Chad A. Zender

Site‐specific production of TGF‐β in oral mucosal and cutaneous wounds

Wound healing in the oral mucosa is clinically distinguished by rapid healing and lack of scar formation compared with dermal wounds. Mechanisms of favorable mucosal healing are yet to be elucidated. Utilizing a murine model of equivalent‐size mucosal and skin wounds, we verified the rapid reepithelializaton and reduction in scarring of oral wounds reported in humans. Collagen fibrillar structure in oral wounds rapidly approached the size of normal collagen fibrils, while the collagen ultrastructure in skin remained immature through the later phases of healing. To determine whether the transforming growth factor‐β (TGF‐β) contributes to the lack of scar formation in oral mucosa, we compared the expression and production in oral and skin wounds. The RNase protection assay demonstrated significantly lower levels of TGF‐β1 expression in oral wounds compared with dermal wounds, and no changes were observed in the expression levels of TGF‐β2 or TGF‐β3. ELISA analysis confirmed that oral wounds contained lower levels of TGF‐β1 levels compared with dermal wounds, along with a significant increase in the ratio of TGF‐β3 to ‐β1. These findings showed reduced scarring in oral wounds at the ultrastructural level, and provide evidence that site‐specific differences in TGF‐β production contributes to the superior healing of oral wounds.

Dose- and age-dependent alterations in choline acetyltransferase (ChAT) activity, learning and memory, and thyroid hormones in 15- and 30-day old rats exposed to 1.25 or 12.5 ppm polychlorinated biphenyl (PCB) beginning at conception

1. Polychlorinated biphenyls (PCB) were released into the environment through improper disposal for decades, causing widespread contamination. Slow biodegradation and lipophilic properties of PCB caused its persistence and concentration through food webs. Exposure to these environmental contaminants through maternal transfer during early development has been associated with neurological and endocrinological alterations in several different organisms. 2. The present study extended a preliminary investigation which suggested low level exposure to PCB altered acetylcholine biosynthesis enzyme, choline acetyltransferase (ChAT), activity in the hippocampus and basal forebrain and caused aberrations in thyroid hormone and behavior. 3. Dietary exposure of 15-day-old animals to 1.25 ppm of Aroclor 1254 (LPCB) during gestation and lactation significantly elevated ChAT activity in both areas of the brain. Animals exposed to 12.5 ppm of Aroclor 1254 (HPCB) until 15 days of age demonstrated significant elevations of ChAT activity in the basal forebrain. Thyroxine (T4) concentrations were slightly elevated in 15-day-old LPCB animals and significantly depressed in HPCB exposed pups; triiodothyronine (T3) concentrations were not altered. 4. At 30 days both LPCB and HPCB treatment groups displayed significantly depressed ChAT activity in both areas of the brain. T3 and T4 concentrations were subnormal, although T4 was not significantly depressed in LPCB animals. 5. In the Morris water maze all animals, when tested between 25 and 29 days of age, improved their latency time to the platform over 10 spatial learning trials. However, when combined means of trials 8-10 were compared, HPCB exposed animals had significantly increased latency time to the podium compared to control and LPCB animals.

Distant Metastases in Head-and-Neck Squamous Cell Carcinoma Treated With Intensity-Modulated Radiotherapy

PURPOSE To determine the pattern and risk factors for distant metastases in head-and-neck squamous cell carcinoma (HNSCC) after curative treatment with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS This was a retrospective study of 284 HNSCC patients treated in a single institution with IMRT. Sites included were oropharynx (125), oral cavity (70), larynx (55), hypopharynx (17), and unknown primary (17). American Joint Committee on Cancer stage distribution includes I (3), II (19), III (42), and IV (203). There were 224 males and 60 females with a median age of 57. One hundred eighty-six patients were treated with definitive IMRT and 98 postoperative IMRT. One hundred forty-nine patients also received concurrent cisplatin-based chemotherapy. RESULTS The median follow-up for all patients was 22.8 months (range, 0.07-77.3 months) and 29.5 months (4.23-77.3 months) for living patients. The 3-year local recurrence-free survival, regional recurrence-free survival, locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 94.6%, 96.4%, 92.5%, 84.1%, and 68.95%, respectively. There were 45 patients with distant metastasis. In multivariate analysis, distant metastasis was strongly associated with N stage (p = 0.046), T stage (p < 0.0001), and pretreatment maximum standardized uptake value of the lymph node (p = 0.006), but not associated with age, gender, disease sites, pretreatment standardized uptake value of the primary tumor, or locoregional control. The freedom from distant metastasis at 3 years was 98.1% for no factors, 88.6% for one factor, 68.3% for two factors, and 41.7% for three factors (p < 0.0001 by log-rank test). CONCLUSION With advanced radiation techniques and concurrent chemotherapy, the failure pattern has changed with more patients failing distantly. The majority of patients with distant metastases had no local or regional failures, indicating that these patients might have microscopic distant disease before treatment. The clinical factors identified here should be incorporated in future clinical trials.

Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell carcinoma of the head and neck

The purpose of this study was to establish the efficacy and toxicities of concurrent bevacizumab and docetaxel with radiation for locally advanced head and neck squamous cell carcinoma (HNSCC).

