Ultrasound-Guided Transcutaneous Needle Biopsy of the Base of the Tongue and Floor of the Mouth From a Submental Approach.

Limited data exist regarding the feasibility of ultrasound-guided transcutaneous biopsy of the base of the tongue and floor of the mouth. This retrospective study reviewed 8 cases with lesions in the base of the tongue or floor of the mouth that were biopsied by fine-needle aspiration. Core biopsy was also needed in 1 case. All biopsies were technically successful, and all yielded squamous cell carcinoma. One biopsy yielded a false-positive result, as subsequent resection yielded high-grade dysplasia with no invasion. The other biopsy results were considered true-positive based on subsequent pathologic examinations (2 cases) or clinical/imaging follow-up (5 cases). There were no significant complications associated with the biopsies.

Trends and factors associated with receipt of human papillomavirus (HPV) vaccine in private, public, and alternative settings in the United States.

BACKGROUND: One of the goals of the President's Cancer Panel was to maximize access to human papillomavirus (HPV) vaccination through expansion of alternative settings for receiving the vaccine, such as in public health settings, schools, and pharmacies. METHODS: In a cross-sectional analysis, we utilized the National Immunization Survey-Teen data from 2014 to 2020 (n = 74,645) to describe trends and factors associated with HPV vaccine uptake in private, public, and alternative settings. We calculated annual percent change (APC) between 2014 and 2020, estimating rate of HPV vaccine uptake across settings. Using multinomial logistic regression, we estimated the odds of receipt of HPV vaccine in public health settings and other alternative settings compared to private healthcare settings, adjusting for sociodemographic covariates. RESULTS: We found a 5 % annual increase in the use of private facilities between 2014-2018 (APC = 5.3; 95 % CI 3.4, 7.1), and almost 7 % between 2018-2020 (APC = 6.7; 95 % CI 1.4, 12.3). Adjusted multinomial logistic regression analyses found that odds of receiving vaccinations at a public facility vs. a private facility increased almost two times for adolescents living below poverty (aOR = 1.82, 95 % CI: 1.60, 2.08) compared to above poverty. Additionally, adolescents without physician recommendations had lower odds of receiving vaccines at public versus private facilities (aOR = 1.75, 95 % CI: 1.44, 2.12). Finally, odds of receiving HPV vaccines at public facilities vs. private facilities decreased by 33 % for White adolescents (aOR = 0.67, 95 % CI: 0.57, 0.78) versus Black adolescents. CONCLUSIONS: Sociodemographic factors such as race, and socioeconomic factors such as poverty level, and receipt of physician HPV recommendations are associated with receiving the vaccine at private settings vs. public health facilities and alternative settings. This information is important in strengthening alternative settings for HPV vaccine uptake to increase access to the vaccine among disadvantaged individuals.

Salvage Surgery.

The Department of Veterans Affairs Laryngeal Cancer Study propelled the combination of chemotherapy and radiation therapy to the forefront of strategies used for the management of locally advanced laryngeal cancer. The organ preservation rate was 84%. However, over the past 30 years that these approaches have been in place, there have been concerns regarding long-term survival and high failure rates requiring salvage. Furthermore, salvage laryngectomy, if feasible when considering increased morbidity after CRT, is fraught with a higher risk of wound complications including fistula, longer hospitalization, and reduced quality of life.

Octreotide may improve pharyngocutaneous fistula healing through downregulation of cystatins: A pilot study.

Background: Pharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide. Methods: Four healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration. Results: There were 3076 human, 332 Streptococcus mitis, 102 G. haemolyans, and 42 Granulicatella adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ~300 proteins that had a p < .05 between the pre- and post-octreotide groups ~50 proteins with an FDR-corrected p < .05 between pre- and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment. Conclusion: This pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide's effects on saliva and reports of improved PCF healing.

Lateral neck dissection surgeon volume and complications in head and neck endocrine malignancy.

