Faculty Bibliography

Beta-6 Integrin, tenascin-C, and MMP-1 (matrix metalloproteinase-1) are invasion-related proteins that are frequently overexpressed in many human malignancies. The objective of this study was to determine whether there is overexpression of these molecules in three types of salivary neoplasms showing markedly different behavior. A total of 55 formalin-fixed, paraffin-embedded archived specimens comprising 19 adenoid cystic carcinomas (ACC), 18 polymorphous low-grade adenocarcinomas (PLGA) and 18 pleomorphic adenomas (PA) were utilized in this study. A standard immunohistochemical technique was used to determine the expression levels of beta-6 integrin, tenascin-C, and matrix metalloproteinase-1 (MMP-1) proteins. Sections were assessed semiquantitatively, and tumors were divided into two groups, low-expressors (0-1+) and high-expressors (2-3+) for statistical analysis. Staining was graded as 0 (<1% positive tumor cells), 1+ (<25% positive tumor cells), 2+ (25-50% positive tumor cells), and 3+ (>50% positive cells). The results showed that the malignant tumors were higher expressors of beta-6 than the benign tumors. ACCs showed significantly higher expression of beta-6 than PAs (p=0.04). No significant difference was observed between ACCs and PLGAs. beta-6 expression was rarely seen in normal salivary gland epithelium and was occasionally present in mucosa overlying the tumors. PAs were high-expressors of tenascin-C with a significant difference relative to ACCs (p=0.03). A majority of tumors in all three tumor types showed high expression of MMP1 with expression significantly greater in the PAs compared to ACCs (p=0.008). We conclude that ACCs and PLGAs express beta-6, tenascin-C, and MMP-1, but that their expression patterns are not significantly different. beta-6 appears to be more closely associated with the malignant tumors, and MMP-1 more closely associated with the benign tumors. We believe that beta-6, tenascin-C, and MMP-1 proteins are part of the molecular repertoire used by salivary tumors for malignant invasion and benign tumor expansion

OBJECTIVES: To build on work in laryngology and oral biology that suggests utility in the assay of secretions collected from wound sites as a predictive instrument to determine which infants will likely develop subglottic stenosis following endotracheal intubation and to document and describe the wound-healing process. DESIGN: Prospective, randomized design. INTERVENTION: Laser-induced subglottic injury was established in 3 rabbits. Secretions were collected from the subglottic region at 6 time points from days 4 to 21 following injury and from 4 uninjured control airways. The secretions were then subjected to enzyme-linked immunoassays for interleukin 1 beta and prostaglandin E2. SUBJECTS: Three adult New Zealand white rabbits. MAIN OUTCOME MEASURES: Interleukin 1 beta and prostaglandin E2 levels. RESULTS: Measurable amounts of both mediators were obtained. Furthermore, different temporal patterns of expression were observed with interleukin 1 beta, showing increased levels on days 4 to 18, and with prostaglandin E2, showing increased levels on days 7 to 18. These results concur with emerging data regarding the role of each mediator in the wound-healing process. CONCLUSION: Although in its infancy, the analysis of secretions collected from the site of injury in the subglottis may have utility in the management of patients following intubation-related trauma

The purpose of this retrospective study was to evaluate the extent to which an early Le Fort III osteotomy affects the position and eruption of the permanent maxillary first and second molars. To test the null hypothesis that there are no changes in eruption patterns, 31 patients diagnosed with craniosynostoses (13 with Crouzon's syndrome, nine with Apert's syndrome, eight with Pfeiffer's syndrome, and one with Carpenter's syndrome) with a mean age at the time of surgery of 5.3 +/- 1.3 years were studied. All patients underwent a Le Fort III osteotomy performed by a single surgeon to correct the anatomical deformity for functional and psychosocial reasons. Eighteen patients with craniosynostoses who had not been operated on (11 with Crouzon's syndrome, four with Apert's syndrome, and three with Pfeiffer's syndrome) served as controls; they had a mean age of 21.2 +/- 9.5 years. First and second molar positions and eruption patterns were assessed separately on panoramic radiographs by three observers. For the patients who underwent surgery, long-term evaluation showed that although 79 percent of all first molars erupted compared with 100 percent for the control group (p < 0.001), only 18 percent of all second permanent molars erupted compared with 89 percent for the control group (p < 0.0001). The authors conclude that in a significant minority of cases, early Le Fort III osteotomy affects first molar eruption, whereas the probability of second molar eruption is significantly decreased in the majority of cases. Therefore, Le Fort III osteotomy sites should be positioned distal to the second molar tooth buds. If this is not possible, patients, parents, and dental professionals should be made aware of these early postosteotomy sequelae so that later treatment planning can be enhanced.

