Faculty Bibliography

Genomes of solid tumors are characterized by gains and losses of regions, which may contribute to tumorigenesis by altering gene expression. Often the aberrations are extensive, encompassing whole chromosome arms, which makes identification of candidate genes in these regions difficult. Here, we focused on narrow regions of gene amplification to facilitate identification of genetic pathways important in oral squamous cell carcinoma (SCC) development. We used array comparative genomic hybridization (array CGH) to define minimum common amplified regions and then used expression analysis to identify candidate driver genes in amplicons that spanned <3 Mb. We found genes involved in integrin signaling (TLN1), survival (YAP1, BIRC2), and adhesion and migration (TLN1, LAMA3, MMP7), as well as members of the hedgehog (GLI2) and notch (JAG1, RBPSUH, FJX1) pathways to be amplified and overexpressed. Deregulation of these and other members of the hedgehog and notch pathways (HHIP, SMO, DLL1, NOTCH4) implicates deregulation of developmental and differentiation pathways, cell fate misspecification, in oral SCC development

BACKGROUND: An increasing incidence of oral carcinoma among young adults has been reported in the U.S. and Europe. Although the association between human papillomavirus infection and tonsillar carcinoma is now well established, to the authors' knowledge little is known about incidence trends in tonsillar carcinoma among younger adults. The objective of the current study was to explore the trends in both oral cavity and pharyngeal squamous cell carcinoma (SCC) in younger U.S. populations, in particular tongue and tonsillar SCC. METHODS: Using the 1973-2001 Surveillance, Epidemiology and End Results (SEER) database, we computed age, race, and site-specific trends of oral and pharyngeal (excluding nasopharynx) carcinoma incidence rates. The percent change (PC) and annual percent change (APC) were computed to explore trends in incidence rates over time. RESULTS: There were 2262 SCC of the oral cavity and 1251 SCC of the pharynx reported to the SEER program from 1973 to 2001 in adults aged 20-44 years. There was a statistically significant increase in the incidence of oral tongue SCC (APC = +2.1; P < 0.001), base of tongue SCC (APC = +1.7; P = 0.04), and palatine tonsil SCC (APC = +3.9; P < 0.001) among younger white individuals, whereas the incidence of SCC in all other oral and pharyngeal sites decreased or remained constant. CONCLUSIONS: The increase in tonsil SCC incidence from 1973 to 2001 paralleled the increase in tongue SCC, whereas SCC in all other oral and pharyngeal sites remained constant or decreased. This may suggest similar etiologic factors for SCC affecting the palatine tonsils and tongue in younger populations

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/HYPOTHESIS: To assess the value of both patient- and tumor-related factors of oropharyngeal squamous cell carcinoma in predicting patient outcome, with respect to the three primary subsites of the disease. It was hypothesized that the subsite has a significant impact on outcome. STUDY DESIGN: Historical cohort study. METHODS: A chart review was conducted of 126 patients diagnosed with squamous cell carcinoma of the oropharynx over a 10-year period. The oropharynx was divided into the following subsites: 1) base of tongue, 2) tonsil and pillars, and 3) uvula, soft palate, and posterior pharyngeal wall. Patient-related factors included age and gender. Tumor-related factors included American Joint Committee on Cancer stage, T stage, N stage, and grade. These factors were compared using the end points of disease-free survival and treatment response (complete response or partial response/no response). RESULTS: Tumor-related factors such as American Joint Committee on Cancer stage (P = .016) and T stage (P = .008) had a significant impact on treatment response. The American Joint Committee on Cancer stage (P = .030) and the T stage (P = .005) were also significant predictors of disease-free survival. Base-of-tongue lesions responded significantly worse to treatment than did tonsil and pillar or uvula, soft palate, and posterior pharyngeal wall lesions (P = .014). The disease-free survival for base-of-tongue cancer was significantly worse than for tonsil and pillar or for uvula, soft palate, and posterior pharyngeal wall cancer (P = .010). CONCLUSION: Patient-related factors such as age and gender were not significant in predicting disease-specific outcome. Important tumor-related factors were the American Joint Committee on Cancer stage and the T stage. Among the oropharyngeal subsites, squamous cell carcinoma of the base of tongue was associated with the worst outcome

