Targeted multifidus muscle activation reduces fibrosis of multifidus muscle following intervertebral disc injury.

PURPOSE: Aerobic exercise produces beneficial outcomes in patients with low back pain and partially attenuates the fibrotic changes to the multifidus in a model of intervertebral disc (IVD) degeneration. More targeted exercise might be required to fully attenuate these fibrotic alterations. This study aimed to investigate whether activation of the multifidus induced by neurostimulation could reduce fibrosis of the multifidus in a model of IVD degeneration in sheep. METHODS: IVD degeneration was induced in 18 merino sheep via a partial thickness unilateral annulus fibrosus lesion to the L1/2 and L3/4 IVDs. All sheep received an implantable neurostimulation device that provides stimulation of the L2 medial branch of the dorsal ramus. Three months after surgery, the animals were assigned to Injury or Activated groups. Activated animals received neurostimulation and the Injury group received no stimulation. Six months after surgery, the multifidus was harvested at L2 and L4. Van Gieson's, Sirius Red and immunofluorescence staining for Collagen-I and -III and quantitative PCR was used to examine fibrosis. Muscle harvested from a previous study without IVD injury was used as a control. RESULTS: Neurostimulation of the multifidus attenuated IVD degeneration dependent increases in the connective tissue, including Collagen-I but not Collagen-III, compared to the Injury group at L4. No measures of the multifidus muscle at L2, which received no stimulation, differed between the Injury and Activated groups. CONCLUSIONS: These data reveal that targeted activation of the multifidus muscle attenuates IVD degeneration dependent fibrotic alterations to the multifidus.

Reference interval for the C-ACT activated clotting time test in healthy dogs using a water bath and manual assessment of clot formation.

AIMS: To establish a reference range for the canine C-ACT activated clotting time (ACT) test using a water bath and visual clot assessment technique. METHODS: Healthy, privately owned dogs (n = 48) were prospectively recruited to the study. Blood samples were collected via direct jugular venipuncture for complete blood count, serum biochemistry analysis and measurement of prothrombin time (PT) and activated partial thromboplastin time (aPTT). Five animals with major abnormalities or who became agitated during phlebotomy were excluded. For the 43 remaining animals, 2 mL of blood was collected via the cephalic vein and added directly to a C-ACT tube that was shaken vigorously before being placed in a water bath at 37°C. Tubes were visually assessed for clot formation and C-ACT was recorded in seconds when the magnet within the tube lodged in the clot. RESULTS: The nonparametric reference interval (capturing the central 95% of the data) was 50-80 seconds, with a 90% CI for the lower limit of 50-55 seconds and a 90% CI for the upper limit of 75-80 seconds. The C-ACT ACT test had a positive correlation with aPTT (0.42; 95% CI = 0.13-0.64). There was no evidence of a correlation between C-ACT ACT and age, weight, PT, haematocrit, white blood cell count, platelet count or total protein. CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study suggest that the normal reference interval for ACT in dogs using C-ACT tubes in a 37°C water bath is 50-80 seconds. Care should be taken extrapolating the results of this study to the general population, as the smaller study design had less control for confounders than a larger study. However, when using the described analytical methods, C-ACT tube ACT test results >80 seconds should be considered prolonged in dogs and should prompt further investigation.

Distribution of MLH1 foci in horse male synaptonemal complex.

Advances in molecular cytogenetics have provided the opportunity to study events during prophase I of meiosis. Immunofluorescent localization of different meiotic protein components were used to characterize the early stages of the first meiotic division in horse spermatocytes. The frequency and distribution of recombination events during prophase I were investigated using the mutL homolog 1 (MLH1) protein that is known to be associated with these events. The frequency and distribution of MLH1 foci were investigated in pachytene nuclei of 6 fertile stallions, and the average relative synaptonemal complex length was found to be highly correlated with the average number of MLH1 foci. The frequency and distribution of MLH1 foci were found to closely correspond to the frequency and distribution of chiasmata on metaphase I chromosomes, and genetic length, calculated from MLH1 foci data, for the whole genome was 2,505.5 cM.

Perceived social support as a predictor of disease-specific quality of life in head-and-neck cancer patients.