The management of base of tongue cancer has evolved steadily over time. Organ preservation with primary radiation therapy has produced excellent oncologic and functional outcomes. Concomitant chemotherapy has become important in patients with locoregionally advanced disease. Planned neck dissection after organ preservation therapy continues to be an integral step for regional control. This article reports the results of a literature review of base of tongue cancer emphasizing a multidisciplinary approach to obtain optimal results in terms of cure and quality of life.

To analyze the impact of resection margin status and histologic prognosticators on local recurrence (LR) and overall survival (OS) for patients with oral squamous cell carcinoma (OSCC). This study was both retrospective and prospective in design. Cohort 1 refers to the entire group of 292 patients with OSCC. The slides from the earliest resection specimens from Cohort 1 were examined in an exploratory manner for multiple parameters. Cohort 2 refers to a subset of 203 patients, who did not receive any neoadjuvant therapy and had outcome data. Cohort 3 represents a subset of Cohort 2 (n = 168) wherein the histologic resection margin status could be reconfirmed. Cohort 4 refers a subset of 85 patients with tongue/floor of mouth tumors. Margin status was designated as follows: group 1, clearance of > or =5 mm with intraoperative analysis, no need for supplemental margins (n = 46); group 2, initial margins were measured as <5 mm during intraoperative frozen section; supplemental resection margins were negative on final pathology (n = 73); group 3, the final pathology revealed resection margins <5 mm (n = 30); group 4, the final pathology revealed frankly positive resection margins (n = 19). The endpoints of LR and OS were queried with respect to T stage, tumor site, margin status, and numerous histologic variables, by Cox regression and Kaplan-Meier survival analyses. Tumor stage (T) was significantly associated with LR (P = 0.028). Kaplan-Meier analysis for stage and for intraoral site was significantly associated with LR for T4 tumors. The increased likelihood of LR was higher for T4 OSCC of the buccal mucosa (75%), sinopalate (50%), and gingiva (100%) compared with mobile tongue (27%), and oropharynx (13%) (P = 0.013). Margin status was not associated with LR or OS (Cohort 3). This was so when all tumors were grouped together and when separate analyses were performed by tumor stage and oral subsite. No significance was demonstrated when margin status was examined for patients with similar treatment (surgery alone or surgery with adjuvant RT). However, the administration of adjuvant RT did significantly increase local disease-free survival (P = 0.0027 and P = 0.001 for T1 and T2 SCC, respectively). On exploratory analyses of histologic parameters, worst pattern of invasion was significantly associated with LR (P = 0.015) and OS (P < 0.001). Perineural invasion involving large nerves (>1 mm) was associated with LR (P = 0.005) and OS (P = 0.039). Limited lymphocytic response was also significantly associated with LR (P = 0.005) and OS (P = 0.001). When used as covariates in a multivariate Cox regression model, worst pattern of invasion, perineural invasion, and lymphocytic response were significant and independent predictors of both LR and OS, even when adjusting for margin status. Thus, these factors were used to generate our risk assessment. Our risk assessment classified patients into low-, intermediate-, or high-risk groups, with respect to LR (P = 0.0004) and OS (P < 0.0001). This classification retained significance when examining patients with uniform treatment. In separate analyses for each risk group, we found that administration of adjuvant radiation therapy is associated with increased local disease-free survival for high-risk patients only (P = 0.0296) but not low-risk or intermediate-risk patients. Resection margin status alone is not an independent predictor of LR and cannot be the sole variable in the decision-making process regarding adjuvant radiation therapy. We suggest that the recommendation for adjuvant radiation therapy be based on, not only traditional factors (inadequate margin, perineural invasion, bone invasion) but also histologic risk assessment. If clinicians want to avoid the debilitation of adjuvant radiation therapy, then a 5-mm margin standard may not be effective in the presence of high-risk score

Anterior craniofacial resection has become a standard procedure for management of lesions of the anterior skull base. During the last 2 decades, modifications of the classic anterior craniofacial resection have been reported. With the introduction of endoscopic sinus techniques and instrumentation, surgeons have begun to use endoscopic approaches for management of anterior skull base lesions. This article describes endoscopic modifications of anterior craniofacial resection