Background: Increased surgeon volume is associated with decreased complications for many surgeries, including thyroidectomy. We sought to use two national databases to assess for associations between surgeon volume and complications in patients undergoing lateral neck dissection for thyroid or parathyroid malignancy. Methods: Lateral neck dissections for thyroid and parathyroid cancer from the Nationwide Inpatient Sample and State Inpatient Database were analyzed. The primary outcome was any inpatient complication common to thyroidectomy, parathyroidectomy, or lateral neck dissection. The principle independent variable was surgeon volume. Multivariable analysis was then performed on this retrospective cohort study. Results: The 1,094 Nationwide Inpatient Sample discharges had a 28% (305/1,094) complication rate. After adjustment, surgeons with volumes between 3-34 neck dissections/year demonstrated a surgeon volume-complication rate association [adjusted odds ratio: 1.03; 95% confidence interval (CI): 1.01-1.05]. The 1,235 State inpatient Database discharges had a 21% (258/1,235) overall complication rate, and no association between surgeon volume and complication rates (P=0.25). Conclusions: This retrospective review of 2,329 discharges for patients undergoing lateral neck dissection for thyroid or parathyroidectomy demonstrated somewhat conflicting results. The Nationwide Inpatient Sample demonstrated increasing complication rates for increasing surgeon volume among intermediate volume surgeons, while the State Inpatient Database demonstrated no surgeon volume-complication association. Given these disparate results, and further limitations with these databases, conclusions regarding surgical volume and clinical decision making based on these data should be assessed cautiously.

Oromandibular reconstruction.

Mandibular reconstruction is often necessary due to congenital, traumatic, infectious, and following treatment for neoplasms of the region. Mandibular defects following ablative surgery for malignant tumors of the head and neck region impact both form and function and require a multidisciplinary approach to optimize functional and cosmetic outcomes. A variety of options exist for mandibular reconstruction and ranging from primary closure, allografts, and autografts, to locoregional and free tissue transfers. This article will focus upon the reconstructive and rehabilitative options for mandibular defects following treatment for head and neck tumors.

Differential Outcomes Among Survivors of Head and Neck Cancer Belonging to Racial and Ethnic Minority Groups.

Importance: Approximately 1 in 5 new patients with head and neck cancer (HNC) in the US belong to racial and ethnic minority groups, but their survival rates are worse than White individuals. However, because most studies compare Black vs White patients, little is known about survival differences among members of racial and ethnic minority groups. Objective: To describe differential survival and identify nonclinical factors associated with stage of presentation among patients with HNC belonging to racial and ethnic minority groups. Design, Setting, and Participants: This population-based retrospective cohort study used data from the 2007 to 2016 Surveillance, Epidemiology, and End Results (SEER) database and included non-Hispanic Black, Asian Pacific Islander, American Indian/Alaska Native, and Hispanic patients with HNC. The data were analyzed from December 2020 to May 2021. Main Outcomes and Measures: Outcomes were time to event measures: (HNC-specific and all-cause mortality) and stage of presentation. Covariates included nonclinical (age at diagnosis, sex, race and ethnicity, insurance status, marital status, and a composite socioeconomic status [SES]) and clinical factors (stage, cancer site, chemotherapy, radiation, and surgery). A Cox regression model was used to adjust associations of covariates with the hazard of all-cause death, and a Fine and Gray competing risks proportional hazards model was used to estimate associations of covariates with the hazard of HNC-specific death. A proportional log odds ordinal logistic regression identified which nonclinical factors were associated with stage of presentation. Results: There were 21 966 patients with HNC included in the study (mean [SD] age, 56.02 [11.16] years; 6072 women [27.6%]; 9229 [42.0%] non-Hispanic Black, 6893 [31.4%] Hispanic, 5342 [24.3%] Asian/Pacific Islander, and 502 [2.3%] American Indian/Alaska Native individuals). Black patients had highest proportion with very low SES (3482 [37.7%]) and the lowest crude 5-year overall survival (46%). After adjusting for covariates, Hispanic individuals had an 11% lower subdistribution hazard ratio (sdHR) of HNC-specific mortality (sdHR, 0.89; 95% CI, 0.83-0.95), 15% lower risk for Asian/Pacific Islander individuals (sdHR, 0.85; 95% CI, 0.78-0.93), and a trending lower risk for American Indian/Alaska Native individuals (sdHR, 0.85; 95% CI, 0.71-1.01), compared with non-Hispanic Black individuals. Race, sex, insurance, marital status, and SES were consistently associated with all-cause mortality, HNC-specific mortality, and stage of presentation, with non-Hispanic Black individuals faring worse compared with individuals of other racial and ethnic minority groups. Conclusions and Relevance: In this cohort study that included only patients with HNC who were members of racial and ethnic minority groups, Black patients had significantly worse outcomes that were not completely explained by stage of presentation. There may be unexplored multilevel factors that are associated with social determinants of health and disparities in HNC outcomes.

