bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Pathogenesis in Sporadic Head and Neck Paraganglioma
Authors: Bikhazi Paul H. , Messina Louis , Mhatre Anand N. , Goldstein Jayne A. , Lalwani Anil K.
Published: November 2003

Hypothesis Similar to familial tumors, sporadic head and neck paragangliomas are associated with chromosomal deletions at either 11q13 or 11q22‐23.

Background Familial paragangliomas are inherited in an autosomal dominant pattern with genomic imprinting of the maternal allele. Genetic studies of familial paragangliomas have localized the causative genetic defect to two separate loci: 11q13.1 and 11q22‐23. The molecular pathogenesis of sporadic head and neck paragangliomas has not been studied.

Methods Blood and tumor samples from patients with sporadic head and neck paragangliomas were screened for deletions on chromosome 11 using DNA microsatellite markers and polymerase chain reaction. Polymerase chain reaction–amplified alleles from tumor specimens were compared with those from the blood of eight patients. A greater than 50% reduction in band intensity (as determined by densitometric analysis) between blood and tumor sample was indicative of a chromosomal deletion.

Results Three of the eight patients were found to have deletions at chromosome 11q: two at chromosome 11q22‐23 and one at 11q13.

Conclusions Sporadic head and neck paragangliomas are associated with deletions at chromosome 11q13 and 11q22‐23. It is thus likely that sporadic and familial paragangliomas share a similar molecular pathogenesis.
Neurological Consequences of Scuba Diving With Chronic Sinusitis
Authors: Joseph Parell G. , Becker Gary D.
Published: November 2003

Sinus barotrauma from scuba diving is relatively common, usually self‐limiting, and often the result of transient nasal pathology. We describe serious neurological sequelae occurring in two scuba divers who had chronic sinusitis. We suggest guidelines for evaluating and treating divers who have chronic sinusitis. Divers with nasal or sinus pathology should be aware of the potentially serious consequences associated with scuba diving even after endoscopic sinus surgery to correct this condition.
Postnatal Maturation of the Human Endolymphatic Sac
Authors: Ng Matthew
Published: November 2003

Objective/HypothesisThe objective of this study was to trace the postnatal development of the human endolymphatic sac. The endolymphatic sac starts as a pouch‐like structure during the fetal period in the human but later develops into a complex network of tubules in its mature form.

Study DesignObservational study.

MethodsLight microscopic examination of the morphology of the endolymphatic sac in a population of temporal bones.

ResultsExamination of 28 temporal bones from 19 infants and children reveals that endolymphatic sac morphological maturation is usually completed in the first year of life, although it may occur as late as 4 years of age. There was good correlation of maturation levels between sides when pairs of temporal bones were evaluated. Immature pouch‐like endolymphatic sacs may appear as late as 4 years of age.

ConclusionsEndolymphatic sac maturation to its adult tubular form is usually completed by the first year. This finding contrasts with other studies examining the growth of the endolymphatic sac to adult size after birth. Histological evidence suggests that the endolymphatic sac, although not morphologically mature by appearance, may still be participating at some level of functioning.
Interleukin‐1 Receptor Antagonist As an Adjunct in the Treatment of Haemophilus influenzae Otitis Media in the Chinchilla
Authors: Kerschner Joseph E. , Beste David J. , Lynch Jennifer B. , Fox Mary C. , Sue Kehl Karen
Published: November 2003

Objectives This purpose of this study was to investigate the effect of blockade of the inflammatory cytokine pathway on experimentally induced otitis media in the chinchilla model.

Study Design Pilot, randomized placebo‐controlled trial.

Methods Ampicillin‐sensitive Haemophilus influenzae otitis media was induced in 45 adult chinchillas. The animals were randomly assigned to the following treatment groups: 1) transbullar injections (TBI) of interleukin‐1 receptor antagonist (IL‐1ra) and intramuscular ampicillin, 2) TBI of saline and intramuscular ampicillin, 3) TBI of IL‐1ra and intramuscular saline or 4) TBI of saline and intramuscular saline. Blinded investigators measured resolution of otitis media by otomicroscopy, tympanogram, and culture results.

Results Comparisons were made between the treatment groups to assess the ability of IL‐1ra to assist with resolution of otitis media using exact two‐group binomial tests with the StatXact statistical program. The group with TBI of IL‐1ra and intramuscular ampicillin as a treatment demonstrated trends suggesting more rapid resolution of positive cultures and more rapid and complete return to normal results on tympanograms and otomicroscopic findings compared with the group treated with TBI of saline and intramuscular ampicillin. These trends did not achieve statistical significance with the relatively small sample sizes used in this pilot study.

Conclusions This investigation provides further evidence that the inflammatory cytokine cascade plays a significant role in the pathophysiology of otitis media and that modulation of this inflammatory pathway may provide novel and efficacious treatments for otitis media. Further studies with larger groups of animals are warranted to determine whether the trends identified in this pilot study are reproducible and achieve statistical significance.
Vocal Fold Paralysis After Anterior Cervical Spine Surgery: Incidence, Mechanism, and Prevention of Injury
Authors: Kriskovich Mark D. , Apfelbaum Ronald I. , Haller Jeffrey R.
Published: November 2003

Objective Vocal fold paralysis is the most common otolaryngological complication after anterior cervical spine surgery (ACSS). However, the frequency and etiology of this injury are not clearly defined. This study was performed to establish the incidence and mechanism of vocal fold paralysis in ACSS and to determine whether controlling for endotracheal tube/laryngeal wall interactions induced by the cervical retraction system could decrease the rate of paralysis.

