Faculty Bibliography

Native cellular fluorescence (NCF) is being investigated as an intermediate endpoint biomarker for chemoprevention. Oral epithelial cells were cultured under three conditions to identify a spectral pattern for epithelial differentiation: cells maintained in serum-free keratinocyte growth medium were the least differentiated (KGM cells); cells switched to DMEM/F12 plus 10% FCS were intermediate in differentiation (DMEM/F12/FCS cells); DMEM/F12/FCS cells switched to serum-free DMEM/F12 plus 0.8 M NaCl to induce cornified envelopes were the most differentiated (DMEM/F12/NaCl cells). The differentiation status was characterized using immunohistochemistry and electron microscopy. NCF analysis was able to distinguish terminally differentiated epithelial cells (DMEM/F12/NaCl) from those less differentiated cells (KGM, DMEM/F12/FCS) in several emission (lambda ex 340 nm, lambda em 360-660 nm; lambda ex 365 nm, lambda em 400-700 nm; lambda ex 420 nm, lambda em 440-800 nm) and excitation scans (lambda ex 200-360 nm; lambda em 380 nm, lambda ex 240-430 nm; lambda em 450 nm, lambda ex 250-460 nm, lambda em 480 nm; lambda ex 270-500 nm, lambda em 520 nm). The ability to discriminate terminal differentiation in this in vitro model supports the concept of using NCF as an intermediate biomarker to monitor in vivo mucosal differentiation.

Chronic sinus disease associated with progressive mucosal disease is often a cause for anosmia. Despite aggressive allergic, medical, and surgical intervention, long-term relief of anosmia has been difficult to document. Fifty patients sought treatment for subjective anosmia and symptoms of progressive sinusitis and underwent endoscopic sinus surgery. After surgery 52% maintained significant improvement in smell by subjective measures that correlated with objective olfactory University of Pennsylvania Small Identification test ('UPSIT') results. Of the remaining patients, some had intermittent improvement, but most remained hyposmic or anosmic despite clinically well-healed ethmoid surgical beds. Of the preoperative and postoperative historical, clinical, and radiological data analyzed, severity of the presenting sinus disease (defined as stage II In the Kennedy staging criteria or disease extending beyond the ethmoids on preoperative computed tomography scan) and persistent mucosal disease in the surgical bed are associated with persistent anosmia (p = 0.005)

During the past 25 years, the Radiation Therapy Oncology Group (RTOG) has played a major role in head and neck cancer clinical research. The major research themes for recent and currently active trials have been: (a) combined modality therapy, (b) altered fractionation radiotherapy, (c) hypoxic cell sensitizers, (d) organ preservation, (e) chemoprevention, and (f) clinical/laboratory correlations. For advanced operable disease, the RTOG showed improved local-regional control with postoperative radiotherapy as compared to preoperative radiotherapy for carcinoma of the supraglottic larynx and hypopharynx. This established the use of surgery followed by postoperative radiotherapy as the standard treatment in subsequent RTOG and Intergroup trials for operable disease. For advanced inoperable disease, the RTOG demonstrated the feasibility of testing altered fractionation radiotherapy in a multiinstitutional clinical trials setting. A Phase III trial comparing hyperfractionation and accelerated fractionation to conventional fractionation is now in progress. Phase I/II combined modality studies established the efficacy of concurrent high-dose cisplatin and radiotherapy in the treatment of advanced disease and provided the basis for further testing in Phase III trials for nasopharyngeal carcinoma, larynx preservation, and high-risk advanced operable disease. Analysis of the extensive RTOG Head and Neck Cancer database established the incidence of second malignancies and their adverse impact on patients whose initial tumors were cured by radiotherapy, and provided the basis for chemoprevention trials. Recursive partitioning analysis identified 6 distinct prognostically homogeneous patient groups based on pretreatment tumor or patient characteristics and/or treatment variables. Retrospective analysis identified tumor p105 antigen density as an independent prognostic indicator in patients irradiated for head and neck cancer. Future trials will continue to focus on the reduction of morbidity and mortality, and improvement of the quality of life of head and neck cancer patients through innovative radiotherapy delivery, multimodality approaches, use of chemical and biological modifiers, and other novel therapies, identification of clinical and biological prognostic indicators, and prevention or diminution of acute morbidity and late complications of the disease and its treatment

This paper includes an overview of the research on late-onset auditory deprivation, an evaluation of the evidence from retrospective and prospective studies, recommendations for future research, and a consideration of the theoretical and clinical implications of the research. The studies reviewed offer convincing evidence of the late-onset auditory deprivation effect both in groups of listeners and in substantial numbers of individual listeners included in the group studies. The effect appears to be reversible in some cases with the use of amplification in the previously unaided ear. This preliminary evidence supports the recommendation of binaural amplification for persons with bilateral symmetric sensorineural hearing loss. There is much that is still unknown about the deprivation effect and recovery from deprivation. Longitudinal prospective studies are needed to obtain a better understanding of the role of subject-related variables and amplification-related variables on the magnitude and time course of the deprivation effect. Behavioral and electrophysiologic measures of monaural and binaural performance using speech and nonspeech stimuli would also further our understanding of the mechanisms underlying late-onset auditory deprivation

The purpose of this study was to ascertain the relation between preoperative glottal gap and postoperative vocal function in thyroplasty type I. Twenty-two of 64 patients who underwent thyroplasty type I between 1987 and 1994 were studied. In preoperative digitized laryngostroboscopic images, the glottal-gap, width (GGW), shape, and area were examined at the maximum closure of vibration and normalized by membranous vocal-fold length (MVFL). Postoperative vocal function analysis was performed with aerodynamic and acoustic measurements and compared with preoperative videostroboscopic images. In patients with preoperative posterior GGW of less than 10% of MVFL, postoperative vocal function was significantly better than in other patients. Although thyroplasty type I is an excellent medialization technique, it may need to be combined with a posterior closure procedure in patients with large posterior gaps