Nonsurgical Risk Factors Associated With Pharyngocutaneous Fistula in Patients Who Have Undergone Laryngectomy.

Importance: Pharyngocutaneous fistula (PCF) is a serious complication after total laryngectomy. Despite the well-described clinical risk factors for PCF and its association with poor quality of life, there is a paucity of data on the nonclinical factors that may be associated with this complication. Objective: To determine whether nonclinical risk factors (eg, age, sex, race and ethnicity) are associated with an increased risk of developing a PCF after total laryngectomy, and whether or not the method of reconstruction explains any differences found. Design, Setting, and Participants: This retrospective multicenter cohort study used data from a nationally validated, risk-adjusted, outcomes-based, surgical quality improvement database (the National Surgical Quality Improvement Program) to examine outcomes in patients who underwent a total laryngectomy from 2005 to 2018. The database was queried from January 1, 2005, to December 31, 2018; data analyses were performed from September 1, 2020, to March 31, 2021. Main Outcomes and Measures: The primary outcome was development of a PCF within 30 days of a total laryngectomy. Patient characteristics, including age, sex, race and ethnicity, comorbidities, and mode of reconstruction, were analyzed. Results: A cohort of 1573 adult patients (median age [IQR], 63 [56-71] years; 1280 [81.4%] men; 293 [18.6%] women; 1001 [63.6%] non-Hispanic White individuals) had undergone a total laryngectomy during the study period and were included in the analyses. The overall rate of PCF formation was 4.3% (68 of 1573 patients). Hispanic patients had the highest rate (9.5%; 9 of 95 patients) of PCF formation, which was more than twice the rate among non-Hispanic White patients (3.8%; 38 of 1001) and non-Hispanic Black patients (4.7%; 11 of 236). After adjusting for clinical and other covariates, women were 1.9 times more likely to develop a PCF compared with men (adjusted odds ratio, 1.90; 95% CI, 1.08-3.35). We also found that the odds of developing a PCF were 3-fold higher among Hispanic patients compared with non-Hispanic White patients (adjusted odds ratio, 2.96; 95% CI, 1.36-6.47). The type of reconstruction did not differ across age or race and ethnicity after controlling for clinical risk factors. Conclusions and Relevance: This multicenter cohort study found that 2 nonclinical risk factors-Hispanic ethnicity and female sex-were associated with an increased risk of PCF formation. Knowledge of these risk factors should be included in patient-physician decision-making as well as future interventions to decrease the rate of PCF formation after laryngectomy.

Surgeon Volume and Complications in Lateral Neck Dissection for Squamous Cell Carcinoma: A Multidatabase Analysis.