BACKGROUND: Treatment for head-and-neck cancer (HNC) can lead to severe decrements in disease-specific quality of life (DSQOL) due to disfigurement and disability in speech, eating, and/or breathing. Psychosocial factors such as social support may explain individual variance in DSQOL outcomes. OBJECTIVE: The researchers sought to evaluate changes in perceived availability of social support from pretreatment to posttreatment and to determine whether decreases in perceived social support predicted poorer posttreatment DSQOL among HNC patients, controlling for disease- and treatment-related factors. METHODS: Participants (n = 32) were newly diagnosed with HNC and were awaiting surgery and/or radiation treatment. Measures included the ENRICHD Social Support instrument (ESSI) to assess perceived social support and the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) to assess DSQOL. Paired-samples t-tests and hierarchical regression analyses were conducted to determine relationships between pretreatment and posttreatment perceived social support and DSQOL. RESULTS: Perceived social support decreased significantly from pre- to posttreatment (F[31] = -2.71, P < .01). After adjusting for relevant covariates and pretreatment DSQOL, change in perceived social support remained a significant predictor of posttreatment DSQOL (ß = .47, P < .01). LIMITATIONS: This study included a relatively small sample of HNC patients, which limited power to evaluate mechanisms of observed relationships. CONCLUSIONS: Increased social isolation may be a risk factor for poorer physical recovery from, or adjustment to, treatment-related side effects. Social support may be an important target for psychosocial interventions for patients who face challenging treatment side effects.

Green Salad Intake Is Associated with Improved Oral Cancer Survival and Lower Soluble CD44 Levels.

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p < 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of "salad or other vegetables" had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients.

Disparities in Head and Neck Cancer: A Case for Chemoprevention with Vitamin D.

Blacks experience disproportionate head and neck cancer (HNC) recurrence and mortality compared to Whites. Overall, vitamin D status is inversely associated to HNC pointing to a potential protective linkage. Although hypovitaminosis D in Blacks is well documented it has not been investigated in Black HNC patients. Thus, we conducted a prospective pilot study accessing vitamin D status in newly diagnosed HNC patients stratified by race and conducted in vitro studies to investigate mechanisms associated with potential cancer inhibitory effects of vitamin D. Outcome measures included circulating levels of vitamin D, related nutrients, and risk factor characterization as well as dietary and supplemental estimates. Vitamin D-based in vitro assays utilized proteome and microRNA (miR) profiling. Nineteen patients were enrolled, mean circulating vitamin D levels were significantly reduced in Black compared to White HNC patients, 27.3 and 20.0 ng/mL, respectively. Whites also supplemented vitamin D more frequently than Blacks who had non-significantly higher vitamin D from dietary sources. Vitamin D treatment of HNC cell lines revealed five significantly altered miRs regulating genes targeting multiple pathways in cancer based on enrichment analysis (i.e., negative regulation of cell proliferation, angiogenesis, chemokine, MAPK, and WNT signaling). Vitamin D further altered proteins involved in cancer progression, metastasis and survival supporting a potential role for vitamin D in targeted cancer prevention.

Ethical surgical triage of patients with head and neck cancer during the COVID-19 pandemic.

BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID-19 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low-grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty-five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID-19 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.

Impact of hospital volume on surgical outcome for head and neck cancer.

The objective of this study was to define the prognostic significance of surgical center case volume on outcome for head and neck cancer (HNC). Florida cancer registry and inpatient hospital data were queried for HNC diagnosed from 1998 to 2002. Of the 11,160 operative cases of HNC identified, 35.3% were treated at low-volume centers (LVCs), 32.7% in intermediate-volume centers (IVC), and 32.1% at high-volume centers (HVC). A larger proportion of high-grade tumors (27.9%) and lesions over 30 mm (39.7%) were resected at HVC (p < 0.001). Median survival was 61 months for HVC, 52 months for IVC, and 47 months for LVC (p < 0.001). Univariate analysis demonstrated significantly improved survival at HVC for low-, medium-, and high-grade tumors, small tumors (<30 mm), and for cancers of the parotid, larynx, and pharynx. On multivariate analysis, corrected for patient comorbidities, treatment at a HVC was a significant independent predictor of improved survival (HR = 1.25, p = 0.001). We conclude that HNC patients treated at HVC have significantly better long-term survival and cure rates. Where possible, patients with large (>30 mm), high-grade or parotid, larynx, and pharynx tumors should be evaluated and offered care at a high-volume center.

Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.

