Design  Immunohistochemical analysis of thyroid neoplasms, including FA (n = 62), FTC (n = 62), and follicular variant of papillary thyroid carcinoma (n = 58), using tissue microarrays. We evaluated antibodies galectin-3, autotaxin, intestinal trefoil factor 3 (TFF3), extracellular matrix metalloproteinase inducer (EMMPRIN), and growth arrest and DNA damage-inducible protein 153 (GADD153). We analyzed data for quantitative differences in IHC intensity and the percentage of positive cells between FAs and combined follicular carcinomas. Sensitivity and specificity analysis are reported, along with a dual-protein clinical algorithm.

Setting  Academic tertiary care center.

Patients  Adults with known follicular and papillary thyroid lesions that were surgically resected during the past 15 years.

Main Outcome Measures  Sensitivity and specificity of individual and combined antibodies for detecting benign from malignant lesions.

Results  Quantitative analysis showed IHC validation of the gene expression differences noted in previously published microarray reports. A significantly higher percentage of FTC cells stained with galectin-3, EMMPRIN, and GADD153. Galectin-3 and EMMPRIN also showed a significantly higher intensity of staining in FTC cells. Compared with malignant lesions, TFF3 stained a greater cell percentage in FAs. Galectin-3 (sensitivity, 0.72; specificity, 0.62) and EMMPRIN (sensitivity, 0.63; specificity, 0.49) had the most promising diagnostic potential with a dual-protein sensitivity of 0.80 and specificity of 0.70. Autotaxin and GADD153 had overall higher sensitivities (0.88 and 0.82, respectively) but very poor specificities (0.02 and 0.21, respectively).

Conclusions  Protein expression data validate the pooled gene expression results that differentiate FTC from FA. Our results show promise for multiple-protein IHC analysis algorithms and their diagnostic ability. Future studies should focus on clinical translation of these molecular differences for the diagnosis of follicular thyroid neoplasms.

Methods  A retrospective medical record review of 10 patients who underwent reconstruction with an occipital rotational flap after auriculectomy or lateral temporal bone resection. Patient and operative variables included age, preoperative ASA (American Society of Anesthesiologists) classification, operative time, total length of hospital stay, and use of preoperative and postoperative radiotherapy. Patient demographic characteristics and medical comorbidities were also recorded. Clinical outcomes included medical complications, minor and major wound complications, and donor site complications.

Results  Patients' mean age was 73.9 years, and mean ASA classification was 2.8. The mean operative time was 8.1 hours, and the mean length of hospital stay was 5.3 days. Three patients received preoperative radiotherapy, and 7 received postoperative radiotherapy. Two patients developed postoperative medical complications, 2 developed minor wound breakdown, and 1 developed a donor site complication.

Conclusion  The occipital flap method is reliable and should be considered as an option for reconstruction after lateral temporal bone resection in select patients.

Design  Review of patient medical records and microscopic slides of all tumor tissues. The histopathologic features for each tumor and the demographic, clinical, treatment, and follow-up information were recorded for each patient. Also, a comparison with previously reported series was performed.

Setting  The University of Texas M. D. Anderson Cancer Center.

Patients  Ten men ranging in age from 35 to 69 years (mean age, 53 years) were included in the study. They all experienced a short course of symptoms, with an average duration of 3.5 months, and 9 presented with nasal obstruction and epistaxis. Nine patients were treated with both surgery and irradiation.

Results  Histologically, the tumors showed primitive neuroepithelial elements and various malignant epithelial and mesenchymal components. Six patients had no evidence of disease by the end of follow-up, which ranged from 72 to 372 months. Three patients died of disease, and 1 patient was lost to follow-up.

Conclusion  Sinonasal teratocarcinosarcoma of the head and neck is a histologically and biologically heterogeneous malignant neoplasm that is best managed with surgery and postoperative radiotherapy.

Design  Prospective study.

Setting  University hospital.

Patients  Thirty-six patients undergoing primary thyroidectomy because of thyroid disease.

Main Outcome Measures  The effect of thyroidectomy on voice was examined by recording the voices of the patients before and 1 week after thyroidectomy. The Multi-Dimensional Voice Program was used for capturing and analyzing the voice samples.

Results  On postoperative examination of objective voice changes, thyroidectomy had no multivariate effect on the combination of voice parameters. Patient sex, type of surgery, and surgeon experience had no effect on the combination of voice parameters before and after thyroidectomy. Regardless of within-patient factors (type of surgery, patient sex, and surgeon experience), 4 acoustic parameters (highest fundamental frequency, standard deviation of average fundamental frequency, phonatory average fundamental frequency range in semitones, and degree of subharmonics) significantly decreased after thyroidectomy (P < .05). Although they tended to be worse, none of the acoustic parameters showed significant changes in male patients. However, significant changes in some of the acoustic parameters of female patients were observed. Highest fundamental frequency, standard deviation of average fundamental frequency, phonatory average fundamental frequency range in semitones, absolute jitter, relative average perturbation, pitch perturbation quotient, shimmer in decibels, percentage of shimmer, amplitude perturbation quotient, noise to harmonic ratio, and degree of subharmonics values were all lower in female patients after thyroidectomy (P < .05).