OBJECTIVE: To determine whether annual surgeon volume of lateral neck dissections for squamous cell carcinoma is associated with complication rates. STUDY DESIGN: Retrospective review. SETTING: Two US databases spanning 2000 to 2014. METHODS: Neck dissections for squamous cell carcinoma from the National Inpatient Sample and State Inpatient Databases were analyzed. The primary outcome was any in-hospital complication common to neck dissection. The principal independent variable was surgeon volume. A multivariable logistic generalized estimating equation with a piecewise linear spline for surgeon volume was fit to assess its association with complication. RESULTS: The National Inpatient Sample had 3517 discharges fitting criteria, a median surgeon volume of 12, and an 11.1% complication rate. A 1-unit increase in surgeon volume was associated with a 7% increase in the odds of complication when volume ranged between 4 and 19 (adjusted odds ratio [AOR], 1.07; 95% CI, 1.04-1.11) and with a 3% decrease in the odds of complication when volume ranged between 19 and 51 (AOR, 0.97; 95% CI, 0.96-0.99). The State Inpatient Databases had 2876 discharges fitting criteria, a median surgeon volume of 30, and a 13.5% complication rate. Surgeon volume was not associated with complication when <27 (AOR, 1.01; 95% CI, 0.99-1.02), but a 5-unit increase in volume was associated with a 7% decrease in the odds of complication with volume ≥27 (AOR, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS: Surgeon volume was associated with complications for most volume ranges and with lower odds of complication for high-volume surgeons.

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review.

BACKGROUND: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. METHODS: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. RESULTS: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). CONCLUSIONS: The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.

Defining cancer cachexia in head and neck squamous cell carcinoma.

PURPOSE: Cancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma (HNSCC). The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC. The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors. EXPERIMENTAL DESIGN: For the primary objective, cross-sectional data were obtained from prospectively recruited patients identified as cachexia cases and matching cachexia-free controls. For the secondary objective, a retrospective cohort design with matched controls was used. RESULTS: Clinical characteristics associated with cancer cachexia in HNSCC were T(4) status (P = 0.01), increased C-reactive protein (P = 0.01), and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 (P = 0.04). A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients (P = 0.02). Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients (P < 0.01). All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor. There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients (each P > 0.05). No tumors expressed the cachexia factor proteolysis-inducing factor. CONCLUSION: We have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC. The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state. We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia.

Comparison of animal models for head and neck cancer cachexia.

OBJECTIVES/HYPOTHESIS: Despite its negative impact on cancer patients, there are few animal models of cancer cachexia. Our hypothesis was that different human cell lines would variably induce cachexia. STUDY DESIGN: Prospective animal study. METHODS: We established two xenograft models in athymic mice and compared these with a cachexigenic cell line, the murine adenocarcinoma 16 (MAC16) cell line. Eight-week-old female, athymic mice were injected with human head and neck cell lines (JHU022, JHU012) and the MAC16 cell line. Body weight, food intake, body composition, leg weights, serum cytokines, and lipid mobilizing factor (LMF) were compared. RESULTS: Mean food intake for all groups was equivalent. Mean percent change in body weight after 18 days was 18%, 19%, 12%, and 3% for control, JHU012, JHU022, and MAC16 experimental groups, respectively. Both JHU022- and MAC16-injected mice showed wasting even when tumor burden was low. In contrast, mice injected with JHU012 developed larger tumors yet lacked evidence of cachexia. These mice demonstrated loss of lean body mass but not fat mass. Serum cytokine levels for interleukin (IL)-1 alpha and IL-1 beta were elevated in JHU022-bearing mice, whereas IL-1 alpha, IL-6, interferon (IFN)-gamma, and tumor necrosis factor alpha (TNF)-alpha were elevated in MAC16-bearing mice. LMF was present in both the JHU022 and JHU012 cell lines. CONCLUSIONS: The JHU022 cell line caused more severe cachexia than the JHU012 cells, suggesting these cell lines may be used to further study cancer cachexia. IL-1 alpha and IL-1 beta in the JHU022 model may be mediators of cachexia, whereas TNF-alpha, IFN-gamma, and IL-6 may be mediators in MAC16-induced cachexia.

The effect of altered Toll-like receptor 4 signaling on cancer cachexia.