Study Design Retrospective review and complementary cadaver dissection.

Methods Data gathered on 900 consecutive patients undergoing ACSS were reviewed for complications and procedural risk factors. After the first 250 cases an intervention consisting of monitoring of endotracheal tube cuff pressure and release of pressure after retractor placement or repositioning was employed. This allowed the endotracheal tube to re‐center within the larynx. In addition, anterior approaches to the cervical spine were performed on fresh, intubated cadavers and studied with videofluoroscopy following retractor placement.

Results Thirty cases of vocal fold paralysis consistent with recurrent laryngeal nerve injury were identified with three patients having permanent paralysis. With this technique temporary paralysis rates decreased from 6.4% to 1.69% (P = .0002). The cadaver studies confirmed that the retractor displaced the larynx against the shaft of the endotracheal tube with impingement on the vulnerable intralaryngeal segment of the recurrent laryngeal nerve.

Conclusion The study results suggest that the most common cause of vocal fold paralysis after anterior cervical spine surgery is compression of the recurrent laryngeal nerve within the endolarynx. Endotracheal tube cuff pressure monitoring and release after retractor placement may prevent injury to the recurrent laryngeal nerve during anterior cervical spine surgery.
Basaloid Squamous Cell Carcinoma of the Head and Neck
Authors: G. Paulino Augusto F. , Singh Bhuvanesh , Shah Jatin P. , Huvos Andrew G.
Published: November 2003

Objective/Hypothesis Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions.

Study Design Retrospective.

Methods H&E‐stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow‐up was obtained for all patients.

Results The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the laryn‐ (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharyn‐ (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow‐up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease.

Conclusion BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age‐matched and stage‐matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high‐stage presentation or to the tumor's high‐grade malignant cytological features.
Workforce Issues for the Academic Otolaryngologist
Authors: Smith Richard V.
Published: November 2003

Background The current medico‐economic environment has led to profound changes in our health care system and questions of physician surplus. These issues have particularly affected the academic health care system, as research funding and departmental support have decreased, and many young otolaryngologists are questioning academic careers because of these uncertainties. The current study was undertaken to assess the workforce environment for the academic otolaryngologist, particularly the young physician.

Methods Surveys were sent to the academic chairmen of all accredited otolaryngology residency programs in the United States, requesting information on faculty appointments—actual and projected—as well as subspecialty appointments and expectations of young faculty.

Results The response rate was 60% (59/98). Faculty additions have been relatively stable from 1994 to 1998, with approximately 37 assistant professor and 5 associate professor positions filled yearly. Faculty additions were the result of departmental expansion in 83% of cases and spanned many subspecialties. The subspecialty positions most frequently added from 1994 to 1998 were generalists (57), head and neck oncologists (53), pediatric otolaryngologists (48), and otologists (39), with generalists filling 15 positions in 1998. Ninety‐three percent of programs anticipate faculty additions in the next 5 years; most will be at the assistant professor level (77%), with 30% of positions for generalists, 20% for head and neck oncologists, and 18% for pediatric otolaryngologists. Faculty expectations are primarily clinical, with research being least important.

Conclusions Academic positions are available for the young otolaryngologist, particularly in the fields of general otolaryngology, head and neck oncology, and pediatric otolaryngology.
Efficacy of Transoral Intraluminal Wallstents for Tracheal Stenosis or Tracheomalacia
Authors: Casiano Roy R. , Numa William A. , Jacobo Nurko Y.
Published: November 2003

Objectives The efficacy and safety of intraluminal Wallstent Endoprosthesis (Boston Scientific/Medi‐Tech, Quincy, MA) placement to restore airway patency in patients with tracheal stenosis or tracheomalacia are unknown.

Study Design Retrospective review in setting of tertiary, referral, and academic center.

Methods A retrospective review of 13 consecutive patients over a 2‐year period who underwent transoral resection of tracheal stenosis and immediate transoral Wallstent placement. One patient had tracheomalacia. All of the patients were considered at high risk for transcervical surgery or had failed prior traditional open procedures.

Results The average patient age was 54.2 years, with nine male and four female patients. All had Cotton/Myer stenoses (grades II to IV) with moderate to severe degrees of inspiratory stridor. Four patients were tracheotomy dependent. The length of stenosis varied from 1 to 4 cm. One patient had a 10‐cm segment of tracheomalacia. At the time of writing, none of the patients has had a problem with significant migration or extrusion and most of the patients have incorporated the stent well without any short‐term obstructive granulation tissue. After a mean follow‐up of 15 months (range, 4–24 mo). 10 of the 12 patients with stenosis (83%) have remained free of any inspiratory noise during breathing. The one patient with tracheomalacia also has remained free of symptoms.

Conclusions Transoral Wallstents appear to be safe and may be a reasonable alternative in the restoration of airway patency in select patients with tracheal stenosis or tracheomalacia.
More Aggressive Behavior of Squamous Cell Carcinoma of the Anterior Tongue in Young Women
Authors: Vargas Hannah , Pitman Karen T. , Johnson Jonas T. , Galati Lisa T.
Published: November 2003

Objective To review the combined experience from two large medical centers in treating young female patients with anterior tongue cancer to determine the clinical course of this unique subset of patients.