Conclusions  Voice changes may occur after thyroidectomy without any evident laryngeal injury, and deterioration and amelioration of acoustic parameters can be observed to occur differently among male and female patients. Preoperative and postoperative objective voice analyses may be helpful in documenting voice changes.

Design  Validation study.

Setting  Academic research.

Patients  Three hundred twenty-one patients older than 70 years with head and neck cancer in a tertiary cancer center. Comorbidity was measured using the ACE-27, WUHNCI, and National Cancer Institute (NCI) comorbidity index.

Main Outcome Measure  Five-year overall survival.

Results  Five-year overall and cancer-specific survival, respectively, were as follows: Using the WUHNCI, 52.2% and 62.9% for a score of 0; 25.1% and 41.7% for a score of 1; 39.3% and 64.9% for a score of 2; and 19.5% and 45.0% for a score of 3 or higher. Using the ACE-27, 54.4% and 61.7% for a score of 0 (no comorbidity); 46.8% and 61.7% for a score of 1 (mild comorbidity); 31.7% and 51.6% for a score of 2 (moderate comorbidity); and 13.8% and 43.7% for a score of 3 (severe comorbidity). The C statistics were 0.641 for the NCI comorbidity index, 0.656 for the ACE-27, and 0.686 for the WUHNCI.

Conclusions  The WUHNCI did not demonstrate good discriminative power compared with the ACE-27 in a cohort of older patients. To be widely used, instruments developed to measure comorbidities must be reliable in any population. We believe that the ACE-27 is still the best index to assess comorbidities and that it should be used in studies evaluating the prognostic effect of comorbidities.

Design  Squamous cell carcinoma VII is a poorly immunogenic murine SCC tumor in C3H/HEN (H-2^K) mice. Subdermal tumors were established by inoculation in the mid abdomen of mice. Tumor diameters were measured with a Vernier caliper and used as an indication of treatment efficacy. Survival studies were performed on mice with 3-day pulmonary metastasis or subdermal tumors. Dendritic cells were generated from bone marrow and cultured for 8 days. Dendritic cells were harvested and mixed with cultured tumor cells in a 1:1 ratio. Cell fusion was achieved by exposing the cell mixture to an alternate electrical current to bring cells into alignment and close together, followed by a short direct electrical current pulse.

Subjects  Female C3H/HEN mice aged 8 to 12 weeks.

Interventions  Mice with 3-day established SCCVII tumors were vaccinated by inguinal intranodal injection of fusion cells (0.3 x 10⁶ per side). To support the development of antitumor immunity, mice were given adjuvant injections intraperitoneally. Anti-OX40R monoclonal antibodies or interleukin 12 were used. Treatment groups included no treatment, anti-OX40R monoclonal antibodies or adjuvant IL-12 alone, fusion cells alone, and fusion cells with adjuvant treatment.

Main Outcome Measures  Tumor size and overall survival.

Results  Mice treated with adjuvant treatment or fusion cells alone did not show a statistical difference in tumor growth when compared with controls. In contrast, fusion cells with adjuvant treatment demonstrated a significant decrease in tumor size when compared with nontreated mice (P < .001). Treatment with fusion cells also resulted in increased survival in the pulmonary metastasis and subdermal tumor models.

Conclusion  Immunotherapy with fused dendritic-tumor cell hybrids can significantly affect 3-day established sSCC VII tumor growth.

Design  In vitro study.

Subjects  Strains of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus milleri, Aspergillus flavus, and Aspergillus fumigatus.

Interventions  Bacterial and fungal strains were cultured with 0.1% dexamethasone with and without a low (0.1%) or high (1%) concentration of NCT. The killing effects of dexamethasone, NCT, and the combination were monitored.

Results  Dexamethasone killed S milleri and A flavus after incubation times of 24 to 48 hours. The low concentration of NCT caused a 90% reduction of S aureus and P aeruginosa within 30 minutes and 99.9% reduction within 50 minutes. The high concentration of NCT reduced viable counts of S aureus and P aeruginosa to the detection limit within 10 minutes. The low-concentration combination (0.1% dexamethasone and 0.1% NCT) showed significant (P < .01) synergistic killing of S aureus with 2- to 3-fold shorter killing times. The high-concentration combination (0.1% dexamethasone and 1% NCT) demonstrated more rapid killing than NCT alone in both S aureus and P aeruginosa.

Conclusions  With short and intermediate exposure times, the combination of dexamethasone and NCT showed significantly stronger antimicrobial effects than treatment with NCT alone. Significant killing of S milleri, A flavus, and A fumigatus was observed after extended exposure to dexamethasone. The combined application of dexamethasone and NCT might be a promising therapeutic option, producing high efficacy with low side effects.

Design  Prospective, before-after trial.

Setting  Outpatient clinic of a university clinic for otorhinolaryngology.

Patients  A total of 20 patients with olfactory loss participated in the study. The duration of olfactory deficits ranged from 3 months to 6 years.