The technique of endoscopic transnasal, nontransseptal, transsphenoidal pituitary surgery is gaining increasing popularity. Many pituitary surgical teams consider it the procedure of choice. It provides a rapid and safe approach to the sella turcica. Within the sella turcica, the endoscopes give the surgeon the ability to inspect around the corner and to remove residual tumor. The procedure avoids the complications related to the sublabial transeptal approach. Hospital stay is shorter

OBJECTIVE: To determine if age alone is a prognostic indicator of surgical outcomes for major head and neck procedures. DESIGN: Retrospective cohort study over a 4-year period. SETTING: Academic referral center, institutional practice, hospitalized care. PATIENTS: Included in this study were patients who had undergone ablative, reconstructive, and other major surgical procedures of the head and neck, including neck dissection, laryngectomy, maxillectomy, thyroidectomy with lymphadenectomy, and composite resection of the oral cavity with reconstruction, for both malignant and benign disease. MAIN OUTCOME MEASURES: Patient data and intraoperative and postoperative course factors were recorded. Comorbidity was graded using an Adult Comorbidity Evaluation 27 test, Charlson Comorbidity Index, and American Society of Anesthesiology score. Postoperative complications were dichotomized, and multiple logistic regression was used for data analysis. RESULTS: Medical chart review identified 157 cases. Analysis of data revealed that time under general anesthesia was the only factor consistently related to complications (P<.006), and it was the only factor consistently related to length of stay (P<.001). Analysis of major complications (6% incidence) as an outcome using univariate analysis resulted in a strong positive correlation with both comorbidity indexes: Adult Comorbidity Evaluation 27 (P = .002) and Charlson Comorbidity Index (P = .005). Multiple logistic regression showed no significant relationship between age 70 years or older (20% of patients) and either complications or hospital length of stay. CONCLUSIONS: Patient's age alone is not a prognostic indicator of surgical outcome for major head and neck procedures. However, comorbidity is an important predictive factor for postoperative complications in any age group. Time under general anesthesia showed a statistically significant relationship with complication rate and hospital length of stay in multivariate analyses. Consequently, prevention of complications should focus on optimizing preoperative comorbid conditions

OBJECTIVES: The sublabial transmaxillary approach to the pterygoid region was a popular one during the Caldwell-Luc, pre-endoscopic era. It was the procedure of choice for management of lesions of the pterygopalatine space, for internal maxillary artery ligation, and for vidian neurectomy. With the introduction of endoscopic instrumentation and techniques, the Caldwell-Luc procedure is rarely performed today. Also, because vidian neurectomy is performed less frequently, and because internal maxillary artery ligation for severe epistaxis has been replaced with transnasal endoscopic sphenopalatine artery ligation, the sublabial transmaxillary route is rarely used. We have found that combining the use of endoscopes via the sublabial approach and the transnasal endoscopic approach is very helpful for management of extreme lateral lesions of the sphenoid sinus, as well as the pterygoid region and the posterior orbit. METHODS: The records of patients who underwent a combined endoscopic transmaxillary-transnasal approach between 1994 and 2002 were reviewed. Indications for the procedure included extreme lateral sphenoid and pterygoid encephalocele (3 patients), pterygoid mucocele (2 patients), orbital apex lesion (2 patients), and pterygopalatine tumor (2 patients). RESULTS: Nine patients underwent the above-mentioned procedure. Wide and comfortable exposure of the involved region was achieved in all cases. Compared with the transnasal approach, the working distance, working comfort, and maneuverability of instruments were significantly enhanced. There were no major complications related to the approach. Because the maxillary wall opening is very small, infraorbital hypoesthesia is very limited and of short duration. CONCLUSIONS: Combining the transmaxillary and transnasal approaches for endoscopic management of pterygoid, lateral sphenoid, and retrobulbar orbit lesions provides excellent exposure and avoids the limited working angle and surgical struggle that may be associated with the use of the transnasal approach alone

Recurrent aphthous stomatitis (RAS) and recurrent oral herpes-including recurrent herpes labialis (RHL) and recurrent intraoral herpes (RIH)--are two of the most common oral ulcerative disorders. Despite their benign nature, both may be associated with pain, discomfort, and social avoidance. This article presents methods for dental professionals to diagnose and manage patients with these conditions