Study Design Retrospective study.

Methods Seventeen female patients less than 40 years of age (group A) and 17 older patients, both male and female, greater than 40 years of age (group B) who had treatment for invasive squamous cell carcinoma of the anterior tongue were studied. The charts were reviewed for the clinical staging, treatment, and outcome of each patient. The disease‐free survival and recurrence rates were compared between the two cohorts.

Results The mean disease stage between the groups was II. The survival analysis showed a significant difference between the two groups in recurrences (group A = 65%, group B = 41%;P = .02). Further, of the patients who had recurrence, the young women did so significantly earlier in their disease course than the older patients (group A = 14 mo, group B = 40 mo;P < .05). Although the survival differences did not reach statistical significance (P = .15), the power of the study was low (power = 0.26) resulting in a high‐level type II error.

Conclusion These data suggest that young women with squamous cell carcinoma of the anterior tongue have significantly higher rates of recurrent disease and the interval to recurrence is significantly shorter than in older patients. Further investigation is warranted until a statistically significant cohort is accrued; until that time, these patients warrant an aggressive initial treatment and close surveillance for recurrence.
External Beam Radiation Followed by Planned Neck Dissection and Brachytherapy for Base of Tongue Squamous Cell Carcinoma
Authors: Kaylie David M. , Stevens Kenneth R. , Kang Mathew Y. , Cohen James I. , Wax Mark K. , Andersen Peter E.
Published: November 2003

Background Surgical resection of tongue base cancer can leave the patient with significant functional deficits. Other therapies, such as external beam radiation followed by neck dissection and radiation implants, have shown equal tumor control with good functional outcome.

Methods Between March 1991 and July 1999, 12 patients at Oregon Health Sciences University, the Portland Veterans Administration Medical Center and West Virginia University School of Medicine Hospital were treated with external beam radiation followed by neck dissection and Ir192 implants. Two patients had T1 disease, two had T2, five patients had T3 tumors, and three had T4 tumors. Six had N2a necks, three had N2b necks, and three had N2c. Follow‐up ranged from 13 months to 8 years.

Results After external beam radiation, five patients had complete response and seven had partial response in the neck without complications. One patient underwent a unilateral radical neck dissection, eight had unilateral selective neck dissections involving levels I to IV, and three had dissections involving levels I to III. One of the five patients who had a complete clinical response in the neck had pathologically positive nodes. One patient had a pulmonary embolus that was treated and had no permanent sequelae. There were three complications from brachytherapy. Two patients had soft tissue necrosis at the primary site and one patient had radionecrosis of the mandible. All healed without further therapy. One patient had persistent disease and underwent a partial glossectomy but died of local disease. Distant metastasis developed in two patients. All others show no evidence of disease and are able to eat a normal diet by mouth.

Conclusion This combination of therapies should be considered when treating tongue base cancer.
Glutathione S‐Transferase π in Squamous Cell Carcinoma of the Head and Neck
Authors: Bentz Brandon G. , Kenneth Haines G. , Radosevich James A.
Published: November 2003

Objectives/Hypothesis Oxidative/reductive (redox) DNA damage from radical species such as nitric oxide (NO·) are increasingly being implicated in the development of cancer. Moreover, redox‐protective cellular mechanisms, such as glutathione S‐transferase, may determine cellular susceptibility to this redox‐mediated damage.

Methods Formalin‐fixed, paraffin‐embedded tissue samples of 11 normal oral mucosa, 15 reactive/dysplastic lesions, and 131 head and neck squamous cell carcinomas (HNSCCs) were immunohistochemically stained using a polyclonal antibody against glutathione S‐transferase π (GST‐π). Slides were reviewed in a blinded fashion by the study pathologist (g.k.h.) and intensity was graded, noting the pattern of immunostaining. These staining characteristics were compared with those obtained using monoclonal antibodies against endothelial constitutive nitric oxide synthase (ecNOS) and nitrotyrosine, a marker of NO·'s pathological nitrosylation of proteins on serial sections of the same tissue. Patient charts were reviewed and clinical data collected.

Results The expression of GST‐π was significantly increased in reactive/dysplastic and HNSCC samples compared with normal squamous mucosa (P < .001 for both). Furthermore, among the carcinomas the expression of GST‐π was significantly increased in higher‐grade lesions (P < .02). The expression of GST‐π correlated highly with the expression of ecNOS and nitrotyrosine (P < .0001 for both).

Conclusions These findings demonstrate that GST‐π is upregulated in conjunction with the NO·‐generating ecNOS isoform and implicate GST‐π in protecting HNSCC from the cytotoxic effects of high concentrations of NO· found in the tumor bed.
Therapeutic Efficacy of Th1 and Th2 L‐selectin− CD4+ Tumor‐Reactive T Cells
Authors: To Wyatt C. , Seeley Brook M. , Barthel Steven W. , Shu Suyu
Published: November 2003

Objective To evaluate the cytokine secretion profile and therapeutic efficacy of Th1 CD4+ L‐selectin− tumor‐draining lymph node lymphocytes in the treatment of murine pulmonary metastases.