Main Outcome Measures  Olfactory function was assessed for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. Olfactory bulb volume was determined using magnetic resonance imaging.

Results  In initially hyposmic patients (n = 13), changes in OB volume were found to correlate with odor threshold changes (r = 0.82; P = .001); no such correlation was found for odor discrimination or odor identification.

Conclusion  As demonstrated in a longitudinal study for the first time to our knowledge, the human OB is a highly plastic structure that responds to individual changes in olfactory status.

Design  Self-reported survey.

Setting  Pediatric tertiary care hospital.

Participants  Consecutive sample of otolaryngology residents and 1 fellow during the 2006-2007 academic year.

Interventions  Foreign body aspiration and ingestion were simulated in a high-fidelity, computer-assisted infant simulation mannequin. Avoidance of complications and successful removal required teamwork and responsiveness to the mannequin's physiologic characteristics in addition to dexterity with instruments.

Main Outcome Measures  Postcourse 5-point Likert scale and subjective evaluation of perceived realism reported by participants.

Results  Participant response was generally positive. Ratings were highest for training cognitive and psychomotor endoscopy skills, preventing and managing complications, and facilitating team process. Overall realism and appropriate "feel" showed opportunity for improvement.

Conclusion  Pediatric otolaryngology trainees perceive that high-fidelity patient simulation facilitates acquisition of aerodigestive endoscopy skills, especially in training cognitive and psychomotor endoscopy skills, preventing and managing complications, and facilitating team process.

Design  Quantitative reverse transcription–polymerase chain reaction (RT-PCR) analysis.

Setting  Academic research.

Participants  Primary fibroblast lines were established from human nasal polyp biopsy tissue specimens (n = 5) removed at polypectomy.

Main Outcome Measures  The expression of TARC messenger RNA (mRNA) was evaluated by real-time RT-PCR. The amount of TARC in the supernatants was measured by enzyme-linked immunosorbent assay.

Results  Combined stimulation with interleukin 4 (IL-4) and tumor necrosis factor (TNF-) or with poly IC and IL-4 induced TARC production. Combined exposure of cells to poly IC, IL-4, and TNF- resulted in substantial amounts of TARC release into the culture medium. Quantitative RT-PCR analysis revealed that simultaneous stimulation with those 3 compounds induced a tremendous increase in the amount of TARC mRNA in the nasal polyp fibroblasts.

Conclusion  Nasal polyp fibroblasts contribute to T_H2 cell infiltration and RNA virus–induced exacerbation of T_H2-type airway inflammatory conditions such as allergic chronic sinusitis.

Design  A fresh porcine trachea divided longitudinally and affixed to a linear translation stage was used to simulate 20 tracheal diameters (18.3-30.3 mm). Tungsten-halogen light was dispersed across the luminal surface by a diffraction grating. Determination of the wavelength of diffusely reflected light of peak intensity by spectrograph analysis then allowed for the calculation of an optical distance for each simulated tracheal diameter. The criterion standard was the distance as measured by the micrometer on the translation stage. Intraclass correlation (ICC) and Bland-Altman regression analysis (BARA) were performed between the optical and micrometer measurements.

Subject  Trachea from a newly exsanguinated pig.

Results  The ICC showed high correlation (0.994; 95% confidence interval [CI], 0.9860.998) (P < .001); BARA showed a small mean difference between the optical and micrometer measurements (0.052 mm; 95% CI, –0.867 to 0.762 mm) and no significant trend in bias for varying diameters (r = 0.581; 95% CI, 0.187-0.814) (P = .07).

Conclusions  The determination of airway diameter by means of the reflection of nonionizing radiation from the luminal surface correlates closely to actual diameter as measured by a micrometer. This bench model may be used to develop a fiberoptic intraluminal probe capable of accurately profiling airway luminal diameter and shape during flexible or rigid bronchoscopy.

Design  Observer-blinded study.

Setting  University hospital research unit.

Participants  Fifteen healthy volunteers aged 22 to 32 years.

Interventions  Forms of application included (1) nasal drops applied with a pipette, (2) nasal spray, and (3) a system producing squirts. Blue food dye was used to visualize the intranasal distribution of the liquid. The investigation was performed using nasal endoscopy.

Main Outcome Measure  Intranasal distribution of the dye was judged by 2 independent observers blinded to the applicator system used.

Results  The nasal drops predominantly reached the nasal floor. The nasal spray was widely distributed in the nasal mucosa; however, most of it was intercepted by the middle turbinate and did not reach the olfactory cleft effectively. Using the squirt system, the olfactory cleft was reached in most participants.

Conclusions  Previous failure of therapy with locally applied drugs in the case of sinonasal smell disorders may be partly due to the fact that the drugs did not reach the olfactory cleft when using traditional forms of application (ie, sprays). However, using an applicator producing squirts seems likely to present the drugs more effectively to the olfactory epithelium. Thus, it may be hypothesized that therapy could be more effective using a squirt system.

Design  Case-control study.

Setting  Ambulatory section of the Department of Otolaryngology, Hospital de Base de Brasília.

