David R. Edelstein

Inhibition of Cyclooxygenase-2 Expression: An Approach to Preventing Head and Neck Cancer

ABSTRACT Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX‐2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX‐2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)‐mediated activation of COX‐2 expression. Levels of COX‐2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100‐fold increase in amounts of COX‐2 mRNA was detected in HNSCC. By immunoblot analysis, COX‐2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF‐mediated induction of COX‐2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX‐2 mRNA, COX‐2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX‐2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX‐2 expression. Combining a retinoid with a selective COX‐2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.

Abnormally large frontal sinus. II. Nomenclature, pathology, and symptoms.

Based on a review of the literature and analysis of six new cases, three categories of enlarged, aerated sinuses are defined, namely: hypersinus, pneumosinus dilatans, and pneumocele. The information gained by our study of the area variation of the frontal sinuses in a normal population (part I of this paper) was utilized to define the term hypersinus. In this condition there is generalized enlargement of the sinus beyond the upper limit of normal in an asymptomatic patient. The principal difference between pneumosinus dilatans and a pneumocele is the presence of bony thinning or erosion in the latter entity. The clinical findings and the possible etiologies of these conditions are discussed.

Aging of the normal nose in adults.

Like other organs, the nose changes as the body ages. A review of the literature reveals a basic understanding of the aging process in the nose but a paucity of documentation and few organized studies. This study was designed to identify systematically the age‐related changes in the normal, nondiseased adult nose.

Changes in nasal epithelium in patients with severe chronic sinusitis: A clinicopathologic and electron microscopic study†

Objective: Defective ciliary ultrastructure and impaired mucociliary clearance play an important role in the development of respiratory disease and sinusitis. Changes in the ciliary ultrastructure of the sinonasal epithelium have been documented in patients with primary ciliary dyskinesia. However, secondary ciliary dyskinesias and epithelial cytopathologic changes have been underappreciated as a consequence of respiratory dysfunction and chronic sinusitis. Study Design: Thirty‐two patients with severe chronic sinusitis were evaluated for ciliary and epithelial abnormalities. Materials and Methods: Fourteen patients (44%) were children who underwent full allergy, sweat, and immunologic workups. Eighteen patients (56%) were adults who had severe refractory sinusitis and had failed previous sinus surgery. All patients underwent nasal epithelium biopsies of the middle turbinate and evaluation by light and transmission electron microscopy. Results: Ciliated cells were found in 23 patients (72%) with 9 patients (28%) having no cilia. Foci of normal ciliated epithelium were found in only 19% of the patients, often in epithelial invaginations. Variable numbers (usually a minor population) of cilia in 20 cases (87%) exhibited ultrastructural defects including compound cilia and microtubule and dynein arm defects. All of the patients showed variable loss of differentiated epithelial cells ranging from denuded epithelium to basal cell hyperplasia often associated with squamous metaplasia, secondary to chronic sinonasal disease. The lamina propria was often edematous with dilated capillaries, plasma cells, lymphocytes, and hyperplastic seromucous glands. Conclusions: This study demonstrates that ciliary dyskinesias are primarily the result rather than the cause of chronic sinusitis. Patients with chronic sinusitis of uncertain origin exhibit a prominent loss of differentiated epithelial cells, as well as ciliary defects, most of which are likely to be secondary to the chronic disease process. These changes slow down mucociliary clearance and lead to a vicious cycle leading to chronicity.

Management of osteomas of the paranasal sinuses.

Craniofacial osteomas are benign tumors of the skull base, often involving the paranasal sinuses. The frontal sinus is the most common site of involvement, followed by the ethmoid, maxillary, and sphenoid sinuses, respectively. The growth rate is very slow, and it may take many years for osteomas to become clinically apparent. The origin of these tumors has been ascribed to embryologic tissue maldevelopment, trauma, or infection. The tumors are hard and lobulated with an ivorylike appearance, often mixed with a coarse granular component. The bone is compact or cancellous, with vascular or connective tissue components. The complications of osteoma growth are obstruction of sinus ostia, extension into adjacent bones and the intracranial cavity, and displacement of anatomic structures. Management of uncomplicated sinus osteomas is controversial, since surgery involves serious potential risks. When surgery is performed, these tumors can be successfully managed via endoscopic, open, or combined techniques. This article reviews the clinical findings, diagnostic studies, and treatment of 16 patients with paranasal osteomas. The indications for surgical intervention are discussed.

