Faculty Bibliography

OBJECTIVES/HYPOTHESIS: To study the microscopic anatomy of normal oral tissues in vivo using confocal reflectance microscopy (CRM). This novel and noninvasive imaging modality can define and characterize healthy oral mucosa and thus this work serves as the foundation for studying oral diseases in vivo. STUDY DESIGN: This was a pilot observational cohort study comparing noninvasive CRM images with histology. MATERIALS AND METHODS: Lip and tongue mucosa were imaged by CRM in six healthy human subjects. In CRM living tissue is illuminated by a laser source and backscattered (or reflected) light is collected by a detector. Image contrast is determined by natural differences in refractive indices of organelles and other subcellular structures within the tissues. Gray-scale images were displayed in real-time on a video monitor and represented horizontal (en face) optical sections through the tissue. Motion of the oral tissue relative to the objective lens was minimized with a tissue stabilizer. After imaging, biopsies were taken from the same site of lip mucosa to correlate noninvasive confocal images with conventional histology. RESULTS: Confocal images correlated well with conventional histology, both qualitatively (visual analysis) and quantitatively (stereology). Imaging was possible up to depths of 490 and 250 microm in the lip and tongue, respectively. Cells and organelles including nuclei, circulating blood cells, and extracellular matrix were clearly observed. CONCLUSION: CRM provides details of normal human oral mucosa at the cellular level without the artifacts of histological processing, and thus has the potential for further development and use in clinical practice as a diagnostic tool for the early detection of oral cancer and precancer

BACKGROUND: This study was performed to assess the relationship between Hashimoto's thyroiditis and the development, presentation, management, and outcome of papillary thyroid carcinoma. METHODS: Two complementary analytic methods were used. The clinical study was a retrospective case-control study, including patients seen with papillary thyroid carcinoma presenting during a 12-year period. We also used a systematic literature review to identify suitable reports and meta-analysis to statistically combine published results. RESULTS: The prevalence of Hashimoto's thyroiditis is significantly higher in patients with papillary thyroid cancer (odds ratio, 1.89; 95% CI, 1.02-3.50). These patients typically have a dominant nodule, 44% of which are discovered incidentally on routine examinations. Fine-needle aspiration has a sensitivity of 91% for the identification of papillary cancer. The prognostic variables at the time of a diagnosis of papillary cancer and the approach to management are not altered by the presence of coexistent Hashimoto's thyroiditis. In addition, the rate of surgical complications was not higher in patients with coexistent Hashimoto's disease. Meta-analysis suggested a positive correlation between Hashimoto's disease and disease-free survival (r = 0.09; 95% CI, 0.05-0.12) and overall survival (r = 0.11; 95% CI, 0.07-0.15). CONCLUSIONS: There is an increased prevalence of Hashimoto's thyroiditis in patients with papillary thyroid carcinoma. The presence of coexistent Hashimoto's thyroiditis does not affect the diagnostic evaluation or management of papillary thyroid cancers. The survival of patients who have papillary thyroid cancers may be superior in coexistent Hashimoto's thyroiditis

Recurrent pleomorphic adenomas (RPAs) of the parotid gland are an uncommon but challenging problem. The records of 31 patients with RPAs were reviewed to assess the clinical presentation and treatment results. More than half of these patients underwent total parotidectomy. Local control was achieved in 94% of patients at 7 years (median follow-up 7.3 years). Patients who had surgery for recurrence after a formal parotidectomy were more likely to have another recurrence (63% local control at 7 years) than patients whose initial procedure was a limited excision (100% local control at 7 years; P < 0.01). Better local control was seen in 11 patients who received postoperative irradiation (100% at 10 years) than in 20 patients who did not (71% at 10 years; P < 0.28). Adequate surgical resection yields an acceptable local control rate in patients with RPAs. Postoperative radiation therapy may improve control in patients at high risk for another recurrence