BACKGROUND: There is no information directly comparing midazolam with guaifenesin when used in combination with an alpha-2 agonist and ketamine to maintain anaesthesia via i.v. infusion in horses. OBJECTIVES: To compare ketamine-medetomidine-guaifenesin with ketamine-medetomidine-midazolam for total intravenous anaesthesia (TIVA) in young horses anaesthetised for computerised tomography. STUDY DESIGN: Prospective, randomised, blinded, crossover trial. METHODS: Fourteen weanlings received medetomidine 7 µg/kg bwt i.v. and anaesthesia was induced with ketamine 2.2 mg/kg bwt i.v. On two separate occasions horses each received infusions of ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, guaifenesin 100 mg/kg bwt/h (KMG) or ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, midazolam 0.1 mg/kg bwt/h (KMM) for 50 min. Cardiorespiratory variables and anaesthetic depth were assessed every 5-10 min. Recovery times after the infusions ceased were recorded and recovery quality was assessed using a composite score system (CSS), simple descriptive scale (SDS) and visual analogue scale (VAS). Multivariable models were used to generate mean recovery scores for each treatment and each recovery score system and provide P-values comparing treatment groups. RESULTS: Anaesthesia was uneventful with no difference in additional anaesthetic requirements and little clinically relevant differences in cardiopulmonary variables between groups. All horses recovered without incident with no significant difference in recovery times. Quality of the anaesthetic recovery was significantly better for the KMM group compared with the KMG group using the CSS (P<0.001), SDS (P<0.001) and VAS (P<0.001). MAIN LIMITATIONS: No surgical stimulus was applied and study animals may not represent general horse population. CONCLUSION: Midazolam is a suitable alternative to guaifenesin when co-infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. Both infusions produce a clinically comparable quality of anaesthesia; however, recovery from anaesthesia is of a better quality following an infusion of ketamine-medetomidine-midazolam.

Surface modification of bulk titanium substrates for biomedical applications via low-temperature microwave hydrothermal oxidation.

Micro-to-nanoscale surface topographies of orthopaedic and dental implants can affect fluid wetting and biological response. Nanoscale features can be superimposed on microscale roughness of titanium (Ti) surfaces at high temperatures, resulting in increased osteoblast differentiation. However, high temperatures can compromise mechanical properties of the bulk material. Here, we have developed a novel low-temperature microwave hydrothermal (MWHT) oxidation process for nanomodification of microrough (SLA) Ti surfaces. Nanoscale protuberances (20 -100 nm average diameter) were generated on SLA surfaces via MWHT treatment at 200°C in H2 O, or in aqueous solutions of H2 O2 or NH4 OH, for times ranging from 1 to 40 h. The size, shape, and crystalline content of the nanoprotuberances varied with the solution used and treatment time. The hydrophilicity of all MWHT-modified surfaces was dramatically enhanced. MG63 and normal human osteoblasts (NHOsts) were cultured on MWHT-treated SLA surfaces. While most responses to MWHT-modified surfaces were comparable to those seen on SLA controls, the MWHT-generated nanotopography reduced osteocalcin production by NHOst cells, suggesting that specific nanotopographic characteristics differentially mediate osteoblast phenotypic expression. MWHT processing provides a scalable, low-temperature route for tailoring nanoscale topographies on microroughened titanium implant surfaces with significantly enhanced wetting by water, without degrading the microscale surface structure of such implants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 782-796, 2018.

Soluble CD44 is a potential marker for the early detection of head and neck cancer.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is a devastating and deadly disease, largely because it is diagnosed in late stage. Cure rates, currently at 50%, could increase to >80% with early detection. In this study, we evaluate soluble CD44 (solCD44) as an early detection tool for HNSCC by determining whether it reliably distinguishes HNSCC from benign disease of the upper aerodigestive tract. METHODS: We carried out the solCD44 ELISA on oral rinses from 102 patients with HNSCC and 69 control patients with benign diseases of upper aerodigestive tract to determine the sensitivity and specificity of the test for differentiating HNSCC from benign disease. Furthermore, we did a pilot study using methylation-specific PCR primers on oral rinses from 11 HNSCC patients with low solCD44 levels and 10 benign disease controls. RESULTS: Mean salivary solCD44 levels were 24.4 +/- 32.0 ng/mL for HNSCC patients (range, 0.99-201 ng/mL) and 9.9 +/- 16.1 ng/mL (range, 0.73-124 ng/mL) for the patients with benign disease (P < 0.0001). Depending on cutoff point and HNSCC site, sensitivity ranged from 62% to 70% and specificity ranged from 75% to 88%. Nine of 11 HNSCC and 0 of 10 controls with low solCD44 levels showed hypermethylation of the CD44 promoter. CONCLUSIONS: SolCD44 is elevated in the majority of HNSCC and distinguishes cancer from benign disease with high specificity. Whereas the solCD44 test lacks sensitivity by itself, methylation status of the CD44 gene seems to complement the solCD44 test. Our pilot data indicate that, together, these markers will detect HNSCC with very high sensitivity and specificity.