Sepragel Sinus (Hylan B) as a Postsurgical Dressing for Endoscopic Sinus Surgery

OBJECTIVE: To assess the safety and efficacy of Sepragel sinus, a hylan B gel (cross-linked hyaluronic acid molecule), when used as a postoperative dressing after endoscopic sinus surgery as a facilitator of healing and a preventative for scarring and stenosis. STUDY DESIGN: Ten patients undergoing bilateral endoscopic ethmoidectomy in an outpatient specialty hospital operating room underwent complete filling of a randomly selected right or left ethmoidectomy cavity with Sepragel sinus. Outcome measures were synechiae, middle meatal stenosis, mucosal status, mucosal regeneration, transparency of Sepragel sinus, and subjective pain and congestion. RESULTS: Sepragel sinus significantly improved all outcome measures by week 2 and remained statistically significant for reduction of synechiae and stenosis. CONCLUSION: Sepragel sinus is useful as a space-occupying gel stent to separate sinus mucosal surfaces. The data strongly support the superiority of Sepragel sinus over no treatment in the control of postethmoidectomy synechiae and middle meatal stenosis, as well as early improvement in mucosal healing and postoperative pain. SIGNIFICANCE: Because of its biocompatibility, lack of inflammatory response, transparency, and ability to fill any complex volume, Sepragel sinus offers distinct advantages over currently used stenting materials.

Green tea regulates cell cycle progression in oral leukoplakia.

A complete in vitro multi‐stage carcinogenesis model for oral cancer was developed to examine chemopreventive strategies. In the present study, the effects of EGCG [(−)‐epigallocatechin‐3‐gallate], the major constituent of green tea, is being examined to understand mechanisms of action.

Cholesteatoma in the Pediatric Age Group

The diagnosis and management of cholesteatoma in children remains controversial. In the past 15 years, the senior author (S.C.P.) has treated 320 patients with cholesteatoma. Patients 18 years and younger composed 40% (125) of the overall group and are the basis for this report. The patient data were compiled using the history, physical examination, audiograms, radiographs, patient questionnaires, surgical findings, and postoperative observations. The surgical treatment selected was determined by the extent of disease, the configuration of the mastoid, and a clinical assessment of eustachian tube function. A middle ear tympanotomy approach was used in 17% of the patients, a canal wall up procedure in 31 %, and a canal wall down procedure in 52.3 %. The average clinical follow-up was 3.9 years, with the range being from 3 months to 13.5 years. Hearing was maintained or slightly improved in a majority of cases. Residual disease occurred in 8 % of patients, and recurrent disease in only 3 %.

Management of labyrinthine fistulas caused by cholesteatoma

The surgical management of labyrinthine fistulas caused by cholesteatoma remains controversial. Forty cases (41 ears) of labyrinthine fistulas were reviewed. This represented 10% of our total series of cholesteatomas in adults and children (426 ears). Clinical presentation, extent of disease, results of fistula testing and audiometric studies, and radiographic findings were analyzed. A canal wall-down procedure was performed in all but one patient. Generally an attempt was made to completely remove the cholesteatoma, to graft the fistulous area, and to reconstruct the middle ear mechanism in one stage. The matrix was preserved in patients with large fistulas where the involved ear was the only hearing one, when the matrix was adherent to the underlying optic duct, and in selected elderly persons. Long-term followup did not reveal a significant difference in hearing, degree of vertigo, or incidence of recidivism when those patients in whom the matrix was removed were compared with those in whom the matrix was preserved. The importance of recognizing the presence of a labyrinthine fistula preoperatively is stressed, along with the need to be prepared for an unexpected fistula. Operative management is described.

Characteristics and outcomes of malpractice claims after tonsillectomy

OBJECTIVE: To characterize the background and outcomes of tonsillectomy malpractice claims. METHODS: Review of 69 New York State insurance claims (Part I) and 87 national court trials (Part II) alleging injury after tonsillectomy. RESULTS: Part I. New York State insurance cases were most commonly discontinued (44%) or settled (42%) before trial. Compensations with a settlement or verdict were made in 48 percent of cases. Part II. Death or major injury occurred in 52 percent of insurance cases, with a mean award of