OBJECTIVE: To determine whether mice unable to mount an intact inflammatory response because of a Toll-like receptor (TLR) pathway defect will develop less severe cancer cachexia. DESIGN: Prospective animal study. SETTING: Academic research center. SUBJECTS: Six- to eight-week-old, female C3H/HeJ mice (17-18 g) and age-, weight-, and sex-matched wild-type C3H/HeN mice, differing in that the HeJ mice have nonfunctional TLR4 due to a TLR4 double mutation (TLR4(d/d)). INTERVENTION: The mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages. MAIN OUTCOME MEASURES: Food intake, body weight, pretumor and posttumor body composition, circulating cytokines, and levels of a marker of muscle atrophy were analyzed. RESULTS: The wild-type HeN mice weighed less on average than the TLR4(d/d) mice (2.6 g vs 4.9 g) (P = .01). They consumed more food, had smaller tumors, and had less lean body mass and fat mass than the TLR4(d/d) mice. Interleukin 1beta level was significantly elevated in the tumor-bearing HeN mice (mean gain of 259 pg/mL) but not in the TLR4(d/d) mice (P = .03). Both mouse strains had evidence of muscle atrophy. CONCLUSIONS: In spite of increased food intake and smaller tumors, the wild-type HeN mice had more severe cachexia than the TLR4(d/d) mice. The impaired ability to secrete proinflammatory cytokines such as interleukin 1beta may protect these animals from developing severe cancer cachexia. This animal model represents a novel system in which the host contributions to cachexia may be further studied.

Nasopharyngeal carcinoma in young patients: a systematic review of racial demographics.

OBJECTIVES: To evaluate patients 25 years of age or younger who were treated for nasopharyngeal carcinoma. STUDY DESIGN: Retrospective review, systematic literature review. METHODS: Nasopharyngeal carcinoma (NPC) is rare in the Western world. In people younger than 30 years, it is even less common, with an incidence of 1 to 2 per million. This retrospective study was designed to analyze the outcomes of patients 25 years of age or younger who were treated for NPC at a tertiary care academic medical center. Between November 1982 and December 2004, 15 patients meeting the above criteria were treated. These patients form the basis for this report. A systematic review of all NPC trials published in the United States since 1990 was done and the results compared with those of our cohort. RESULTS: Young African Americans represented 67% of the 15 cases seen at our institution and between 55% and 67% of the patients in the United States. With a mean follow-up of 5.36 years, disease-free survival and overall survival rates were 67% and 87%, respectively. Locoregional control was excellent after treatment with cisplatin-based combination chemoradiotherapy; however, four patients (27%) developed distant metastasis. Despite this, no patients died of disease. Toxicity was significant but manageable, and retreatment met with good success. CONCLUSIONS: In patients 25 years of age or younger, NPC is more common in African Americans. This may represent a genetic and racial predisposition of this unusual disease in the United States. Late-stage presentations and distant recurrences are common. Platinum-based combination chemoradiotherapy and aggressive management of metastatic disease, however, is associated with good long-term survival. Further study of the possibly changing epidemiology and racial genetics of this unusual tumor is warranted.

Incidence and survival rates for young blacks with nasopharyngeal carcinoma in the United States.

OBJECTIVES: To compare the incidence rates of nasopharyngeal carcinoma (NPC) among US black, white, and Asian/Pacific Islander (Asian) populations, with a focus on those diagnosed before age 20 years and between ages 20 and 29 years. Our secondary objective was to determine differences in survival rates between US blacks, whites, and Asians with NPC who were younger than 30 years. DESIGN: Data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) tumor registry system were used to determine incidence and survival rates for cases of NPC diagnosed in the specified age groups between 1973 and 2002. PATIENTS: Blacks, whites, and Asians younger than 30 years with NPC. MAIN OUTCOME MEASURES: Incidence rates and 2- and 5-year survival rates. RESULTS: From 1973 to 2002, incidence rates per 1 million persons, adjusted to the 2000 standard population, for blacks, whites, and Asians younger than 20 years with NPC were 1.61 (n=43), 0.61 (n=99), and 0.95 (n=18), respectively. The incidence rate ratio of blacks to Asians younger than 20 years was 1.69 (95% confidence interval [CI], 0.96-3.12) (P=.07), while the rate ratio for blacks to whites was 2.66 (95% CI, 1.82-3.85) (P<.001). From ages 20 to 29 years, rates increased slightly in blacks (1.87) and whites (0.96), while increasing dramatically in Asians (7.18). Two- and 5-year relative survival rates in blacks younger than 30 years were 84% and 64%, respectively, with little variation between races in this age group. CONCLUSIONS: Blacks younger than 20 years have increased incidence rates of NPC relative to whites and may be the only group having a higher NPC incidence rate than Asians. Two- and 5-year survival rates of blacks, whites, and Asians younger than 30 years with NPC are similar.

