Derrick T. Lin

Cyclooxygenase-2: A novel molecular target for the prevention and treatment of head and neck cancer

Cyclooxygenase‐2 (COX‐2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of premalignant and malignant conditions, including oral leukoplakia and squamous cell carcinoma of the head and neck. Increased levels of COX‐2 may contribute to carcinogenesis by modulating xenobiotic metabolism, apoptosis, immune surveillance, and angiogenesis. In experimental models, newly developed selective COX‐2 inhibitors suppress the formation of tumors, including tongue cancer. These findings provided a rationale for a number of chemoprevention trials that are underway. Selective COX‐2 inhibitors also suppress the growth and metastases of established tumors and enhance the anticancer activity of both radiotherapy and chemotherapy in experimental animals. In this review, evidence is presented that inhibition of COX‐2 represents a promising strategy to prevent or possibly treat human head and neck cancers.

Incidence of Inadvertent Parathyroid Removal During Thyroidectomy

Objectives To assess the incidence of unintentional parathyroid removal during routine thyroidectomy and to identify factors that might predict patients at high risk.

Inhibition of cyclooxygenase-2: an approach to preventing cancer of the upper aerodigestive tract.

Multiple lines of evidence suggest that cyclooxygenase‐2 (COX‐2), an inducible form of COX, represents a potential pharmacologic target to prevent cancer. Key data suggesting a causal relationship between increased COX‐2 activity and carcinogenesis and possible mechanisms of action of COX‐2 in this context will be discussed. The possibility that COX‐2 represents a pharmacological target for preventing upper aerodigestive cancers (head and neck, lung) will be emphasized. Importantly, clinical trials have been initiated to assess the chemopreventive properties of selective COX‐2 inhibitors.

Current concepts in lip reconstruction.

Purpose of reviewApproximately 25% of all oral cavity carcinomas involve the lips, and the primary management of these lesions is complete surgical resection. The management of the resulting lip defect remains a significant reconstructive challenge, requiring meticulous preoperative planning and surgical technique to optimize the functional and cosmetic outcome. Reviewed here are the accepted techniques of lip reconstruction, as well newer techniques that have been reported. Recent findingsThere have been no major advances in lip reconstruction; rather, continued improvement on accepted techniques. The main goals of reconstruction remain the restoration of oral competence, maintenance of oral opening, and the restoration of normal anatomic relations such that both the active (smile) and passive (form) cosmetic outcome is acceptable. The reconstruction should be tailored to the individual needs of the patient and should take into account the patient’s condition, local tissue characteristics, previous treatment(s), and functional needs (eg, denture use), in addition to the size and location of the defect. SummaryThe lips play a key role in facial expression, speech, and eating. This requires meticulous attention to preoperative planning and surgical technique to maximize the functional and cosmetic outcome. It is important to assess local tissue characteristics (skin laxity) and previous treatment (surgery and/or irradiation) before the surgical plan is made final. Local tissue should be used whenever possible to provide the least donor site morbidity and the best overall tissue color and texture match. Whenever possible, dynamic reconstruction should be attempted. Careful preoperative assessment and planning will allow the surgeon to reach an acceptable balance between form and function with the reconstruction.

Extent of surgery in the management of locally advanced sinonasal malignancies.

The relative importance of surgery within multimodality regimens commonly used to treat advanced sinonasal malignancies remains unknown.

Esthesioneuroblastoma: The Massachusetts Eye and Ear Infirmary and Massachusetts General Hospital Experience with Craniofacial Resection, Proton Beam Radiation, and Chemotherapy

OBJECTIVES To determine the efficacy of craniofacial resection and proton radiation for the management of esthesioneuroblastoma (ENB). DESIGN A retrospective chart review was performed of all patients presenting with ENB and completely managed at the Massachusetts General Hospital (MGH) and the Massachusetts Eye and Ear Infirmary (MEEI) from 1997 to 2006. SETTING A tertiary referral center. MAIN OUTCOME MEASURES Disease-free and overall survival. PARTICIPANTS All patients presenting with ENB and completely managed at the MGH and the MEEI from 1997 to 2006. RESULTS Ten patients were identified with a median follow-up time of 52.8 months. Average age at presentation was 45 years. Nasal obstruction was the most common presenting symptom. Three patients presented with Kadish stage B disease and seven with stage C. No patient had evidence of cervical or metastatic disease at presentation. Seven patients were treated with craniofacial resections (CFR) followed by proton beam radiation with or without chemotherapy. Three patients were treated with initial chemotherapy with no response. They subsequently underwent CFR followed by proton beam radiation. The 5-year disease-free and overall survival rates were 90% and 85.7%, respectively, by Kaplan-Meier analysis. No patient suffered any severe radiation toxicity. CONCLUSION ENB can be safely and effectively treated with CFR followed by proton beam irradiation. Proton irradiation may be associated with less toxicity than photon irradiation. The role of chemotherapy remains unclear.

Management outcomes following lateral temporal bone resection for ear and temporal bone malignancies.

Objective To evaluate clinical outcomes following lateral temporal bone resection (LTBR) for management of malignancies involving the ear or temporal bone. Subjects and Methods A retrospective medical record review was performed on patients receiving LTBR for management of malignancies involving the ear or temporal bone between 1990 and 2007. Results In this group of 35 patients, the mean age was 62.7 years, with tumor histopathologies including squamous cell carcinoma (SCC, 20), basal cell carcinoma (BCC, 7), adenoid cystic carcinoma (ACC, 7), and adenocarcinoma (1). The 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 77%, 79%, and 52%, respectively. Complete resection resulted in improved OS, DSS, and DFS (P < 0.004 for each) and reduced local recurrence (P < 0.001). Conclusions In patients with carcinomas of the ear and temporal bone, upfront excision including LTBR is an effective management when combined with postoperative radiation therapy. Complete removal of all disease may improve survival and decrease recurrence.

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined HNSCC subtypes by their malignant and stromal composition and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis.

Immunohistochemical characterization of human olfactory tissue.

The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction.

PROTON RADIATION THERAPY FOR PRIMARY SPHENOID SINUS MALIGNANCIES: TREATMENT OUTCOME AND PROGNOSTIC FACTORS

The purpose of this study was to determine treatment outcome and prognostic factors in patients with locally advanced primary sphenoid sinus malignancy treated with proton radiation therapy.