Utility of SPECT/CT for periparotid sentinel lymph node mapping in the surgical management of head and neck melanoma

PURPOSE Sentinel lymph node (SLN) biopsy is instrumental in staging and treatment of cutaneous melanoma. SPECT/CT, single-photon emission computed tomography (SPECT) integrated with computed tomography (CT), increases the accuracy of SLN mapping to improve surgical planning. SPECT/CT can correct for signal scatter to prevent masking, which is especially common in the head and neck. For periparotid lymph nodes SPECT/CT may improve localization of SLNs compared to lymphoscintigraphy. MATERIALS/METHODS Hospital charts were reviewed for 14 patients with melanoma and suspected lymphatic drainage to the parotid region who received lymphoscintigraphy followed by SPECT/CT prior to surgical excision and SLN. RESULTS Overall, SPECT/CT provided data, which changed management in 57% of patients. CONCLUSIONS Fifty-seven percent of our patients benefited from use of SPECT/CT. The distinction between level II and parotid sentinel lymph nodes was clearly identified through SPECT/CT images. We believe that patients with melanoma draining to the parotid region would benefit from SPECT/CT SLN mapping.

Why do patients with head and neck squamous cell carcinoma experience distant metastases: can they be prevented?

Purpose of reviewThis article will examine recent publications that enhance our understanding of this process, and current areas of investigation for therapeutic intervention in preventing and treating metastatic disease. Recent findingsRecent investigations have led to insights into the mechanisms of cellular adhesion, invasion, and angiogenesis. E-cadherin, integrins, and selectins are all pivotal in cell-cell adhesion and communication. Recent advances in the area of tumor angiogenesis have led to our discovery of endostatin, an anti-angiogenic peptide that has potential in treating metastatic head and neck cancer. Current trials looking at sentinel node mapping may allow us to evaluate the nodal status of early head and neck cancer and identify a subset of patients at risk for distant metastasis. SummaryAs our understanding of metastatic disease increases, so will our ability to intervene in the various pathways involved in metastatic evolution. Metastatic cells are likely to respond differently to chemotherapeutic agents. Agents inhibiting specific aspects of invasion, adhesion, and angiogenesis will need to be combined to intervene at these key steps. Continued investigation into the biology of the epidermal growth factor receptor has led to an increased understanding of the mechanisms of abrogation of apoptosis, increased cellular motility, and metastasis. Inhibition of the epidermal growth factor receptor pathway with the monoclonal antibody C-255 has been shown to inhibit these processes and will likely be effective in reducing the development of distant metastasis.

Temporal bone osteoradionecrosis after surgery and radiotherapy for malignant parotid tumors.

Objective: To assess the incidence of osteoradionecrosis (ORN) of the temporal bone after surgery with radiotherapy for malignant parotid tumors. Setting: A tertiary care, academic medical center. Patients: All patients who underwent surgical resection with postoperative radiotherapy (RT) for a malignant parotid tumor between July 1988 and July 2007. Interventions: A retrospective chart analysis to determine the extent of surgery, the RT parameters, and the incidence of ORN of the temporal bone. Main Outcome Measures: The incidence of ORN in 3 subgroups of patients. Results: The 221 patients with malignant parotid tumors who underwent surgical resection with postoperative RT were divided into groups 1, parotidectomy only; 2, parotidectomy with mastoidectomy; and 3, parotidectomy with subtotal petrosectomy. The overall incidence of temporal bone ORN in group 1 was 2 (2%) of 106; in group 2, 8 (13%) of 64; and in group 3, 0 (0%) of 51. Conclusion: The incidence of temporal bone ORN is higher after mastoidectomy for facial nerve identification or resection in patients undergoing parotidectomy with postoperative radiotherapy. Oversew of the ear canal with mastoid obliteration should be considered in this subgroup of patients to avoid this long-term complication of radiotherapy used in the treatment of malignant parotid tumors.

Facial nerve schwannoma.

Purpose of reviewThe purpose of this review is to summarize the current literature on facial nerve schwannoma and make practical recommendations based on best practices for the management of this difficult but benign neoplasm. Recent findingsFacial nerve schwannoma can be asymptomatic or can present with progressive or acute facial nerve palsy. Associated otological symptoms such as conductive and/or sensorineural hearing loss can occur. The tumor is usually slow-growing and can involve multiple segments of the nerve. Radiographic imaging and facial nerve electrical testing can be helpful in treatment planning. Options for management can include observation, decompression, stripping, resection with grafting, and possibly radiotherapy. Future adjunctive therapies to improve facial nerve function may include electrical stimulation, steroid hormones, and possibly stem cell therapy. SummaryTreatment of facial schwannoma is individualized based on patient symptoms, history, and clinicoradiographic evaluation. Not all patients require surgery. As the tumor can involve multiple segments of the nerve, the surgeon attempting removal should be familiar with modern neurotological surgical techniques. Ongoing translational research will hopefully allow us to decrease facial nerve morbidity in these patients.

Multi-institutional investigation of the prognostic value of lymph nodel yield in advanced-stage oral cavity squamous cell carcinoma

Although existing literature provides surgical recommendations for treating occult disease (cN0) in early‐stage oral cavity squamous cell carcinoma (SCC), a focus on late‐stage oral cavity SCC is less pervasive.

Etiologic causes of late osteocutaneous free flap failures in oral cavity cancer reconstruction

To evaluate perioperative complications in a homogeneous cohort undergoing microvascular osteocutaneous free flap (OCFF) reconstruction following segmental mandibulectomy for advanced oral cancer and to identify the causes of late OCFF failures.