Study Design Prospective, murine in vivo and in vitro study.

Methods B6 mice were injected bilaterally subcutaneously with MCA 205 sarcoma cells to initiate tumor growth. Eleven days later, tumor‐draining inguinal lymph nodes were harvested. Single‐cell suspensions were prepared and fractionated using magnetically activated cell sorting. Sorted CD4+ L‐selectin− lymphocytes were activated with anti‐CD3 monoclonal antibody for 48 hours either alone to give a Th1 phenotype, or in the presence of interleukin (IL)‐4 and anti‐interferon‐γ (α‐IFN‐γ) monoclonal antibody to elicit a Th2 phenotype. Activated cells were then expanded for 3 days in IL‐2. Resulting cells were used to treat 3‐day pulmonary metastases. Enzyme‐linked immunosorbent assay and intracellular fluorescent‐activated cell‐sorter (FACS) scanning were used to evaluate the cytokine secretion profiles of these cells.

Results Activated and expanded L‐selectin− CD4+ T cells demonstrated a Th1 cytokine profile and excellent antitumor efficacy. In contrast, L‐selectin− CD4+ lymphocytes activated in the presence of IL‐4 and α‐IFN‐γ monoclonal antibody demonstrated a Th2‐like profile and significantly (P < .05) poorer antitumor efficacy.

Conclusions The cytokine environment during the activation of tumor‐draining lymph nodes can influence the therapeutic efficacy of activated L‐selectin−, CD4+ T cells. Cell mediated, Th1‐dependent immunity appears to play an important role in mediating tumor regression. Culture conditions promoting Th2 cells resulted in T cells associated with diminished antitumor efficacy.
Sensorineural and Conductive Hearing Loss Associated With Lateral Semicircular Canal Malformation
Authors: Johnson Jacob , K. Lalwani Anil
Published: November 2003

Objective Lateral semicircular canal (LSCC) malformation is one of the most common radiological inner ear malformations. Traditionally, inner ear malformations are thought to be associated with sensorineural hearing loss (SNHL). Recent experience with patients with LSCC malformation suggested that LSCC malformation may be associated with both SNHL and conductive hearing loss (CHL). The auditory phenotype associated with LSCC malformation is not well delineated. The objective of this study is to define the nature of the hearing loss associated with LSCC malformation.

Study Design Retrospective review

Methods Retrospective review of clinical records, audiological evaluation, and imaging studies.

Results Two patients with unilateral and 13 patients with bilateral LSCC malformation were identified. LSCC malformation was associated with CHL in 14% (4 ears), SNHL in 71% (20 ears), normal hearing in 11% (3 ears) and CHL due to atresia in one ear. Hearing loss varied from mild to profound but did not correlate with the severity of LSCC malformation. In bilateral malformation, the hearing loss was asymmetric in half of the cases. Malformation of the posterior limb of the LSCC was always associated with a large vestibular aqueduct. An absent or rudimentary LSCC was invariably associated with a cochlear abnormality.

Conclusions LSCC malformation, like other inner ear malformations such as large vestibular aqueduct and X‐linked mixed deafness with perilymph gusher, can be associated with CHL, SNHL, or normal hearing. Children with unexplained conductive hearing loss often undergo exploratory surgery to improve hearing. Given that inner ear malformations may be associated with a pure CHL, it is critical that children undergo computed tomography scan of the temporal bone prior to undergoing exploratory surgery.
Obstructive Sleep Apnea Syndrome: A Comparison Between Far‐East Asian and White Men
Authors: Li Kasey K. , Kushida Clete , Powell Nelson B. , Riley Robert W. , Guilleminault Christian
Published: November 2003

Objectives To investigate the possible differences between Far‐East Asian men and white men in obstructive sleep apnea syndrome (OSAS).

Study Design Prospective nonrandomized controlled study.

Methods This study compared consecutive Far‐East Asian men with OSAS (n = 50) with two selected groups of White men with OSAS (n = 50 in each group). One group of white men was controlled for age, respiratory disturbance index (RDI), and minimum oxygenation saturation (LSAT). Another group was controlled for age and body mass index (BMI). Cephalometric analysis was performed on all subjects.

Results The majority of the Far‐East Asian men were found to be nonobese (mean BMI, 26.7 ± 3.8) but had severe OSAS (mean RDI, 55.1 ± 35.1). When controlled for age, RDI, and LSAT, the white men were substantially more obese (mean BMI, 29.7 ± 5.8, P = .0055). When controlled for age and BMI, the white men had less severe illness (RDI, 34.1 ± 17.9, P = .0001). Although the posterior airway space and the distance from the mandibular plane to hyoid bone were less abnormal in the Far‐East Asian men, the cranial base dimensions were significantly decreased.

Conclusions The majority of the Far‐East Asian men in this study were found to be nonobese, despite the presence of severe OSAS. When compared with white men, Far‐East Asian men were less obese but had greater severity of OSAS. There may be differences in obesity and craniofacial anatomy as risk factors in these two groups.
Factors in the Pathogenesis of Tumors of the Sphenoid and Maxillary Sinuses: A Comparative Study
Authors: Reino Anthony J.
Published: November 2003

Objectives/HypothesisTo explain the processes that lead to the development of tumors in the maxillary and sphenoid sinuses.