Patients  Thirty-seven individuals with tinnitus and 38 without tinnitus, with ages ranging from 20 to 45 years and pure-tone thresholds of 25 dB or better at frequencies between 500 and 8000 Hz.

Main Outcome Measures  We compared the latencies of waves I, III, and V; the interpeak intervals I-III, III-V, and I-V; the interaural latency difference (wave V); and the V/I amplitude ratio between the 2 groups.

Results  Among the 37 patients in the study group, abnormal results were found in 16 (43%) in at least 1 of the 8 parameters evaluated. When we analyzed the latencies, although the values were on average in the normal range used in the present study, the tinnitus group presented a significant prolongation of the latencies of waves I, III, and V when compared with the control group. Furthermore, we found the interpeak I-III, III-V, and I-V values to be within the normal limits, but the interpeak III-V value was significantly (P = .003) enlarged in the study group compared with the control group. The V/I amplitude ratio found in the tinnitus group was within normal limits; however, a significant (P = .004) difference was found when the 2 groups were compared. The averages of the interaural latency difference (wave V) did not show significant differences in relation to the control group.

Conclusions  We conclude that, although the averages obtained in several analyzed parameters were within normal limits, the ABR results from the patients with and without tinnitus and normal hearing are different, suggesting that ABR might contribute to the workup of these patients. Our data show that there are changes in the central pathways in the study group. The meaning of these changes must be further investigated.

Design  Retrospective case-series study.

Setting  Tertiary care university hospital.

Patients  Eighty-five patients (85 ears) with fresh extensive cholesteatomas who underwent canal wall down tympanoplasty with soft-wall reconstruction as first-stage surgery and a second operation after 1 year to confirm residual cholesteatomas and perform ossiculoplasty.

Main Outcome Measures  The incidence and localization of residual cholesteatomas in the middle ear were compared between surgery using the canal wall down and open tympanoplasty and canal wall up tympanoplasty. Possible technical causes of the residua were reviewed in a retrospective videotape analysis of the first-stage operations.

Results  Of the 85 ears operated on, 18 had residual cholesteatomas, for an overall incidence of 21%, with 1 residuum per ear. Six cholesteatomas were located in the epitympanum (33%), 3 in the sinus tympani (17%), 3 in the antrum (17%), 2 on the stapes (11%), 2 on the tympanic membrane (11%), 1 on the tympanic portion of the facial canal (6%), and 1 just under the skin of the external auditory canal (6%). The retrospective videotape analysis revealed that the main cause of residual cholesteatomas in the epitympanum and sinus tympani was incomplete removal of the matrix under an indirect surgical view because of insufficient drilling. Residual matrix in a bony defect in the middle cranial fossa or facial canal was the cause of residual cholesteatomas in the antrum or facial canal. Inappropriate keratinizing epithelium rolling during tympanic membrane or external auditory canal reconstruction was the cause of residual cholesteatomas in the tympanic membrane or external auditory canal.

Conclusions  The incidence of residual cholesteatomas in patients who underwent canal wall down tympanoplasty with soft-wall reconstruction was similar to that in patients who underwent surgery involving the canal wall down and open tympanoplasty or canal wall up tympanoplasty. In terms of localization, with canal wall down tympanoplasty with soft-wall reconstruction, there is the possibility of residua not only in the tympanic cavity but also in the antrum or mastoid cavity, as with the canal wall up method. Results of this study suggest that in patients with extensive cholesteatoma, canal wall down tympanoplasty with soft-wall reconstruction should be followed by a second procedure to detect any residual cholesteatomas in the tympanic cavity, antrum, or mastoid cavity.

Design  Histopathologic comparison of wild-type S pneumoniae and its mutants deficient in PspA, PsaA, and Ply.

Setting  Otopathology Laboratory, Department of Otolaryngology, University of Minnesota Medical School, Minneapolis.

Participants  Forty young chinchillas (weight, 250-350 g) with normal external auditory canals and tympanic membranes.

Intervention  Animals were divided into 3 groups and bullae inoculated with wild-type S pneumoniae serotype 2, strain D39, or its mutants deficient in PspA, PsaA, or Ply. Two days after inoculation, bullae were processed for light microscopy and transmission electron microscopy.

Main Outcome Measures  Comparison of inflammatory cell infiltration and penetration of bacteria into the round window membrane and adjacent scala tympani.

Results  Histopathologic findings using wild-type S pneumoniae and Ply^– mutant were similar and included otitis media and the presence of inflammatory cells and damage to and passage of bacteria through the RWM. Although otitis media was seen with the PspA^– and PsaA^– mutants, we observed no passage of bacteria through the RWM.

Conclusions  Both PspA and PsaA affect the ability of S pneumoniae to penetrate the RWM. Understanding the role of S pneumoniae virulence proteins in the pathogenesis of the middle ear, RWM, and inner ear will provide new strategies for the prevention and treatment of otitis media and its complications.

Design  Retrospective, uncontrolled, consecutive case series.

Setting  A tertiary care pediatric otolaryngologypractice.

