William M. Keane

Expression of the RET/PTC Fusion Gene as a Marker for Papillary Carcinoma in Hashimoto's Thyroiditis†

Hashimotos thyroiditis is an inflammatory disease of the thyroid gland with autoimmune etiology. 1 Patients afflicted with Hashimotos have a higher risk of thyroid malignancies such as papillary thyroid carcinoma. 2 In the present study, we investigated the frequency of papillary thyroid carcinoma specific genes in patients diagnosed with Hashimotos disease. The newly identified oncogenes RET/PTC1 and RET/PTC3 provide useful and specific markers of the early stages of papillary carcinoma as they are highly specific for malignant cells. Using a sensitive and specific reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay, we found messenger RNA(mRNA) expression for the RET/PTC1 and RET/PTC3 oncogenes in 95% of the Hashimotos patients studied. All Hashimotos patients presenting without histopathologic evidence of papillary thyroid cancer showed molecular genetic evidence of cancer. These data suggest that multiple, independent occult tumors exist in these patiens at high frequency.

Daily image guidance with cone-beam computed tomography for head-and-neck cancer intensity-modulated radiotherapy: a prospective study.

PURPOSE To report on a prospective clinical trial of the use of daily kilovoltage cone-beam computed tomography (CBCT) to evaluate the interfraction and residual error motion of patients undergoing intensity-modulated radiotherapy for head-and-neck cancer. METHODS AND MATERIALS Patients were treated with intensity-modulated radiotherapy with an Elekta linear accelerator using a mounted CBCT scanner. CBCT was performed before every treatment, and translational (but not rotational) corrections were performed. At least once per week, a CBCT scan was obtained after intensity-modulated radiotherapy. Variations were measured in the medial-lateral, superoinferior, and anteroposterior dimensions, as well as in the rotation around these axes. RESULTS A total of 28 consecutive patients (1,013 CBCT scans) were studied. The average interfraction shift was 1.4 +/- 1.4, 1.7 +/- 1.9, and 1.8 +/- 2.1 mm in the medial-lateral, superoinferior, and anteroposterior dimensions, respectively. The corresponding average residual error shifts were 0.7 +/- 0.8, 0.9 +/- 0.9, and 0.9 +/- 0.9 mm. These data indicate that in the absence of daily CBCT image-guided radiotherapy, a clinical target volume to planning target volume margin of 3.9, 4.1, and 4.9 mm is needed in the medial-lateral, superoinferior, and anteroposterior dimensions, respectively. With daily CBCT, corresponding margins of 1.6, 2.5, and 1.9 mm should be acceptable. Subgroup analyses showed that larynx cancers and/or intratreatment weight loss indicate a need for slightly larger clinical target volume to planning target volume margins. CONCLUSION The results of our study have shown that image-guided radiotherapy using CBCT for head-and-neck cancer is effective. These data suggest it allows a reduction in the clinical target volume to planning target volume margins by about 50%, which could facilitate future studies of dose escalation and/or improved toxicity reduction. Caution is particularly warranted for cases in which the targets are mobile (e.g., the tongue).

Pretreatment FDG‐PET standardized uptake value as a prognostic factor for outcome in head and neck cancer

We studied the potential prognostic significance of pretreatment 18‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) standardized uptake value (SUV) in squamous cell carcinoma of the head and neck (SCCHN).

Complications of Intubation

Endotracheal intubation with current inert low-pressure, high-volume cuffed tubes is a safe procedure associated with few complications in the vast majority of patients. However, complications related to mechanical difficulties and mucosal injury can occur even under ideal circumstances. Immediate complications are primarily associated with problems during intubation and extubation while early and late complications represent the short- and long-term effects of epithelial trauma.

Amyloidosis of the upper aerodigestive tract

Objectives/Hypothesis To delineate the clinical and pathologic characteristics of upper aerodigestive tract amyloidosis with particular attention to laryngeal amyloidosis.

Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto's thyroiditis.