Sex differences in distortion product otoacoustic emissions as a function of age in CBA mice.

Age-related hearing loss--presbycusis--is the number one communication problem of the aged. A major contributor to presbycusis is the progressive degeneration of cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions (DPOAEs) are effective in vivo, physiological measures of hearing, assessing the health and functioning of the OHCs in mammals. We and others have previously demonstrated that DPOAE amplitudes decline with age in humans and mice. The present study's objective was to measure age-related declines in the OHCs in CBA mice (slow, progressive age-related hearing loss) by comparing DPOAEs and auditory brainstem responses (ABRs) generated from females and males. Young adult (2.1-2.9 months) and middle-aged CBA (14.0-16.4 months) mice were tested, as well as old CBAs (24.3-29.0 months). DPOAE-grams were obtained with L1 = 65 and L2 = 50 dB SPL, f1/f2 = 1.25, using eight points per octave covering a frequency range from 5.6 to 44.8 kHz (geometric mean frequency). ABRs ranged from 3 to 48 kHz. Analyses revealed that DPOAE levels decreased with age for middle-aged and old male CBAs, but for female CBAs, declines did not occur until old age - after menopause. In contrast, ABR amplitudes for female and male young adult and middle-aged CBAs were the same. Female ABR thresholds were lower than males for old CBAs. In conclusion, we discovered that pre-menopausal CBA female mice have healthier OHCs relative to middle-aged males, but much of this relative advantage is lost post-menopause. Understanding sex differences in age-related sensory disorders will be quite helpful for the goals of preventing, slowing or curing sensory problems in old age for both women and men.

Liver function tests: inadequate screening modality for detection of liver metastasis in head and neck carcinoma.

OBJECTIVE: Report the prevalence and risk factors of liver metastasis in head and neck squamous cell carcinoma (HNSCC) while evaluating the utility of liver function tests (LFTs) in detection of such metastases. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Of 745 patients with newly diagnosed HNSCC (oral cavity, oropharynx, hypopharynx, larynx) treated at University of North Carolina hospitals from 1989 to 2005, 655 had sufficient data for analysis. RESULTS: Prevalence of liver metastasis was 3% (20/655) with 7 patients demonstrating early metastasis and 12 with late metastasis. Oropharyngeal and hypopharyngeal lesions constituted 65% of identified liver metastasis but only 39% of the study population. Patients with oropharyngeal lesions were most likely to develop liver metastasis (P = .047). Abnormal LFTs were seen in 26% of all patients. Overall sensitivity and specificity were 45% and 75%. Seventy-five percent of patients with liver metastasis had stage IV disease at diagnosis and were more likely to have abnormal LFTs than other stages (P = .048). In these patients, 2.2% (8/365) had liver metastases and abnormal LFTs, whereas 1.9% (7/365) had liver metastases and normal LFTs. Sensitivity for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase 0%, 10%, 20%, and 30%, respectively. Specificities ranged from 88.0% to 94.3%. Positive predictive values were poor, with the highest being 10.5%. CONCLUSIONS: Liver metastases are rare in HNSCC and often delayed in presentation. This study clearly reveals that LFTs do not reliably identify patients with liver metastasis and do not provide physicians with an adequate screening modality in this population.