Patients  Eighteen drooling and aspirating children.

Intervention  Transoral interruption of parotid and submandibular ducts using vascular clips.

Main Outcome Measures  Manifestations of poor saliva control (visible drooling, number of shirts and bibs used, choking episodes, embarrassment, and incidence of salivary aspiration), Glasgow Children's Benefit Inventory scores (possible score range, – 100 to + 100), and complications.

Results  Eighteen patients (10 boys and 8 girls) were treated in 14 months. Patient age ranged from 2 to 14 years. Follow-up ranged from 3 to 18 months. No complications occurred. Nine patients had no drooling at all after surgery. There was a significant reduction in the number of bibs and shirts used (P < .001). Regarding measures indicating circumoral skin problems, embarrassment, choking episodes, and aspiration pneumonia, all the patients had significant improvements after surgery. The mean Glasgow Children's Benefit Inventory score was 33.2.

Conclusions  Salivary duct clipping is an efficient and safe method of controlling saliva in neurologically challenged children. The operation positively affects the children's quality of life.

Design  An immunohistochemical study of recurrent tonsillitis with or without hypertrophy and adenoid tissue.

Setting  Academic medical center.

Patients  The study population comprised 15 patients with RTTH, 15 patients with recurrent tonsillitis (RT), 9 patients with adenoid vegetation, and 6 controls.

Main Outcome Measures  The following outcome measures were investigated: follicle number and follicular area and circumference; degree of papillary arrangement and keratin cyst in crypts; fibrosis; and density of S-100⁺ cells, CD20⁺ cells, CD45RO⁺ cells, lymphocytes and plasma cells, and cyclin D₁⁺ cells in surface epithelium, crypt epithelium, extrafollicular area, and follicles.

Results  In the RTTH group, follicle number and follicular area and circumference, S-100⁺ cell density in crypt and surface epithelium, and CD20⁺ cell density in crypt epithelium were higher than in the RT group. The other measures were lower in the RTTH group than in the RT group. In patients with RTTH, the increase in follicle number and S-100⁺ cell density in surface epithelium and decrease in cyclin D₁⁺ cell density in surface epithelium were significant. The number of CD45RO⁺ cells was unchanged, while S-100⁺ cell density increased in surface epithelium; however, in the RTTH group, CD20⁺ cell density, together with cyclin D₁⁺ cell density, decreased in surface epithelium when compared with the RT group. Also, there was a 50% decrease in cyclin D₁⁺ cell density in follicles, but CD20⁺ cell density decreased minimally in follicles. In the RTTH group, the increase or decrease in the number of cyclin D₁–expressing cells was parallel with the increase or decrease in the number of CD20⁺ cells in the areas without follicles.

Conclusions  Tonsil hypertrophy occurred with follicular hyperplasia and hypertrophy. There is a deficiency of proliferating active cells in response to mitogenic stimulation in RTTH. New follicles might have formed with B cells supplied from other sites because of the deficiency of proliferating active cells.

Design  Retrospective review.

Setting  Tertiary care academic center.

Patients  The study population comprised 35 patients who underwent rhinoplasty with TPCC between November 2003 and October 2004.

Interventions  The TPCCs were used for full-length dorsal grafts in all 35 patients, as well as for septal batten, spreader graft, septal extension, tip onlay, and shield grafts.

Main Outcome Measures  Surgical outcomes were evaluated in 35 patients who underwent rhinoplasty in which TPCC was used. Anthropometric measurements of the nose were made on lateral photographs and compared with preoperative measurements. Postoperative complications were also assessed.

Results  Anthropometric measurements, expressed as mean (SD), documented postoperative increases in tip projection (5% [9%]), nasal length (10% [10%]), nasolabial angle (1.5° [8.7°]), and nasofrontal angle (3.1° [8.7°]). The overall complication rate was 31% (11 of 35 patients). Complications included resorption (17%), warping (9%), visible graft contour (3%), and graft fracture (3%).

Conclusion  Although TPCC could serve as an alternative graft material for rhinoplasty, the high complication rates of this material may preclude its use for dorsal augmentation.

Design  Single-institution retrospective study.

Setting  A single tertiary care teaching hospital of Sungkyunkwan University School of Medicine.

Patients  Ninety-six patients with unilateral vocal fold motion impairment.

Interventions  Percutaneous Artecoll injection laryngoplasty under local anesthesia.

Main Outcome Measures  Acoustic, aerodynamic, and stroboscopic analyses were performed before injection and 1 week and 3, 6, and 12 months after injection. Two speech-language pathologists performed the perceptual assessment, and we used the subjective rating of hoarseness by the patients.

Results  The maximal phonation time, shimmer (amplitude variation), jitter (frequency variation), and ratio of noise to harmonic showed significant improvement 3 months after injection; these improvements were maintained 12 months after injection (P < .05). The GRBAS scale (overall grade of hoarseness, roughness, breathiness, asthenicity, and strain) grades and subjective patient-rated scores of hoarseness improved from 1 week after injection, and the improvements were maintained 12 months after injection (P < .05). We observed no significant early or delayed adverse events.