Study DesignA 32‐year review of the world's literature on neoplasms of these two sinuses and a randomized case‐controlled study comparing the normal mucosal architecture of the maxillary to the sphenoid sinus.

MethodsAnalysis of a 32‐year world literature review reporting series of cases of maxillary and sphenoid sinus tumors. Tumors were classified by histological type and separated into subgroups if an individual incidence rate was reported. Histomorphometry of normal maxillary and sphenoid sinus mucosa was performed in 14 randomly selected patients (10 sphenoid and 4 maxillary specimens). Specimens were fixed in 10% formalin, embedded in paraffin, and stained with periodic acid–Schiff (PAS) and hematoxylin. Histomorphometric analysis was performed with a Zeiss Axioscope light microscope (Carl Zeiss Inc., Thornwood, NY) mounted with a Hamamatsu (Hamamatsu Photonics, Tokyo, Japan) color‐chilled 3 charge coupled device digital camera. The images were captured on a 17‐inch Sony (Sony Corp., Tokyo, Japan) multiscan monitor and analyzed with a Samba 4000 Image Analysis Program (Samba Corp., Los Angeles, CA). Five random areas were selected from strips of epithelium removed from each sinus, and goblet and basal cell measurements were made at magnifications ×100 and ×400.

ResultsThe literature review revealed that the number and variety of tumors in the maxillary sinus are much greater than those in the sphenoid. The incidence of metastatic lesions to each sinus is approximately equal. No recognized pattern of spread from any particular organ system could be determined. On histomorphometric study there were no statistically significant differences between the sinuses in the concentration of goblet cells, basal cells, or seromucinous glands.

ConclusionsFactors involved in the pathogenesis of tumors of the maxillary and sphenoid sinuses include differences in nasal physiology, embryology, morphology, and topography. There are no significant histological differences in the epithelium and submucous glands between the two sinuses to explain the dissimilar formation of neoplasms.
Centrosome Hyperamplification in Head and Neck Squamous Cell Carcinoma: A Potential Phenotypic Marker of Tumor Aggressiveness
Authors: Mark Gustafson L. , Gleich Lyon L. , Fukasawa Kenji , Chadwell Jon , Ann Miller Mary , Stambrook Peter J. , Gluckman Jack L.
Published: November 2003

Objectives/Hypothesis There is currently no single histological or genotypic marker that reliably predicts the biological behavior of head and neck squamous cell carcinoma (HNSCC). While multiple genetic mutations have been investigated, no single genotypic alteration has consistently correlated with tumor aggressiveness. Phenotypic markers may prove more predictive, because they can represent many different genetic alterations. We investigated the frequency of centrosome hyperamplification in HNSCC and examined its usefulness as a marker for tumor recurrence.

Study Design Analysis of archived paraffin blocks using immunohistochemistry.

Methods Eighteen patients who underwent resection of oral cavity squamous cell carcinoma were reviewed. Ten patients had cancers that recurred locally within 1 year of resection, and 8 patients were tumor free at 5 years. The amount of centrosome hyperamplification in the cancer specimens and all surgical margins was graded as follows: 0, none; 1+, rare hyperamplification; 2+, greater than 10% of cells per high‐powered field; and 3+, greater than 20% of cells per high‐powered field.

Results Centrosome hyperamplification was found in 17 of 18 tumors (94%). Grade 2+ or 3+ hyperamplification was found more in cancers that recurred (9 of 10) than in those that did not (3 of 8) and was more prevalent in the histologically normal margins of patients with recurrence (8 of 10) than in those without recurrent cancer (3 of 8).

Conclusions Our results demonstrate the e‐tremely frequent occurrence of centrosome hyperamplification in HNSCC. Centrosome hyperamplification is a phenotypic marker for HNSCC and can reflect multiple genotypic changes. Its presence in histologically normal margins suggests that it may be useful for analysis of primary tumors and tumor margins.
Intranasal Surfactant Aerosol Therapy for Otitis Media With Effusion
Authors: Venkatayan Natarajan , Troublefield Yolanda L. , Connelly Patricia E. , Mautone Alan J. , Chandrasekhar Sujana S.
Published: November 2003

Objective To determine the effect of surfactant alone and with other medications delivered intranasally as a metered dose inhaler (MDI) aerosol on the resolution of e‐perimentally induced otitis media with effusion (OME).

Background Eustachian tube dysfunction is a primary factor in the pathogenesis of OME. Intranasal surfactant via MDI has been shown in this laboratory to reduce passive opening pressure of the eustachian tube in normal gerbils and mice.

Study Design OME was developed in 35 gerbils by transtympanic injection of 10 μg lipopolysaccharide from Klebsiella pneumoniae. Pretreatment otomicroscopy and tympanometry were performed to exclude pre‐existing middle ear disease, and postinfection evaluations were performed on alternate days for a period of 30 days. Five animals received no treatment (control group); four were treated with propellant only (placebo); seven received surfactant alone; eight received surfactant and betamethasone; and six received surfactant with phenylephrine. All medications were sprayed intranasally as an aerosolized MDI and administered daily from postinfection day 2 onward.