Tunable multimodal adhesion of 3D, nanocrystalline CoFe2O4 pollen replicas.

3D replicas of sunflower pollen microparticles, comprised of a multicomponent magnetic spinel ferrite (CoFe2O4) with tailorable adhesive properties, have been synthesized for the first time via a conformal layer-by-layer (LbL) surface sol-gel (SSG) deposition process followed by organic pyrolysis and oxide compound formation at a peak temperature of 600 °C-900 °C. These high-fidelity ferrite pollen replicas exhibited multimodal (van der Waals, vdW, and magnetic) adhesion that could be tuned via control of the CoFe2O4 nanoparticle and crystal sizes. The CoFe2O4 pollen replicas exhibited a non-monotonic change in short-range (~10 nm) vdW adhesion with an increase in the peak firing temperature, which was consistent with the counteracting effects of particle coarsening on the size and number of nanoparticles present on the sharp tips of the echini (spines) on the pollen replica surfaces. The longer-range (up to ~1 mm) magnetic force of adhesion increased monotonically with an increase in firing temperature, which was consistent with the observed increases in the values of the saturation and remanent magnetization of CoFe2O4 with an increase in average nanocrystal size. By adjusting the nanocrystal/nanoparticle sizes of the CoFe2O4 pollen replicas, the total force of adhesion (vdW + magnetic) to a magnetic substrate could be increased by a factor of ~3 relative to native pollen grains.

Characterization of CD44v3-containing isoforms in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease that is only cured 50% of the time. A better understanding of the molecular mechanisms involved in HNSCC progression may lead to earlier detection and improved cure rates. CD44 is a ubiquitous transmembrane glycoprotein comprising a family of alternatively spliced isoforms involved in cell migration and cell proliferation. CD44 isoforms containing the variant 3 (v3) exon include a growth factor binding site and may be involved in tumor progression. To characterize CD44v3-containing isoforms expression in HNSCC we purified RNA from four HNSCC cell lines and performed RT-PCR using junction primer strategies followed by gel elecrophoresis. Cloning and sequencing of HNSCC cell line PCR products revealed two isoforms. One of these, CD44v3-10, has been previously described. The other isoform, CD44v3, has not been characterized in HNSCC tissues. To further study this isoform, we purified RNA from 19 HNSCC tissues, 7 normal margin tissues and 5 true normal tissues. Following reverse-transcription, we performed quantitative PCR using junction primers specific for CD44v3. Results show that HNSCC tumor tissues expressed mean CD44v3 levels that were elevated 4.5 times more than true normal tissues (p < 0.01). Mean CD44v3 values for HNSCC tumors were 0.43 +/- 0.44 while mean levels for true normal tissues were 0.10 +/- 0.11. Levels in tumor tissue did not vary significantly with tumor characteristics such as site, stage, prior treatment, or nodal status. In addition, to characterize the role of this molecule plays in tumor progression, we overexpressed CD44v3 in a HNSCC cell line. Our results indicate that although higher levels of CD44v3 did not affect the rate of proliferation, a significant increase in migration was observed. CD44v3 may provide a target for future diagnostic and therapeutic interventions for HNSCC.

Randomized trial of supplemental beta-carotene to prevent second head and neck cancer.

Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans. The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were assigned randomly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences. After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta-carotene had no significant effect on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were statistically significant, the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk. These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans, in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology, and in animal carcinogenicity studies, in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis, with some suggestions of tumor-promoting effects in respiratory tract/lung. If our results are replicated by other ongoing/completed trials, this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site (head and neck) versus another (lung).

Risk Stratification System for Oral Cancer Screening.

Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in incidence. Worldwide 5-year survival is only 50% due to delayed intervention with more than half of the diagnoses at stage III and IV, whereas earlier detection (stage I and II) yields survival rates up to 80% to 90%. Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels may facilitate oral cancer risk assessment and early intervention. This study used a hospital-based design with 150 cases and 150 frequency-matched controls to determine whether CD44 and total protein levels in oral rinses were associated with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol use, and socioeconomic status (SES). High-risk subjects receiving oral cancer prevention interventions as part of a community-based program (n = 150) were followed over 1 year to determine marker specificity and variation. CD44 ≥5.33 ng/mL was highly associated with case status [adjusted OR 14.489; 95% confidence interval (CI), 5.973-35.145; P < .0001, vs. reference group CD44 <2.22 ng/mL and protein <1.23 mg/mL]. Total protein aided prediction above CD44 alone. Sensitivity and specificity in the frequency-matched study was 80% and 48.7%, respectively. However, controls were not representative of the target screening population due, in part, to a high rate of prior cancer. In contrast, specificity in the high-risk community was 74% and reached 95% after annual retesting. Simple and inexpensive salivary CD44 and total protein measurements may help identify individuals at heightened risk for oral cancer from the millions who partake in risky behaviors. Cancer Prev Res; 9(6); 445-55. ©2016 AACR.