OBJECTIVES/HYPOTHESIS: The objective was to determine whether there is an increased incidence of otorrhea in young children with tympanostomy tubes who swim and bathe without water precautions as compared with children who use water precautions in the form of ear plugs. STUDY DESIGN: Prospective, randomized, investigator-blinded, controlled trial. METHODS: Two hundred one children (age range, 6 mo-6 y) who had undergone bilateral myringotomy and tube insertion were randomly assigned into one of two groups: swimming and bathing with or without ear plugs. Children were seen monthly for 1 year and whenever there was intercurrent otorrhea. RESULTS: Ninety children with and 82 children without ear plugs returned for at least one follow-up visit. Mean (SD) duration of follow-up was 9.4 (4.1) months for the children with ear plugs and 9.1 (4.4) months for the children without ear plugs. Forty-two children (47%) who wore ear plugs developed at least one episode of otorrhea, as compared with 46 (56%) who did not use ear plugs (logistic regression adjusting for stratification variables, P = .21). The mean (SD) rate of otorrhea per month was 0.07 (0.31) for the children who wore ear plugs as compared with 0.10 (0.31) for the children who did not wear ear plugs (Poisson regression adjusting for stratification variables, P = .05). CONCLUSION: There is a small but statistically significant increase in the rate of otorrhea in young children who swim and bathe without the use of ear plugs as compared with children who use ear plugs. Because the clinical impact of using ear plugs is small, their routine use may be unnecessary

Cyclooxygenase-2 (COX-2) is a promising pharmacologic target for preventing aerodigestive malignancies. In this study, we investigated the effects of tobacco smoke on the expression of COX-2 in oral mucosa. An approximately 4-fold increase in amount of COX-2 mRNA was observed in the oral mucosa of active smokers versus never smokers. Thus, a series of in vitro studies were carried out to elucidate the mechanism by which tobacco smoke induced COX-2. Treatment of a nontumorigenic oral epithelial cell line (MSK-Leuk1) with a saline extract of tobacco smoke (TS) stimulated COX-2 transcription, resulting in increased amounts of COX-2 mRNA, COX-2 protein, and prostaglandin E(2) (PGE(2)) synthesis. Exposure of cells to TS also caused an increase in epidermal growth factor receptor (EGFR) tyrosine kinase activity. Both an inhibitor of EGFR tyrosine kinase activity and a neutralizing anti-EGFR antibody blocked TS-mediated induction of COX-2. To define the mechanism by which TS activated EGFR, the release of amphiregulin and transforming growth factor alpha, two ligands of the EGFR, was measured. Exposure to TS caused a rapid increase in the release of both ligands. TS also markedly induced the expression of mRNAs for amphiregulin and transforming growth factor alpha. Importantly, increased expression of both ligands was also detected in the oral mucosa of active smokers. Taken together, these results suggest that activation of EGFR signaling contributes to the elevated levels of COX-2 found in the oral mucosa of smokers. Moreover, these findings strengthen the rationale for determining whether inhibitors of COX-2 or EGFR tyrosine kinase activity can reduce the risk of tobacco smoke-related malignancies of the aerodigestive tract

OBJECTIVES: This article presents the first report of cochlear implantation in a patient with congenital aural atresia, microtia, dysplastic cochlea and internal auditory canals, and bilateral profound sensorineural hearing loss (HL). This rare combination requires special management considerations. Preoperative issues include thorough evaluation of computed tomography and magnetic resonance imaging to determine favorable anatomy, cochlear implantation candidacy, and surgical planning. Intraoperative concerns include incision placement, surgical approach to the middle ear, and abnormal facial nerve anatomy. Postoperative use of a special headset combining a microphone and transmitter coil is required. STUDY DESIGN: Case report and literature review. METHODS: The patient's chart was reviewed for diagnostic studies, operative strategy, and postoperative auditory stimulation and testing. A literature review was performed. RESULTS: A 2-year-old male presented with bilateral aural atresia, microtia, and profound sensorineural HL. Imaging studies revealed multiple abnormalities of the cochlea, vestibule, and internal auditory canal, all of which were more favorable on the right side. An incision was designed to accommodate future microtia repair. The cochlear implant was placed without difficulty by way of a facial recess approach to the middle ear. Postoperative results include the detection of Ling sounds and voices in the environment as well as the ability to locate sounds. CONCLUSIONS: This is the first report of cochlear implantation in a patient with bilateral aural atresia, microtia, and profound sensorineural HL in conjunction with multiple inner ear abnormalities. Close collaboration among the otologist, neuroradiologist, and plastic surgeon is essential to coordinate surgical management and optimize cosmetic and functional outcomes in this unique population