Results OME resolved after 16.0 ± 0.44 days (mean ± SD) in controls. There was no difference seen in the placebo or the surfactant with phenylephrine groups. Treatment with surfactant yielded resolution in 10.57 ± 0.37 days; this was reduced to 8.57 ± 0.37 days with surfactant plus betamethasone. These differences are statistically significant. There was no recurrence of OME in any group.

Conclusion This study demonstrates that using an aerosolized MDI surfactant with and without betamethasone decreases the duration of OME in this in vivo gerbil model.
Expression Patterns of p27Kip1 and Ki‐67 in Cholesteatoma Epithelium
Authors: Won Chae Sung , Joon Song Jae , Kyu Suh Han , Hyun Jung Hak , Ho Lim Hyun , Jae Hwang Soon
Published: November 2003

Objectives The cell cycle must be involved in cell proliferation of the epithelium of middle ear cholesteatoma. Cyclins and cyclin‐dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression. Cyclin‐CDK complexes are in turn regulated by the cyclin‐dependent kinase inhibitors (CDKIs), which generally inhibit cell cycle progression. One of the important CDKI members is p27Kip1. The goal of this study is to evaluate the expression of p27Kip1 and Ki‐67, a proliferation marker, in cholesteatoma and in the skin of the external ear canal.

Methods The expressions of p27Kip1 and Ki‐67 in cholesteatoma epithelium (n = 20) and ear canal epithelium (n = 7) were investigated by an immunohistochemical technique.

Results In cholesteatoma epithelium specimens, the expression of p27Kip1 was observed from the parabasal layer to the granular layer, but not in the basal layer. Ki‐67 was expressed dominantly in the basal and parabasal cell layers. Their expressions tend to be increased compared with their expressions in the normal ear canal skin. The expression pattern of the proliferation marker Ki‐67 in the epithelial layers of two groups was inversely related to the expression of p27Kip1.

Conclusions In cholesteatoma, the expressions of CDKI and Ki‐67 were both increased in this study. The ability to inhibit proliferative activity was also increased in the cholesteatoma epithelium. The expression pattern of the proliferation marker Ki‐67 in the epithelial layers was inversely related to the expression of p27Kip1. Not only is the proliferation activity increased, but also the ability to inhibit hyperproliferation is increased in the cholesteatoma epidermis. Despite increased proliferative activity in the cholesteatoma epidermis, epithelial cells still retain the capability to prevent cell cycle arrest by means of p27Kip1.
Aldosterone (Mineralocorticoid) Equivalent to Prednisolone (Glucocorticoid) in Reversing Hearing Loss in MRL/MpJ‐Faslpr Autoimmune Mice
Authors: Trune Dennis R. , Beth Kempton J. , Kessi Monica
Published: November 2003

Hypothesis Although the glucocorticoid prednisone is the standard therapy for autoimmune sensorineural hearing loss, what this hormone does in the ear to restore hearing is not known. MRL/MpJ‐Faslpr autoimmune mice consistently have shown only stria vascularis disease, implying that abnormal ion balances in the endolymph underlie cochlear dysfunction. Previously we have shown that hearing loss in these mice is reversed with prednisolone treatment. This, coupled with the complete lack of cochlear inflammation, suggests that the restoration of hearing with prednisolone is due to its sodium transport function and not to its anti‐inflammatory or immune suppression effects. Therefore the hypothesis of this study was that the mineralocorticoid aldosterone, which only increases sodium transport, would be as effective as prednisolone in reversing autoimmune hearing loss.

Study Design MRL/MpJ‐Faslpr autoimmune mice were treated with either prednisolone or aldosterone to compare steroid effects on auditory brainstem response (ABR) thresholds and stria morphology.

Methods After baseline ABR audiometry, autoimmune mice were given prednisolone (5 mg/kg per day), aldosterone (15 μg/kg per day), or water in their drinking bottles. After 2 months of treatment the ABR thresholds were remeasured, and ears collected for histological examination.

Results The untreated controls showed continued elevation of ABR thresholds and edematous stria. However, thresholds in most steroid mice were improved or unchanged and their stria morphology improved, particularly with aldosterone treatment.

Conclusions Restoration of hearing with steroid treatment is due to increased sodium transport to re‐establish cochlear ionic balances. Aldosterone therapy may offer advantages over prednisone for long‐term management of not only autoimmune hearing loss, but also other forms of nonimmune‐related deafness for which steroids are currently prescribed.
Effects of Adductor Muscle Stimulation on Speech in Abductor Spasmodic Dysphonia
Authors: Bidus Kimberly A. , Thomas Giovana R. , Ludlow Christy L.
Published: November 2003

Objective To determine whether adductor laryngeal muscle stimulation might be a beneficial treatment alternative for abductor spasmodic dysphonia (ABSD).

Study Design Baseline comparisons were made on measures of voiceless consonant and syllable duration between patients with ABSD and normal control subjects, and speech and voice production with and without muscle stimulation were compared within 10 patients with ABSD.

Methods Baseline group comparisons were conducted on measures of syllable and voiceless consonant duration between the patients and the control subjects. Neuromuscular stimulation was applied to the thyroarytenoid or lateral cricoarytenoid muscles in the patients during e‐tended phonation, and measures were made of fundamental frequency and sound pressure level in the stimulated and nonstimulated conditions. Voiceless consonant duration was compared with and without adductor laryngeal muscle stimulation during syllable repetitions and sentences in the patients.