Effect of actionable somatic mutations on racial/ethnic disparities in head and neck cancer prognosis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. METHODS: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%). RESULTS: Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage. CONCLUSION: We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016.

How Do head and neck cancer patients prioritize treatment outcomes before initiating treatment?

PURPOSE: To determine, pretreatment, how head and neck cancer (HNC) patients prioritize potential treatment effects in relationship to each other and to survival and to ascertain whether patients' preferences are related to demographic or disease characteristics, performance status, or quality of life (QOL). PATIENTS AND METHODS: One hundred thirty-one patients were assessed pretreatment using standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck) and performance (Performance Status Scale for Head and Neck Cancer). Patients were also asked to rank a series of 12 potential HNC treatment effects. RESULTS: Being cured was ranked top priority by 75% of patients; another 18% ranked it second or third. Living as long as possible and having no pain were placed in the top three by 56% and 35% of patients, respectively. Items that were ranked in the top three by 10% to 24% of patients included those related to energy, swallowing, voice, and appearance. Items related to chewing, being understood, tasting, and dry mouth were placed in the top three by less than 10% of patients. Excluding the top three rankings, there was considerable variability in ratings. Rankings were generally unrelated to patient or disease characteristics, with the exception that cure and living were of slightly lower priority and pain of higher priority to older patients compared with younger patients. CONCLUSION: The data suggest that, at least pretreatment, survival is of primary importance to patients, supporting the development of aggressive treatment strategies. In addition, results highlight individual variability and warn against making assumptions about patients' attitudes vis-à-vis potential outcomes. Whether patients' priorities will change as they experience late effects is currently under investigation.

Salivary soluble CD44: a potential molecular marker for head and neck cancer.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease which is cured only 50% of the time. If diagnosed early, survival rates could reach 80%, but there is currently no practical method for early detection. CD44 comprises a family of isoforms that, in certain tumors, are alternatively spliced and overexpressed in tissues and circulation. Here we examine salivary soluble CD44 (solCD44) expression in HNSCC patients and normal controls to determine its potential as a screening tool. METHOD: We did a solCD44 ELISA on saliva from 26 HNSCC patients, 10 normal volunteers, conditioned media (CM) of 4 HNSCC cell lines, and 1 CD44-negative cell line (COS-7). Western blot was done on CM from 2 HNSCC cell lines (UMSS11B and FaDu), COS-7, 3 HNSCC, and 2 normal saliva specimens to verify ELISA antibody specificity. SolCD44 levels were significantly elevated in HNSCC patients compared with normal controls (7.85 ng/mL for HNSCC patients and 1.09 ng/mL for normal controls, P < 0.001). RESULTS: The test detected 79% of mucosally invasive HNSCC using preliminary cutoff points. SolCD44 levels did not vary significantly with tumor size, stage, recurrence, history of radiation treatment, or tobacco and alcohol risk factors. A 65 to 75 kDa band, corresponding to solCD44, was detected in all of the HNSCC cell line CM and saliva whereas normal samples showed a fainter band or were undetectable. CONCLUSION: In this preliminary analysis, the salivary solCD44 ELISA seems to effectively detect HNSCC at all stages. Further study is indicated because early detection is clearly important in this disease.

Primary carcinosarcoma of the helix of the ear.

We report our histologic and immunohistochemical findings in a rare case of cutaneous carcinosarcoma involving the helix of the ear. The tumor exhibited cellular features of both basal cell and squamous cell carcinoma and a malignant mesenchymal component that was consistent with malignant fibrous histiocytoma. The epithelial component exhibited a positive immunohistochemical reaction to cytokeratin and a negative reaction to vimentin, whereas the mesenchymal component showed a positive immunohistochemical reaction to vimentin and a negative reaction to cytokeratin. To the best of our knowledge, this is only the third reported case of a carcinosarcoma of the ear and the second case in which it developed on the helix.