Cherie-Ann O. Nathan

Molecular analysis of surgical margins in head and neck squamous cell carcinoma patients

Objectives/Hypothesis Molecular analysis of surgical margins is playing an increasingly important role in establishing surgical margins. Most markers lack the sensitivity and ease of applicability for effective clinical use. To date, the proto‐oncogene eIF4E (4E) is elevated in 100% of head and neck squamous cell carcinoma tumors and is of prognostic value in predicting recurrence. In a retrospective study, 4E overexpression in the margins appeared to be a more sensitive predictor of recurrence when compared with p53. The goal was to confirm this finding in a prospective study and also to compare the expression of matrix metalloproteinase‐9 (MMP‐9) to 4E expression in tumors and margins. Other objectives were to determine which of these markers have prognostic significance in predicting recurrence and elucidate whether there is any additional benefit to analysis of surgical margins with a combination of the three molecular markers.

Antisense RNA to eIF4E suppresses oncogenic properties of a head and neck squamous cell carcinoma cell line

Objective The translation initiation factor eIF4E is elevated in all head and neck squamous cell cancers (HNSCCs) and appears to be essential in the progression of solid tumors. Overexpression of eIF4E results in preferential upregulation of two angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF‐2). We wanted to determine whether reducing eIF4E in a HNSCC cell line could suppress its oncogenic properties and in turn decrease expression of VEGF and FGF‐2.

Expression of eIF4E During Head and Neck Tumorigenesis: Possible Role in Angiogenesis†‡

Objective: The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation. 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF‐2) by selectively enhancing their translation. 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins. Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions. Molecular events underlie the histological changes that herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis.

Reflux as a cause of tracheoesophageal puncture failure.

To evaluate the response to empiric reflux management in treatment of tracheoesophageal punctures (TEP) failures.

Molecular profiling of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) exhibits high rates of recurrence, and with few approved targeted agents, novel treatments are needed. We analyzed a molecular profiling database for the distribution of biomarkers predictive of chemotherapies and targeted agents.

A pilot study of quantitative aspiration in patients with symptoms of obstructive sleep apnea: Comparison to a historic control group

Objective: It has been shown that many healthy people aspirate secretions at night. Patients with obstructive sleep apnea (OSA) have frequent episodes of gasping at night that may predispose them to aspiration. The purpose of this study was to determine whether patients with symptoms of OSA are predisposed to pharyngeal aspiration.

Serum Biomarkers in Head and Neck Squamous Cell Cancer

IMPORTANCEnSerum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials.nnnOBJECTIVEnTo determine serum cytokine and chemokine concentrations altered in patients with HNSCC compared with healthy volunteers to identify potential biomarkers.nnnDESIGN, SETTING, AND PARTICIPANTSnA retrospective experimental laboratory study at Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport. Serum samples from 50 patients with stages II, III, and IV HNSCC and 20 healthy volunteers were available for study. Primary tumor sites represented in the patient group included the nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx.nnnINTERVENTIONSnFollowing institutional review approval and written informed consent, blood samples were drawn from patients. No intervention, to include any kind of diagnostic workup or treatment, was provided to patients during the course of this study.nnnMAIN OUTCOMES AND MEASURESnThe main outcome measures were the quantification of cytokine and chemokine concentrations in serum samples. Luminex multiplex panel technology was used for simultaneous measurement of 18 analytes, including fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, growth-related oncogene, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, inducible protein (IP)-10, soluble CD40 ligand, tumor necrosis factor, and vascular endothelial growth factor.nnnRESULTSnThe serum samples of patients with HNSCC contained lower levels of IFN-γ (mean patient serum level, 6.08 pg/mL, compared with the mean control level, 26.20 pg/mL; Pu2009=u2009.004), IL-13 (mean patient serum level, 2.85 pg/mL, compared with the control mean level, 7.23 pg/mL; Pu2009=u2009.02), and macrophage inflammatory protein-1β (MIP-1β) (mean patient serum level, 14.91 pg/mL, compared with the mean control level, 28.98 pg/mL; Pu2009=u2009.004), and elevated levels of IP-10 (mean patient serum level, 359.24 pg/mL, compared with mean control level, 216.40 pg/mL; Pu2009=u2009.04). All other markers tested were not significantly different between patients with cancer and controls.nnnCONCLUSIONS AND RELEVANCEnThis pilot study demonstrated a significant decrease in serum IFN-γ, IL-13, and MIP-1β levels and a significant elevation of serum IP-10 concentration in patients with HNSCC, irrespective of primary tumor site. If validated in larger, independent studies, these serum biomarkers may be useful in the diagnosis and treatment of HNSCC. In the future, a defined, multianalyte screening panel could facilitate early diagnosis of HNSCC, allowing for earlier treatment and thereby reducing patient mortality.

Oral dysplasia and squamous cell carcinoma: Correlation between increased expression of CD21, Epstein-Barr virus and CK19

OBJECTIVESnEpstein-Barr virus is an orally transmitted human gammaherpesvirus that infects B lymphocytes and epithelial cells. Although most primary infections are asymptomatic, long term carriage of the virus can be associated with either lymphoid or epithelial malignancies. The association of EBV with oral squamous cell carcinomas is sporadic and it is uncertain if the virus is involved in initiation of the tumor or, possibly, in its progression. Complement receptor type 2, CR2 or CD21, is a receptor for the major attachment protein of EBV, which significantly enhances epithelial cell infection, but its expression on normal tissues is restricted to tonsil and adenoid epithelium. As cells become dysplastic they are reported to express higher levels of CK19. We sought to evaluate whether CD21 and CK19 expression change as oral epithelial cells outside Waldeyers ring become dysplastic.nnnMATERIALS AND METHODSnEpithelial cells were isolated by laser capture microdissection and levels of CD21, CK19 and EBV RNA were measured by quantitative reverse transcriptase PCR.nnnRESULTSnWe report that expression of CD21 increases in frequency and intensity as oral epithelial cells become more dysplastic and that expression correlates with an increase in infection by EBV. Tumors or dysplastic lesions that carry EBV also generally express higher levels of CK19 than those that do not.nnnCONCLUSIONnThe findings suggest that dysplasia may make cells more susceptible to infection by EBV and that infection by the virus may alter the phenotype of the infected cell in a manner which could affect prognosis.

Botulinum toxin: Adjunctive treatment for posterior glottic synechiae†

Introduction: Synechiae formation of the posterior glottis can result in tracheostomy dependence secondary to airway obstruction. Stenosis is caused by total or partial fixation of the vocal folds in adduction resulting from scar contracture. The treatment poses a management dilemma because of recurrent scar formation, made worse by mobility of the vocal folds. Although various treatment options from conservative endoscopic repair to open procedures have been proposed, the results are not satisfactory and patients often require multiple procedures. Methods: We present the trial of a conservative approach that includes microscopic CO2 laser resection of the scar with concomitant botulinum toxin injection of the interarytenoid and thyroarytenoid muscles of the more mobile cord. This results in a temporary paresis of the adductor muscles and hence prevents overadduction in the posterior commissure during the postoperative healing period. Study Design: We present the surgical technique and results in three patients who underwent the procedure. Results: Treatment in all three patients was successful. Conclusions: The appropriate use of botulinum toxin may help improve the treatment outcome of posterior synechiae of the larynx without sacrificing any laryngeal components. Key Words: Larynx, stenosis, botulinum toxin.

Comorbid predictors of poor response to chemoradiotherapy for laryngeal squamous cell carcinoma.

To investigate whether a correlation exists between medical comorbidities and disease control following primary therapy of laryngeal squamous cell carcinoma.