by 1.92 (p = 0.030) and 3.13 (p = 0.015), respectively. BUN, creatinine, total bilirubin, albumin, alkaline phosphatase, INR, PT, and aPTT abnormal values did not affect postoperative complications. Increased SSI odds were appreciated with low sodium (OR: 2.83, p = 0.002), high AST (OR: 6.85, p < 0.001), and high alkaline phosphatase (OR: 5.46, p = 0.007). Importantly, INR had no effect on transfusion rates. High PT, aPTT, or low platelets did not change transfusion odds. CONCLUSION: Inflammatory markers are associated with complications but not SSI. High LFTs and low sodium are associated with complications and SSI. Coagulopathies did not increase transfusion rates. These findings identify laboratory studies to focus on during H&N resection preoperative assessments.

Salvage of recurrence after surgery and adjuvant therapy: A systematic review.

PURPOSE: To determine the oncologic and functional outcomes of patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma after initial management with surgery and adjuvant therapy. DATA SOURCES: Ovid Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov. REVIEW METHODS: A structured search was performed of the literature to identify studies that included patients undergoing surgical salvage for local, regional, or locoregional recurrent head and neck squamous cell carcinoma without known distant metastases who had been treated with initial surgery and post-operative adjuvant radio- or chemoradiotherapy. Studies were excluded if they did not report at least 1-year survival estimates, included patients who underwent primary non-surgical management, or included those treated with non-surgical salvage therapies or supportive care alone. RESULTS: The search strategy yielded 3746 abstracts. After applying exclusion and inclusion criteria, 126 full-texts were reviewed and six studies were included with a total of 222 patients. All studies were retrospective in design and included diverse disease subsites and stages. Complications and functional outcomes were inconsistently reported. Five-year survival estimates ranged between 10% and 40% between studies. CONCLUSIONS: Patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma after initial surgery and adjuvant therapy may have a particularly poor prognosis. Future studies are needed to determine functional and quality of life outcomes in this patient population and to identify specific prognostic factors for re-recurrence and survival.