Conclusion  Injection laryngoplasty with Artecoll is a safe, useful, and durable treatment option for the management of glottal insufficiency secondary to unilateral vocal fold motion impairment.

Design  Retrospective review.

Setting  Tertiary care medical center.

Patients  We previously reported on the favorable clinical response to intralesional cidofovir therapy in 13 adult subjects. The subjects were enrolled in an open-trial prospective study (1997-2001) and completed the injection-only treatment protocol, and all subjects achieved a disease remission after a mean of 6 injections. In the present study, we review the clinical course of these subjects during an extended observational period (2001-2006).

Intervention  Patients with documented relapse of disease underwent additional intralesional cidofovir injections.

Main Outcome Measures  Additional interventions, disease severity, and adverse outcomes are reported.

Results  Following the original cidofovir protocol, 6 patients (46%) received no further interventions. The remaining 7 patients (54%) required further treatment for disease relapse, with a mean duration of remission before relapse of 1.05 years. Of the 7 patients who experienced disease relapse, 2 continued to have stable disease with regular injections, 2 were lost to follow-up during relapse treatment, and 3 achieved disease remission again. For this latter cohort, the mean number of injections per year necessary to achieve a second remission was 3.82. This compares with a mean of 1.77 injections per year that these patients received on an as-needed basis prior to the original study.

Conclusion  Intralesional cidofovir injections have been shown to be an effective therapy for adult laryngeal papilloma and should be considered in those patients who experience disease relapse.

Design  Retrospective study.

Setting  Ear, nose, and throat department, Tabriz University of Medical Sciences, Tabriz, Iran.

Patients  A total of 1121 patients with central tympanic membrane perforation were evaluated after tympanoplasty.

Interventions  Tympanoplasty was performed with the underlay technique using temporal facial graft.

Main Outcome Measure  The patients were followed up to assess the postoperative incidence of ITMC.

Results  During the follow-up period of 5 years, ITMC was observed in 9 patients (0.8%). Of these 9 patients, 8 were asymptomatic and had intact tympanic membranes. The asymptomatic cases were detected 1 to 2 years after surgery during routine follow-up examinations. Only 1 of 9 patients had otorrhea, which was due to a posterior perforation away from the location of the ITMC. The most common site of the ITMC was near the umbo.

Conclusions  Even after tympanoplasty with underlay technique, ITMC may develop between the layers of the tympanic membrane. The most common location of these cholesteatomas is near the umbo, which may be the result of insufficient removal of the residual squamous epithelium from the handle of the malleus. The cholesteatomas are usually asymptomatic and can be detected during routine follow-up examinations 1 to 2 years after surgery. Although ITMCs are usually noninvasive in nature, a review of the literature revealed that in rare cases they can also show a rapid and invasive growth pattern. Early detection and removal of these asymptomatic cholesteatomas during routine postoperative follow-up examinations can prevent their progression as well as consequent residual problems and complications.

Design  Randomized controlled trial.

Subjects  Ninety newly hatched Roman chickens.

Intervention  Chickens were injected with kanamycin monosulfate (200 mg/kg/d) for 10, 13, 17, 20, 25, or 30 days.

Results  Scanning electron microscopy revealed that hair cells in the proximal 40% of the basilar papilla degenerated and disappeared after 10 days of kanamycin treatment. Following this, hair cell regeneration and repair was apparent. Regeneration and maturation of hair cells within 20 days in chickens that received treatment for 20 days were similar to those in chickens that were treated for 10 days followed by 10 days of recovery. After 25 days of treatment, many regenerated hair cells of mature appearance were reinjured. Regenerated hair cells of immature appearance were not damaged. The auditory brainstem response assay showed that the loss and recovery thresholds in chickens treated with kanamycin for 20 days were similar to those in chickens treated for 10 days followed by 10 days of recovery. There was a loss of auditory brainstem response thresholds in chickens that were treated with kanamycin for more than 20 days.

Conclusion  The immature regenerated hair cells in the basilar papilla of chickens are resistant to kanamycin ototoxic effects; however, this resistance is not seen in mature hair cells following prolonged kanamycin exposure.

Design  Retrospective case series.

Setting  Academic, tertiary care medical center.

Patients  Fifteen consecutive patients with surgically confirmed meningoencephalocele of the mastoid and middle ear, without a history of trauma, tumor, cholesteatoma, or surgery of the mastoid or cranium, who were treated at our institution between January 1, 1999, and December 31, 2006.

Results  Ten of the 15 patients were women. Ages ranged from 31 to 77 years, with 12 patients 50 years or older. The most common presenting complaint was new-onset hearing loss in 14 patients, followed by aural fullness and headache. Cerebrospinal fluid formed an effusion in the middle ears of 13 patients and was most commonly identified when myringotomy resulted in continuous clear otorrhea. Four subjects had a history of adult-onset recurrent acute otitis media with intermittent otorrhea, which in 1 case was complicated by brain abscess. At least 1 full-thickness defect of the tegmen associated with cortical thinning of the middle fossa floor was identified in all cases on high-resolution computed tomography. At surgery, herniations of meningeal and cerebral tissue were seen through 1 (7 cases) or 2 (8 cases) defects in the middle fossa floor. Obstruction of antral aeration by the meningoencephalocele was present in all 4 cases associated with otitis media.