Results Before stimulation, the patients had increased syllable durations in comparison with control subjects (P = .003). Repeated within‐patient comparisons with and without stimulation demonstrated significant (P < .008) reductions in voiceless consonant durations during syllable repetition. The more severely affected patients had the greatest reductions in voiceless consonant duration during sentence production.

Conclusions Adductor muscle stimulation improved speech production in patients with ABSD, and the improvement was greatest in the most severely affected patients. Therefore adductor muscle stimulation has potential for benefiting patients with ABSD.
Cartilage Tissue Engineering Using Thyroid Chondrocytes on a Type I Collagen Matrix
Authors: Wambach Beth A. , Cheung Herman , Josephson Gary D.
Published: November 2003

Objective/Hypothesis Reconstructive procedures of the head and neck often require materials that offer long‐term structural support. A problem that many surgeons have encountered is identifying a material that offers this support without rejection of the implanted material. This has led many surgeons to prefer autologous cartilage. However, autologous cartilage is of limited supply. Cartilage tissue engineering has become a new modality that allows investigators to harvest a small piece of cartilage and extract its chondrocytes for expansion in culture. These chondrocytes are applied to a matrix that will act as a scaffold and allow for cartilage growth. Finding a compatible matrix seems to be the limiting step in the progress of this research. We describe a new approach of tissue creation using bovine collagen matrices as templates onto which cells are seeded.

Study Design Laboratory research.

Methods Chondrocytes obtained from thyroid cartilage of dogs were seeded onto bovine collagen type I matrices and grown in vitro. Chondrocyte seeded matrices were evaluated histologically.

Results Thyroid chondrocytes expressed themselves phenotypically by producing type II collagen in the presence of this type I collagen matrix.

Conclusions This study offers the preliminary findings on an exciting new type of matrix worth exploring in the ability to successfully engineer cartilage.
Histological Study of Injected Autologous Fascia in the Paralyzed Canine Vocal Fold
Authors: Rodgers Bret J. , Abdul‐Karim Fadi W. , Strauss Melvin
Published: November 2003

Objective Several methods have been used for the treatment of the unilateral paralyzed vocal fold. Teflon injections have been used e‐tensively but not without complications. The ideal substance for injection is yet to be determined. Injected autologous fascia has been reported as a means of achieving glottic closure. In review of the literature, there are no long‐term results described using autologous fascia in this way. The purpose of this study was to e‐amine the histological changes of the laryn‐ after injection of autologous fascia into a paralyzed vocal fold.

Study Design A prospective study with the contralateral side of the laryn‐ used as the control.

Methods Si‐ adult dogs underwent severing of one of their recurrent laryngeal nerves. After the vocal folds were confirmed to be paralyzed by direct laryngoscopy, fascia lata that was harvested from the animal was minced and injected into the paralyzed vocal fold. The dogs were then killed at intervals ranging from 3 to 12 months and their larynges reviewed histologically.

Results The larynges revealed muscle atrophy of the vocal fold, which is consistent with denervation, but there was no evidence of persistent fascia. In addition, there was no evidence of reaction to the injected fascia. Special stains for collagen were also performed which showed no significant change from the non‐injected vocal fold.

Conclusion From this model, it is concluded that injected autologous minced fascia is not a good short‐ or long‐term substance for vocal fold augmentation. Further study is warranted to confirm this observation.
The Role of Fiberoptic Nasopharyngoscopy in the Management of the Acute Airway in Angioneurotic Edema
Authors: Bentsianov Boris L. , Parhiscar Afshin , Azer Marie , Har‐El Gady
Published: November 2003

Background Angioneurotic edema of the upper aerodigestive tract (AEUAT) often challenges the otolaryngologist with the decision of surgical intervention versus observation.

Objective To develop a logical approach to the evaluation and management of the airway in patients with AEUAT, emphasizing fiberoptic examination (FOE) findings.

Methods A computer‐based retrospective review of all patients diagnosed with AEUAT was performed. The charts were reviewed for demographics, etiology, medical history, presentation, physical examination, imaging studies, intervention, and outcome. Findings on FOE as well as other covariants were statistically compared.

Results Seventy patients with AEUAT were identified. The etiologies consisted of 24 cases of angiotensin converting enzyme inhibitor use (33%), 10 allergic reactions (17%), 1 hereditary (1.5%), and 35 idiopathic cases (48%). Fourteen patients underwent airway intervention, including 6 tracheotomies and 8 intubations. Of the 14 patients, 5 underwent emergent intervention before fiberoptic examination, 4 had laryngeal edema only, and 5 had both laryngeal and base of tongue edema. No patients with both laryngeal and base of tongue edema were observed. The remaining 52 patients were observed in a monitored setting and required no subsequent intervention.

Conclusion FOE is an invaluable tool in the assessment of the compromised airway in patients with angioneurotic edema. Laryngeal edema alone is an ominous physical finding. When laryngeal and pharyngeal edema are present together, the physician should consider immediate intervention. Our findings indicate that symptoms, including stridor, hoarseness, and dysphagia, do correlate with disease severity; however, they must be confirmed with fiberoptic visualization. Although sound clinical judgment should always be exercised, we present our results in the management of the acute airway in angioneurotic edema.
Lung Cancer After Head and Neck Cancer: Role of Chest Radiography
Authors: Shah Shefali I. , Applebaum Edward L.
Published: November 2003

Objective To e‐amine whether screening chest radiographs lead to significantly longer life span in patients found to have pulmonary lesions than in those in whom lung cancer was detected after symptoms developed.

