Faculty Bibliography

OBJECTIVE: To evaluate quality of life issues in patients with laryngeal cancer after treatment with either chemoradiation or total laryngectomy and radiation therapy. METHODS: Forty-nine patients with a history of stage II-IV laryngeal squamous cell carcinoma treated primarily with either chemoradiation or by total laryngectomy with postoperative radiation completed the University of Washington Quality of Life instrument, version 4. Patients were identified on a volunteer basis in an academic university head and neck clinic setting. Each patient completed the above instrument, and statistical analysis was performed by Wilcoxon and chi 2 tests. RESULTS: Instruments were completed by all 49 patients: 15 patients who underwent primary chemoradiation and 34 patients who underwent a total laryngectomy followed by radiation. Domains reported in both treatment groups without significant differences were appearance, activity, recreation, moods, taste, saliva, anxiety, and general questions. However, there were significant differences between the 2 groups in the domains of pain, swallowing, chewing, speech, and shoulder function. The laryngectomy patients reported greater impairment of speech (P = 0.001), and shoulder function (P = 0.018), whereas the chemoradiation patients suffered from greater pain, difficulty swallowing (P = 0.061), and problems chewing (P = 0.027). CONCLUSIONS: Most patients with laryngeal cancer, whether treated primarily with chemoradiation or total laryngectomy, reported excellent functional outcomes and health-related quality of life. Pain, swallowing, chewing, saliva, and shoulder function were recorded as significant factors affecting their daily quality of life

OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCCA) has declined in the United States since the late 1970s. During this time, substantial immigration from other countries has occurred, and the average lifespan has increased. We tested the hypothesis that these trends have altered the HNSCCA patient population. STUDY DESIGN: Retrospective analysis was made of population-based data from the SEER database, a national registry capturing roughly 10% of all U.S. cancer diagnoses. METHODS: We examined all unique diagnoses of HNSCCA in the database from 1976 to 1999 and determined the breakdown of cases by age, sex, and race. RESULTS: The absolute number of new HNSCCA diagnoses per year declined overall by 5% during the time period of the study, whereas new diagnoses in patients older than 74 years of age increased by more than 20%. The rate of HNSCCA per 100,000 person-years in elderly women did not change, and the rate in elderly men decreased, indicating that the observed increase in cases is explained by a growing population of elderly persons at risk. An increase in the absolute number of cases, but not the incidence rate, was also seen among persons younger than 50 years of age. Although both the absolute number of new cases and the incidence rates of HNSCCA in white male patients declined substantially, the percentage of HNSCCA patients classified as minorities increased from 14.5% to more than 20% of all cases. During the time period of the study, the overall number of HNSCCA cases in nonwhite and Hispanic patients increased by 36%. CONCLUSION: Increasing numbers of elderly and minority patients with HNSCCA are likely to alter patterns of disease and utilization of health care resources

We applied a robust combinatorial (multi-test) approach to microarray data to identify genes consistently up- or down-regulated in head and neck squamous cell carcinoma (HNSCC). RNA was extracted from 22 paired samples of HNSCC and normal tissue from the same donors and hybridized to the Affymetrix U95A chip. Forty-two differentially expressed probe sets (representing 38 genes and one expressed sequence tag) satisfied all statistical tests of significance and were selected for further validation. Selected probe sets were validated by hierarchical clustering, multiple probe set concordance, and target-subunit agreement. In addition, real-time PCR analysis of 8 representative (randomly selected from 38) genes performed on both microarray-tested and independently obtained samples correlated well with the microarray data. The genes identified and validated by this method were in comparatively good agreement with other rigorous HNSCC microarray studies. From this study, we conclude that combinatorial analysis of microarray data is a promising technique for identifying differentially expressed genes with few false positives

BACKGROUND: Distraction osteogenesis is an established technique for the lengthening of long bones and correction of selected craniofacial deformities. Regenerate osteoid bone matrix formed during the distraction phase is malleable and can recreate the three-dimensional form of native bones. Animal experiments and early clinical experience have confirmed that distraction osteogenesis can be used for the reconstruction of segmental bony defects. Herein we discuss the principles of distraction osteogenesis in reference to reconstruction of segmental bony defects and report its clinical application of the mandible continuity defects. PATIENTS AND METHODS: Four patients (age, 7-83 years) with critical segmental mandibular defects (range, 3.5 cm-6.5 cm), resulting from ablative oncologic head and neck surgery underwent primary mandibular reconstruction by transport distraction osteogenesis. Two defects were at the angle and body region, one at the body, and the other at the parasymphysis and body region. Synthes Titanium Multi-vector and Leibinger Multi-guide distractors in bifocal (n = 2) and trifocal (n = 2) architecture were used after the stabilization of the segmental continuity defect using a defect-bridging mandibular reconstruction plate. Osteodistraction was carried out at a rate of 1 mm per day, with once or twice a day rhythm, after a 1-week latency period. The consolidation period was equal to the period of distraction. RESULTS: All patients tolerated the distraction procedure. Satisfactory bone formation was observed in two patients, and partial bone formation was seen in one patient. Treatment failure was encountered in one patient who had a second oral cavity primary tumor observed during the consolidation period, requiring interruption of the treatment sequence. CONCLUSIONS: Mandibular reconstruction with distraction osteogenesis is a potentially useful technique in selected patients with segmental mandibular continuity defects after ablative head and neck cancer surgery

BACKGROUND: The effectiveness of chemotherapeutic agents is proportional to the dose of the agents at their targets; however, the dose is limited by systemic toxicity. Attempts have been made to improve therapeutic effectiveness by increasing maximum tolerated dose (MTD) of chemotherapeutic agents using various local and regional drug delivery systems. Herein we report the use of an injectable biodegradable polymer to deliver cisplatin for intratumoral treatment of human head and neck squamous cell carcinoma (HNSCC) in a chimeric mouse model. The objectives of this research project were (1) to determine the release kinetics of cisplatin from the polymer delivery system, (2) to identify the MTD of polymer-delivered cisplatin, and (3) to evaluate its therapeutic efficacy. METHODS: To determine the in vivo release kinetics, cisplatin-loaded polymer was injected subcutaneously into rats. Implants were removed and analyzed for remaining cisplatin by a high-performance liquid chromatography technique. Sera from these rats were assayed for platinum by atomic absorption spectrophotometry. For MTD determination, SCID mice were engrafted subcutaneously with fresh biopsy specimens of HNSCC. Various doses of free or polymer-loaded cisplatin were injected intratumorally. MTD was estimated based on the threshold at which all mice survived. The antitumor efficacy of free and polymer-loaded cisplatin at their respective MTD was assayed on the same chimeric mouse model. RESULTS: The polymer delivery system released 80% of the loaded cisplatin in vivo over a 7-day period. The polymer-delivered cisplatin exhibited higher MTD (36 mg/kg) than free cisplatin (18 mg/kg) and had a statistically significant tumor suppression effect compared with free cisplatin when used at their respective MTD. CONCLUSIONS: The polymer delivery system can sustain cisplatin release for a period of 7 days. It can increase MTD and potentially enhance the antitumor efficacy of cisplatin against human head and neck cancers