Conclusions  The onset of otitis media, including middle ear effusions at 40 years or older, warrants the consideration of a meningoencephalocele of the ear. The appearance of tegmental defects and cortical thinning of the middle fossa floor on computed tomography provides a strong indication of the diagnosis and of the need for surgical repair.

Design  The activity of mometasone (0.01%, 0.1%, and 0.5%) in buffer solution against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pyogenes, and Streptococcus milleri was tested by quantitative killing assays.

Setting  In vitro study.

Main Outcome Measure  Reduction of viable bacteria and fungi in quantitative killing assays.

Results  Mometasone (0.5%) reduced viable counts of S pyogenes and S milleri by 99.99% and 99.00%, respectively, after 24 hours of incubation, whereas colony-forming units (CFUs) of S aureus, P aeruginosa, and E coli were not affected by the corticoid. Mometasone (0.1%) caused a decrease in CFUs of S pyogenes of 99.90% to 99.99%, while it led to a 99.00% reduction in CFUs of S milleri, but only if low bacterial counts of 1 x 10⁴ CFUs/mL were incubated. By contrast, the use of mometasone at a low concentration (0.01%) demonstrated an increase in CFUs of S milleri if the baseline bacterial count was low (1 x 10⁴ CFUs/mL).

Conclusion  Mometasone demonstrates antimicrobial activity against streptococci.

Design  Eight primary cultures of NPFs were established from nasal polyps. Effects of EGCG on the production of hypoxia-inducible factor (HIF)–1 (the most potent VEGF stimulant) and VEGF by NPFs under hypoxic conditions were measured by Western blot analysis. Immunohistochemical staining was used to examine the in vivo expressions of HIF-1 and VEGF in 20 sections of nasal polyps.

Results  Western blot analysis showed that cobalt chloride induced HIF-1 and VEGF synthesis in NPFs in a time-dependent manner, reaching a plateau at 4 and 8 hours, respectively, following treatment. Epigallocatechin-3-gallate attenuated the level of HIF-1 induced by cobalt chloride and also reduced cobalt chloride–stimulated VEGF production by suppressing HIF-1 synthesis. Furthermore, oligomycin (a specific HIF-1 inhibitor) combined with EGCG resulted in a more profound inhibition of VEGF synthesis compared with oligomycin or EGCG treatment alone. Nevertheless, the synergistic effect seemed smaller than the sum of their individual actions. Immunohistochemical analysis revealed the presence of HIF-1 and VEGF in NPFs and mononuclear round cells. Intimate alignment of VEGF-positive fibroblasts and proliferating small capillaries was frequently found.

Conclusions  Nasal polyp fibroblasts contribute to the pathogenesis of nasal polyps by producing VEGF to promote angiogenesis under hypoxic conditions. Epigallocatechin-3-gallate substantially diminishes HIF-1 and VEGF synthesis in NPFs.

Design  Prospective, randomized, placebo-controlled trial.

Setting  Academic medical center.

Patients  Thirty-six subjects were randomized, and 23 completed the study.

Interventions  Subjects were randomized to receive 40 mg of citalopram hydrobromide or matching placebo (hereinafter, citalopram group and placebo group, respectively) for 12 weeks with a final visit at 16 weeks.

Main Outcome Measures  The Hamilton Depression Rating Scale, psychiatric interview, and the University of Washington Quality of Life (UW-QOL) and Clinician Global Impression–Severity (CGI-S) scales.

Results  The numbers of subjects who met predefined cutoff criteria for depression during the 12 weeks of active study were 5 of 10 (50%) taking placebo and 2 of 12 (17%) taking citalopram (Fisher exact test, P = .17). No patients in the citalopram group became suicidal, compared with 2 in the placebo group. Global mood state at the conclusion of the study as measured by the CGI-S scale was rated as at least mildly ill in 15% of those receiving citalopram compared with 60% in the placebo group (Fisher exact test, P = .04). Quality of life, measured by the UW-QOL, deteriorated in both groups from baseline but less so in the citalopram group.

Conclusions  This study reports data from the first depression prevention trial in HNC and suggests that prophylactic treatment may decrease the incidence of depression during HNC therapy. The clinical significance of the reduction in depression was best demonstrated by the CGI-S scale, which showed a notable difference in global psychiatric and physical well-being.

Participants  Committee for Neck Dissection Classification, American Head and Neck Society; representation from the Committee for Head and Neck Surgery and Oncology, American Academy of Otolaryngology–Head and Neck Surgery (T.A.D.).

Evidence  Review of current literature on neck dissection classification.

Consensus Process  Semiannual face-to-face meetings of the Committee for Neck Dissection Terminology and e-mail correspondence.