Study Design A retrospective study.

Material and Methods Charts of 1086 patients with squamous cell cancer of the head and neck treated for cure from January 1, 1974, to December 31, 1998, were analyzed.

Results Pulmonary cancer developed in 62 patients. In 41 patients pulmonary malignancy was found because of patient symptoms. In 21 patients lung cancer was detected by routine annual chest radiography. Seventy‐five percent of lung cancers were detected within 3 years of initial treatment of the head and neck cancer.

Conclusion Chest radiography is a poor screening tool, because it failed to find pulmonary lesions in more than 65% (41/62) of patients who were later found to have pulmonary cancer. Survival rate did not differ between patients in whom pulmonary cancer was found by screening chest radiography and those in whom symptoms prompted evaluation (P = .48). Using current treatment protocols, routine yearly chest radiography did not improve survival in patients with head and neck cancer. However, there maybe new therapeutic regimens under investigation that would benefit these patients if their lung cancers were found in early stages of disease. Future directives must include the establishment of an effective follow‐up protocol for the early detection of lung malignancies in these patients.
The Free Vascularized Flap and the Flap Plate Options: Comparative Results of Reconstruction of Lateral Mandibular Defects
Authors: Shpitzer Thomas , Gullane Patrick J. , Neligan Peter C. , Irish Jonathan C. , Freeman Jeremy E. , Van den Brekel Michiel , Gur Eyal
Published: November 2003

Objectives/Hypothesis Reconstruction of the mandible and oral cavity after segmental resection is a challenging surgical problem. Although osteocutaneous free flaps are generally accepted to be optimal for reconstruction of anterior defects, the need for bony reconstruction for a pure lateral mandibular defect remains controversial.

Study Design A retrospective study.

Methods A retrospective comparative study of short‐ and long‐term outcomes of three different reconstruction techniques for lateral defects was performed. In total, 57 patients were included, of whom 27 had a plate and pedicled pectoralis major myocutaneous flap (PMMF group), 16 had a plate and free radial forearm flap (FRFF group), and 14 had an osteocutaneous free flap. Functionality, flap failure, and complications were scored.

Results Plates had to be removed in 7 of the 27 patients in the PMMF group and 2 of the 16 in the FRFF group; none of the 14 osteocutaneous free flaps failed. The difference was of borderline statistical significance (P = .055). Long‐term functional outcome revealed no statistically significant difference in oral deglutition (P = .76) or in facial contour (P = .36). Oral continence was significantly better in patients in the FRFF group (88%) as compared with the PMMF group (52%) or the osteocutaneous free flap group (43%) (P = .02). On the other hand, the results for speech favored the osteocutaneous free flap group; 13 of 14 patients (92.9%) had a normal score compared with 12 of 16 patients (75%) in the FRFF group and 17 of 27 (63%) in the PMMF group. However, this represented a borderline statistically significant result (P = .06).

Conclusions For lateral mandibular defects, the osteocutaneous free flap is reliable and durable in the long term. However, in a selected group of patients either of the two flap‐plate options is a viable reconstructive option.
Prognostic Value of Lymph Node Involvement in Oral Cancers: A Study of 137 Cases
Authors: Tankéré Frédéric , Camproux Anne , Barry Béatrix , Guedon Charles , Depondt Joël , Gehanno Pierre
Published: November 2003

Objective The aim of this study was to assess the prognostic value of lymph node involvement in patients with squamous cell carcinoma of the oral cavity.

Study Design Retrospective study of 137 patients with T4 squamous cell carcinoma of the oral cavity treated by surgery and radiotherapy (84 N0, 23 N1, 16 N2, 14 N3). Twenty‐three patients in the N0 group had a history of surgery or radiotherapy. One hundred fourteen patients underwent limited or radical neck dissection unilaterally or bilaterally.

Methods The histological charts were reviewed and correlated with preoperative lymph node clinical stage. The local failure rate and the overall survival curves were calculated with respect to clinical and histological stages. The causes of death were analyzed.

Results No evidence of lymph node metastasis was found in 47.4% of cases (54 of 114 patients). Among the node‐positive (N+) patients, 39 had rupture of the lymph node capsule (R+). In the N0 group, 27.8% of patients were N+. Regional control rates after surgery and radiotherapy were 95% at 1 year and 85.4% at 5 years. The local failure rates were 6% in N0, 8.7% in N1, 31.2% in N2, 51.7% in N3, 9% in node‐negative (N−), and 29% in N+R+ patients. The overall survival rates at 3 and 5 years were, respectively, 44.7% and 34.8% in the N0 group, 37.7% and 37.7% (same rate at 3 and 5 years) in the N1 group, and 31.2% and 15.8% in the N2 group. None of the patients in the N3 group survived beyond 2 years. The overall survival rates at 5 years were 42.8% and 17.5% in the N− and N+ groups, respectively.

Conclusions In patients with locally advanced tumors (T4), clinical nodal status and histological nodal invasion were key prognostic factors. The presence of occult metastases in the N0 group justifies routine neck dissection.