Frank C. Astor

Characterization of CD44v3-containing isoforms in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease that is only cured 50% of the time. A better understanding of the molecular mechanisms involved in HNSCC progression may lead to earlier detection and improved cure rates. CD44 is a ubiquitous transmembrane glycoprotein comprising a family of alternatively spliced isoforms involved in cell migration and cell proliferation. CD44 isoforms containing the variant 3 (v3) exon include a growth factor binding site and may be involved in tumor progression. To characterize CD44v3-containing isoforms expression in HNSCC we purified RNA from four HNSCC cell lines and performed RTPCR using junction primer strategies followed by gel elecrophoresis. Cloning and sequencing of HNSCC cell line PCR products revealed two isoforms. One of these, CD44v3-10, has been previously described. The other isoform, CD44v3, has not been characterized in HNSCC tissues. To further study this isoform, we purified RNA from 19 HNSCC tissues, 7 normal margin tissues and 5 true normal tissues. Following reversetranscription, we performed quantitative PCR using junction primers specific for CD44v3. Results show that HNSCC tumor tissues expressed mean CD44v3 levels that were elevated 4.5 times more than true normal tissues (p

Posterior Cartilage Graft in Single-Stage Laryngotracheal Reconstruction

PURPOSE: Single-stage laryngotracheal reconstruction (LTR) has gained popularity during the past decade, but few reports discuss posterior grafting. We assessed the indications, treatment, complications, and outcomes for patients who underwent this procedure. METHODS: We reviewed the charts of 120 pediatric patients who underwent LTR at LeBonheur Childrens Medical Center or the University of Mississippi Medical Center between January 1992 and September 2000. We identified and evaluated those who had undergone single-stage anterior plus posterior cartilage rib graft reconstruction during this period. RESULTS: Of 120 patients, 56 had anterior graft procedures, and 46 had anterior plus posterior cartilage rib graft reconstruction. The 46 patients included 26 boys and 20 girls (age range, 18 months to 9 years; follow-up periods, 3 months to 6 years). Twenty-one of 46 had circumferential grade III stenosis, 14 had grade IV stenosis, 4 had bilateral vocal cord paralysis, 4 had posterior glottic and subglottic stenosis, and 3 had laryngeal cleft. Eleven of 46 patients had previous procedures and required revision LTR. All 46 patients underwent single-stage reconstruction with temporary stenting using an endotracheal tube for 10 to 24 days; 4 failed required replacement of the tracheotomy tube, and 8 required reintubation after the first extubation. The overall decannulation success rate was 83% (38 of 46). CONCLUSIONS: LTR is the procedure of choice for the surgical management of subglottic stenosis. Although use of a posterior rib graft is technically demanding and requires extensive experience, good results can be obtained when the guidelines are followed.

Analysis of Short-Term Outcome after Office-Based Laser-Assisted Uvulopalatoplasty

To determine the short-term effectiveness and outcome of office-based laser-assisted uvulopalatoplasty, a prospective statistically controlled study was done at the Department of Otolaryngology, Cleveland Clinic Florida. Thirty-eight consecutive snoring patients underwent a total of 98 laser-assisted uvulopalatoplasties, and data were gathered through examination, interview, and analog scales of snoring, pain, and other morbidity. In addition, a failure analysis was performed. Data were analyzed by descriptive statistics, confidence intervals, and adjusted analysis of variance (p < 0.008). Our results suggest that snoring decreased significantly around each laser-assisted uvulopalatoplasty treatment performed (4 to 8 weeks apart). Postoperative pain diminished after the first two laserassisted uvulopalatoplasty treatments. The only morbidity in the series was the result of significant pain, causing 77% of laser-assisted uvulopalatoplasty failures.

Extraparotid Warthin's Tumor: Clinical Manifestations, Challenges, and Controversies

Extraparotid Warthins tumors continue to challenge the head and neck surgeons diagnostic and therapeutic skills. A series of six extraporotid Warthins tumors are presented to illustrate the need to keep a high index of suspicion for this lesion in the workup of cystic masses involving cervical levels II and III or in the event of a concomitant neck mass and a parotid Warthins tumor. Discussion of the debate surrounding the embryogenesis and histogenesis of extraparotid Warthins tumors follows. Clinical guidelines are suggested for the diagnosis, treatment, and follow-up of patients with extraparotid Warthins tumors.

Prone positioning for head and neck reconstructive surgery.

Certain head and neck surgical cases require the patient to be positioned prone. Such positioning carries with it an attendant subset of risks and complications not otherwise encountered in more traditional supine positioning. Gaining awareness of these risks and complications, and developing proactive positioning strategies, will enable the surgical team to position the patient optimally for the procedure and provide for every consideration of patient safety.

Parotid surgery using Nd:YAG laser contact tips: clinical assessment of perioperative facial nerve function.