Conclusions  Standardization of terminology for neck dissection is important for communication among clinicians and researchers. New recommendations have been made regarding the following: boundaries between levels I and II and between levels III/IV and VI; terminology of the superior mediastinal nodes; and the method of submitting surgical specimens for pathologic analysis.

Design  Based on DNA microarray data from our laboratory and data reported in the literature, we identified 6 potential biomarkers of OSCC to investigate further. We used quantitative real-time polymerase chain reaction to examine expression changes of CDH11, MMP3, SPARC, POSTN, TNC, and TGM3 in OSCC and histologically normal control tissues. We further examined validated markers at the protein level by immunohistochemical analysis of OSCC tissue microarray sections.

Results  Quantitative real-time polymerase chain reaction analysis revealed upregulation of CDH11, SPARC, POSTN, and TNC gene expression and decreased TGM3 expression in OSCC tissue compared with control tissue; MMP3 was not found to be differentially expressed. In tissue microarray immunohistochemical analyses, SPARC (secreted protein, acidic, rich in cysteine), periostin, and tenascin C exhibited increased protein expression in tumor tissue compared with control tissue, and their expression was primarily localized within tumor-associated stroma rather than tumor epithelium. Conversely, transglutaminase 3 protein expression was found only within keratinocytes in control tissue and was significantly downregulated in cancer cells.

Conclusions  Of 6 potential gene markers of OSCC, initially identified by DNA microarray analyses, differential expression of CDH11, SPARC, POSTN, TNC, and TGM3 were validated by quantitative real-time polymerase chain reaction. Differential expression and localization of proteins encoded by SPARC, POSTN, TNC, and TGM3 were clearly shown by tissue microarray immunohistochemical analysis.

Design  A molecular biology study. The VEGF-C coding sequence was cloned into an expression vector and stably transfected into the SCCHN cell line SCC116 to create the SCC116-VEGFC line. RNA interference (RNAi) was used to block VEGF-C expression. An adenoviral system for expressing VEGF-C RNAi was developed and tested.

Setting  An academic hospital laboratory.

Main Outcome Measures  Relative VEGF-C RNA levels were determined by real-time quantitative reverse transcriptase–polymerase chain reaction, and protein expression was evaluated by Western blot. Cellular invasion was evaluated by 24-hour semipermeable membrane transit assay.

Results  SCC116-VEGFC cells had markedly increased expression of VEGF-C protein and RNA compared with normal SCC116 controls. SCC116-VEGFC cells produced marked increases in cellular invasion and motility compared with SCC116 cells. Blockade of VEGF-C expression by transfection of a VEGF-C RNAi expression plasmid into both SCC116 and SCC116-VEGFC cells induced a 38% decrease in SCCHN invasion and motility as tested by a semipermeable membrane invasion assay. We developed an adenoviral expression system for VEGF-C RNAi, which also induced a dose-dependent decrease in cellular invasion in the highly invasive DM12 cell line.

Conclusions  These studies demonstrate that intracellular VEGF-C levels modulate in vitro SCCHN motility and invasion. Further work is needed to clarify the specific receptors and signaling pathways that are involved in SCCHN motility. Molecular therapies that inhibit the VEGF-C pathway may have clinical potential in the treatment of lymphatic metastasis in SCCHN.

Design  Marker expression and clinical outcome.

Patients  Pretreatment tumor biopsy specimens were analyzed from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Study.

Main Outcome Measures  Expression of p53 (OMIM TP53) and Bcl-xL (OMIM 600039) in pretreatment biopsy specimens was assessed for correlation with chemotherapy response, laryngeal preservation, and survival.

Results  Higher rates of larynx preservation were observed in patients whose tumors expressed p53 vs those that did not (80% [36 of 45 patients] vs 59% [24 of 41 patients], P =.03). Higher rates of larynx preservation were also observed in patients whose tumors expressed low levels of Bcl-xL vs high levels of Bcl-xL (90% [18 of 20 patients] vs 60% [30 of 50 patients], P =.02). Patients were categorized into 3 risk groups (low, intermediate, and high) based on their tumor p53 and Bcl-xL expression status. Patients whose tumors had the high-risk biomarker profile (low p53 expression and high Bcl-xL expression) were less likely to preserve their larynx than patients whose tumors had the intermediate-risk biomarker profile (high p53 expression and low or high Bcl-xL expression) or the low-risk biomarker profile (low p53 expression and low Bcl-xL expression). The larynx preservation rates were 100% (10 of 10 patients), 77% (26 of 34 patients), and 54% (7 of 13 patients) for the low-risk, intermediate-risk, and high-risk groups, respectively (P =.04, Fisher exact test).

Conclusion  Tumor expression of p53 and Bcl-xL is a strong predictor of successful larynx preservation in patients treated with induction chemotherapy and followed by radiation therapy in responding tumors.

Design  Retrospective cohort analysis using the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. The Surveillance, Epidemiology, and End Results data were used to design 5 cohorts of patients with laryngeal cancer: 1977-1978, 1983-1984, 1989-1990, 1995-1996, and 2001-2002. Five-year survival rates were analyzed according to tumor site, stage, and grade; age at diagnosis;