Objectives Cyclooxygenases (COX) are enzymes that catalyze the conversion of arachidonic acid to prostaglandins. COX‐2, unlike the constitutively expressed COX‐1, is an inducible enzyme upregulated during cell proliferation and inflammation. More recently, COX‐2 has been implicated in the development of numerous types of epithelial cancers. In addition, COX‐2 is highly expressed in several inflammatory diseases. Because of its dual role in inflammation and cancer, we were interested in determining if COX‐2 plays a role in the development of human thyroid carcinoma and Hashimotos thyroiditis, an autoimmune condition frequently associated with thyroid malignancy.

Olfactory neuron-specific expression of NeuroD in mouse and human nasal mucosa.

Abstract. Human olfactory neuroepithelium (OE) is situated within the olfactory cleft of the nasal cavity and has the characteristic property of continually regenerating neurons during the lifetime of the individual. This regenerative ability of OE provides a unique model for neuronal differentiation, but little is known about the structure and biology of human olfactory mucosa. Thus, to better understand neurogenesis in human OE, we studied the expression of olfactory marker protein (OMP), TrkB and NeuroD in human nasal biopsies and autopsy specimens and compared these data with those obtained from normal and regenerating mouse OE. We show that NeuroD and TrkB are coordinately expressed in human OE. Thus, by using these markers we have been able to extend the known boundaries of the human OE to include the inferior middle turbinate. In normal mouse OE, TrkB and OMP expression overlap in cells closest to the superficial layer, but TrkB is expressed more strongly in the lower region of this layer. In contrast, NeuroD expression is more basally restricted in a region just above the globose basal cells. These characteristic expression patterns of OMP, TrkB and NeuroD were also observed in the regenerating mouse OE induced by axotomy. These results support a role of NeuroD and brain-derived neurotrophic factor (BDNF), the preferred ligand for TrkB, in the maintenance of the olfactory neuroepithelium in humans and mice.

Superficial Musculoaponeurotic System Elevation and Fat Graft Reconstruction After Superficial Parotidectomy

Objective/Hypothesis: Elevation of the superficial musculoaponeurotic system (SMAS) with or without fat graft interposition during superficial parotidectomy prevents a concave facial deformity and Freys syndrome.

The Evolving Etiology of Bilateral Vocal Fold Immobility

In the past, bilateral vocal fold immobility (BVFI) occurred most commonly after thyroidectomy. However, no large series documenting the etiology of adult BVFI has been published within the past fifteen years. This study reviews the etiologic patterns of BVFI at our institutions. We compare BVFI from before and after 1980. We also review combined studies of unilateral vocal fold immobility (UVFI) to compare and unilateral versus bilateral etiologic trends. In comparison with previously published series, fewer cases of BVFI present today as a complication of thyroid surgery and more as the result of malignancies and nonsurgical trauma. Unfortunately, BVFI caused by malignancy is not usually an initial sign of local disease, but an ominous sign of recurrence or metastases. In comparing UVFI and BVFI we found that thyroidectomy causes a higher percentage of BVFI than of UVFI. Over one-third of UVFI cases were caused by neoplasm which further underscores the potential seriousness of immobile vocal folds and the need for careful investigation.

Expression of the humanAchaete-Scute 1 gene in olfactory neuroblastoma (esthesioneuroblastoma)

Olfactory neuroblastoma (ONB) is a rare neuronal malignancy of the olfactory mucosal. Markers used in the diagnosis of ONB do not distinguish ONB from other neuronal tumors or tumors with neuroendocrine features thus making the diagnosis of ONB difficult. Using a modified RT-PCR technique, we show that the human homologue of theDrosophila achaete-scute geneHASH1 is expressed in 6 primary and one metastatic ONB specimens, whereas Olfactory Marker Protein (OMP) is not. Previous studies have shown thatHASH1 is expressed in immature olfactory neurons and is required for their development.OMP, whose function is unknown, is expressed exclusively in mature olfactory neurons. Together, these data suggest that ONB is derived from immature olfactory neurons of neuroectodermal origin. Analysis of RNA expression in primary tumor specimens and in an established cell line make this an ideal system to study olfactory growth and differentiation. Furthermore, these studies represent the first molecular genetic analysis of this rare and unusual neuronal tumor.