OBJECTIVE The objective of this paper is to review 51 consecutive contact Nd:YAG laser parotidectomies to determine perioperative outcomes and complications related to the facial nerve and the use of the laser tips. BACKGROUND DATA Parotid surgery is mostly performed with scalpel or scissors, techniques that may put the facial nerve at risk for injury due to brisk bleeding and imprecise dissection. Even though previous experiences with Nd:YAG lasers in surgery had raised concerns of energy dispersion, the contact sapphire tips used in this series allowed accurate precise dissection and hemostasis, limiting complications. MATERIALS AND METHODS Close facial nerve dissection was done at 8-12 watts, for an average total of 8,000-12,000 joules per case. RESULTS No significant or permanent facial nerve complications resulted from the use of the laser tips, except for expected transient and reversible postoperative ipsilateral marginal mandibular nerve paresis observed in 43% of the patients-less than the generally quoted 50% expected after uneventful lateral lobe parotidectomy. CONCLUSION This review concludes that the contact Nd:YAG laser may offer significant technical and safety advantages, and no direct associated complications in the dissection and preservation of the facial nerve in parotidectomy.

08:18 AM: Frozen-Section Biopsy Analysis for Invasive Fungal Sinusitis

OBJECTIVE: Innovative catheter technology has spawned minimally invasive treatment options for cardiac, vascular, and urologic conditions. Recently, balloon catheters were designed to relieve sinus ostia obstruction (sinuplasty). Safety and feasibility was demonstrated in a small patient cohort. The aims of the present study were to confirm the safety of sinuplasty in a larger cohort, to evaluate the effectiveness of sinuplasty in achieving and maintaining sinus ostia patency, and to gain insight into the ability of sinuplasty to relieve sinus symptoms. METHODS: A prospective, multicenter, nonrandomized evaluation was conducted in 115 patients with chronic sinusitis. Patients for whom endoscopic sinus surgery was recommended were offered sinuplasty. Safety was assessed by the rate of adverse events and patency was determined by endoscopic examination. Sinus symptoms were assessed using the Sino-Nasal Outcome Test (SNOT 20), at baseline, and at follow-up encounters. RESULTS: A total of 348 sinus ostia were dilated in 115 patients without adverse effects. Fifty patients (159 ostia) underwent 12-week follow-up and are reported herein as an interim report. Endoscopic examination confirmed ostia patency in 82.4% (131/159 ostia), nonpatency in 2.5% (4/159 ostia), and 15.1% (24/159 ostia) were indeterminate. SNOT-20 scores showed an improvement over baseline of 1.1 (0.8 considered clinically meaningful). (Twelve and 24-week follow-up data for the entire cohort of 115 patients [348 ostia] is anticipated by June 2005, permitting a final report at the September 2006 AAO-HNSF meeting.) CONCLUSIONS: Balloon catheter technology appears to be a safe and effective treatment option to relieve sinus ostia obstruction.

Differential expression of CD44 isoforms in head and neck squamous cell carcinoma

Abstract Problem: CD44 is a trans-membrane molecule comprising multiple isoforms. These isoforms result from alternative splicing of a variant exon region. Several isoforms occur normally while others, termed CD44 variants (CD44v), are expressed in tumors. Specific isoforms CD44v3–10 and CD44 standard exist in normal keratinocytes. Isoform CD44v3 has been identified in tumor tissue. We hypothesize that total CD44 RNA transcripts are differentially expressed in head and neck squamous cell carcinoma (HNSCC) tissues compared to normal controls and that isoform CD44v3 is overexpressed in tumor tissue. Methods: Five samples of microdissected mucosa from uvulopalatopharyngoplasty patients and 5 samples of HNSCC tissue from various sites were examined. We performed RNA extraction and reverse transcriptase polymerase chain reaction (RT-PCR) using primers that amplify the alternative splicing region followed by gel electrophoresis. We performed quantitative PCR using a junction primer strategy that only amplifies isoform CD44v3 and western blot analysis using an antibody to total CD44. Results: RT-PCR results suggest that at least 3 of 5 tumors and only 1 of 5 normals contain more than 3 CD44 isoforms. The 3 isoforms seen consistently in both normal and tumor tissues correspond to specific isoforms CD44 standard, CD44v3, and CD44v3–10 by base-pair analysis. Quantitative PCR demonstrated that 4 of 5 tumor samples showed greater expression of isoform CD44v3 than all the normal samples. Western blot suggests that there are CD44 isoforms present in tumor that are not present or expressed at low levels in normals. Conclusion: These results support the hypothesis that isoforms of CD44 are differentially expressed in HNSCC compared to normals. We plan to study more tissues at the transcript and protein level and characterize additional specific isoforms using cloning and sequencing. Significance: Understanding CD44 isoform expression in HNSCC tissue compared to normal upper aerodigestive tract mucosa may establish CD44 as a tumor marker. Support: This work was supported by funding from the Flight Attendant Medical Research Institute and the Sylvester Comprehensive Cancer Center.