OBJECTIVE/HYPOTHESIS: Hemangiopericytomas are uncommon neoplasms of vascular origin that may arise in the head and neck. Their rare occurrence and variable malignant potential have limited attempts to characterize their clinical behavior. This study reviews the experience in treating hemangiopericytomas of the head and neck at a single institution. STUDY DESIGN: Retrospective. METHODS: The records of 12 patients with hemangiopericytomas of the head and neck presenting between 1979 and 1995 were reviewed. Site of origin included the neck (4), oral cavity (3), parotid (2), orbit (1), maxillary sinus (1) and mandible (1). Five patients had lesions characterized as high or intermediate grade histologically, and six had lesions characterized as low grade. RESULTS: Nine patients were treated with curative intent; three presented either with pulmonary metastasis (2) or unresectable primaries (1) and were treated with radiation therapy and/or palliative Adriamycin-based chemotherapy. Patients treated with curative intent underwent a variety of surgical resections dictated by tumor location and size. Four patients received postoperative radiation therapy to a median dose of 60 Gy, for positive surgical margins (2), high-grade histology (1) or a recurrent lesion (1). Five-year overall survival in patients treated surgically was 87.5%. A single mortality occurred in a patient with a recurrent high-grade lesion who failed at local, regional, and distant sites. Median follow-up of survivors was 73 months. CONCLUSION: The clinical behavior of hemangiopericytomas appears to be related to their histological grade. Aggressive local therapy including surgery and radiation therapy appears to be effective in providing tumor control

Unilateral vocal cord paralysis following pneumonectomy has profound effects on deglutition, phonation, protection of the airway, and generation of an adequate cough. If untreated in patients with limited pulmonary reserve, these detrimental effects can have devastating consequences. Several techniques are currently available which allow adequate medialization and rehabilitation of the paralyzed vocal cord. Adequate diagnosis and treatment can minimize the negative consequences associated with vocal cord paralysis following pneumonectomy

G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S-phase fraction (8.6%-36.6%) and was proportional to response to G207 therapy in vitro (1%-93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 +/- 0.60 cm(3) vs. 9.16 +/- 3.70 cm(3), P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 +/- 10 nodules in G207-treated livers vs. 80 +/- 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S-phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases

BACKGROUND: Allergic contact dermatitis (ACD) is a common and often challenging clinical problem. In vivo near-infrared confocal reflectance microscopy (CM) is a new vital microscopy technique. OBJECTIVE: CM was used to evaluate acute ACD. METHODS: Patch testing by means of Finn Chambers technique was performed in 5 subjects to induce an acute allergic skin reaction. Noninvasive CM images from normal and eczematous skin were sequentially recorded before and after removal of the Finn Chambers. RESULTS: The epidermis and papillary dermis were clearly seen in high resolution. Retention of nuclei in stratum corneum, epidermal edema with microvesicle formation, and transepidermal migration of inflammatory cells were observed in vivo. Isolated dendritic cells were present in the ACD sites of 2 subjects, with morphology, size, and location consistent with Langerhans cells. Dermal vasodilation was observed as well. CONCLUSION: CM is a useful tool to study ACD and may be able to track Langerhans cell activation

OBJECTIVE: To review the effectiveness of a perioperative management protocol and our experience with a large population of patients with von Willebrand disease (vWD) who require adenotonsillar surgery (T&A). DESIGN: A retrospective review of the medical records of all patients having the diagnosis of vWD who underwent T&A between January 1, 1992, and July 31, 1996. SETTING: A tertiary care, university-based children's hospital. INTERVENTIONS: Patients having a preoperative diagnosis of vWD received a single intravenous dose of desmopressin acetate, 0.3 pg/kg, approximately 20 minutes before the induction of anesthesia. Beginning January 15, 1994, a standard management protocol involving the postoperative administration of fluids and electrolytes was followed. MAIN OUTCOME MEASURES: Operative blood loss and the incidence of postoperative bleeding and of hyponatremia. RESULTS: Of approximately 4800 patients who underwent T&A during the study period, 69 patients had a diagnosis of vWD. All 67 patients identified preoperatively received desmopressin; 2 were identified by postoperative workup as a result of excessive surgical bleeding. Minimal immediate postoperative bleeding was noted in 7 patients (10%), but none required intervention. Delayed bleeding occurred in 9 patients (13%); all were readmitted to the hospital for observation, 4 (6%) requiring operative cauterization. Substantial postoperative hyponatremia occurred in 3 patients, and 1 patient had seizure activity. Symptomatic hyponatremia has been avoided since a protocol of fluid and electrolyte administration was instituted. CONCLUSIONS: Although T&A can be performed safely in patients with vWD, it is not without an increased risk of postoperative hemorrhage. The administration of desmopressin has been reported to reduce the risk of bleeding, but it is not without risk. A protocol for fluid and electrolyte management is recommended