Archives of Otolaryngology recent issues

Archives of Otolaryngology - Head & Neck Surgery provides timely information for physicians and scientists concerned with diseases of the head and neck. Published monthly, it includes peer-reviewed clinical and basic research from an array of disciplines. Archives is the official publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc., the American Head and Neck Society, and the American Society of Pediatric Otolaryngology.

White-tailed ptarmigan [About the Cover]

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About This Journal [About This Journal]

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Clinical Usefulness of Positron Emission Tomography-Computed Tomography in Recurrent Thyroid Carcinoma [Original Article]

Objectives  To determine the efficacy of combined positron emission tomography–computed tomography (PET-CT) in identifying recurrent thyroid cancer and to elucidate its role in the clinical management of thyroid carcinoma.

Design  Retrospective study.

Setting  Tertiary care referral academic center.

Patients  One hundred twenty-four patients with previously treated thyroid carcinoma who underwent PET-CT.

Main Outcome Measures  PET-CT images were correlated with clinicopathologic information. The influence of PET-CT findings on disease status determination and the treatment plan was evaluated.

Results  Among 121 patients undergoing iodine I 131 (¹³¹I) imaging (an ¹³¹I image was unavailable for 3 patients), 80.6% had negative findings on ¹³¹I imaging before undergoing PET-CT. Among 75 patients who had positive findings on PET-CT, 71 were true positive results. Among 49 patients who had negative findings on PET-CT, 32 were true negative results. Therefore, PET-CT demonstrated a sensitivity of 80.7%, specificity of 88.9%, positive predictive value of 94.7%, and negative predictive value of 65.3%. A significant difference was noted in the mean serum thyroglobulin levels between patients with positive vs negative PET-CT findings (192.1 vs 15.0 ng/mL, P = .01) (to convert thyroglobulin level to micrograms per liter, multiply by 1.0). Overall, distant metastases were detected in 20.2% of patients using PET-CT. There was an alteration of the treatment plan in 28.2% of patients as a result of added PET-CT information, and 21.0% of patients underwent additional surgery.

Conclusions  PET-CT is usually performed in patients with thyroid cancer having elevated thyroglobulin levels but non-¹³¹I–avid tumors and has high diagnostic accuracy for identifying local, regional, and distant metastases. Additional information from PET-CT in patients with ¹³¹I-negative and thyroglobulin-positive tumors frequently guides the clinical management of recurrent thyroid carcinoma.

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Time-Resolved Fluorescence Spectroscopy as a Diagnostic Technique of Oral Carcinoma: Validation in the Hamster Buccal Pouch Model [Original Article]

Objective  To investigate the benefit of using time-resolved, laser-induced fluorescence spectroscopy for diagnosing malignant and premalignant lesions of the oral cavity.

Design  The carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) was applied to 1 cheek pouch of 19 hamsters. The contralateral pouch and the cheek pouches of 3 hamsters without DMBA exposure served as controls.

Setting  University of California, Davis.

Participants  Twenty-two golden/Syrian hamsters.

Intervention  A nitrogen pulse laser was used to induce tissue autofluorescence between the wavelengths of 360 and 650 nm.

Main Outcome Measures  Spectral intensities and time-domain measurements were obtained and compared with the histopathologic findings at each corresponding site.

Results  Spectral intensities and lifetime values at 3 spectral bands (SBs; SB1 = 380 ± 10 nm; SB2 = 460 ± 10 nm, and SB3 = 635 ± 10 nm) allowed for discrimination among healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma. The lifetime values at SB2 were the most important when distinguishing the lesions using only time-resolved parameters. An algorithm combining spectral fluorescence parameters derived from both spectral and time-domain parameters (peak intensities, average fluorescence lifetimes, and the Laguerre coefficient [zero-order]) for healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma provided the best diagnostic discrimination, with 100%, 100%, 69.2%, and 76.5% sensitivity and 100%, 92.2%, 97.1%, and 96.2% specificity, respectively.

Conclusions  The addition of time-resolved fluorescence-derived parameters significantly improves the capability of fluorescence spectroscopy–based diagnostics in the hamster buccal pouch. This technique provides a potential noninvasive diagnostic instrument for head and neck cancer.

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Surgical Treatment of Buccofacial Region Vascular Anomalies Using an Intraoral Buccomucosal Flap Procedure [Original Article]

Objective  To report our experience in and our surgical technique of treating vascular anomalies of the buccofacial region using an intraoral buccomucosal flap approach.

Design  Retrospective medical record review and illustration of a specific surgical procedure.

Setting  Academic tertiary care center.

Patients  Thirty-two patients with vascular anomalies of the buccofacial region who have been treated using the intraoral buccomucosal flap approach.

Intervention  Surgical therapy using an intraoral buccomucosal flap approach.

Main Outcome Measures  Surgical outcomes and complications.

Results  Thirty-two patients were treated using the intraoral buccomucosal flap approach. The vascular anomalies treated at this site were venous malformations (17 [53.1%]), lymphatic malformations (13 [40.6%]), and hemangiomas (2 [6.3%]). Surgical removal was accomplished without occurrence of facial nerve dysfunction or other morbidity. The most frequent postoperative problem encountered was scarring with lymphatic malformation treatment.

Conclusion  The intraoral buccomucosal flap procedure is an effective surgical technique for treating vascular anomalies of the buccofacial region.

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Thyroid Cancer Outcomes in Filipino Patients [Original Article]

Objective  To compare the outcomes of patients having thyroid cancer among Filipinos vs non-Filipinos.

Design  Retrospective medical record review.

Setting  High-volume tertiary referral center in Toronto, Ontario, Canada.

Patients  A total of 499 patients with thyroid cancer (36 Filipino and 463 non-Filipino) treated at Mount Sinai Hospital from January 1, 1984, to August 31, 2003, with a minimum 5-year follow-up period and a minimum 1.0-cm tumor size. Patients were identified from a thyroid cancer database. Data on patient, tumor, and treatment factors were collected along with outcomes.

Main Outcome Measures  The presence of thyroid cancer recurrence, the rate of death from disease, and the time to recurrence.

Results  The 2 groups were similar for sex, age, history of head and neck radiation exposure, family history of thyroid cancer, follow-up time, tumor size, tumor pathologic findings, presence of tumor multifocality, stage of primary disease, type of thyroid surgery, use of postoperative radioactive iodine therapy, and use of external beam radiation therapy. Filipino patients experienced a thyroid cancer recurrence rate of 25% compared with 9.5% for non-Filipino patients (odds ratio, 3.20; 95% confidence interval, 1.23-7.49; P = .004). On multivariate analysis, the increased risk of thyroid cancer recurrence persisted for Filipino patients (odds ratio, 6.99; 95% confidence interval, 2.31-21.07; P < .001). No significant differences were noted between Filipino patients and non-Filipino patients regarding the rate of death from disease (5.6% vs 1.9%) and the time to recurrence (52.6 vs 53.1 months).

Conclusions  Filipino patients have a significantly higher risk of thyroid cancer recurrence compared with non-Filipino patients. However, no significant difference was noted in the time to recurrence or the rate of death from disease. These findings justify a more aggressive initial management and follow-up regimen for Filipino patients with thyroid cancer.

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Role of Radiotherapy in the Treatment of Nasoethmoidal Adenocarcinoma [Original Article]

Objective  To assess the efficacy of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

Design  Multicenter, retrospective study.

Setting  Eleven French hospitals.

Patients  The medical records of 418 patients who presented with nasoethmoidal adenocarcinoma from January 1, 1976, through December 31, 2001, were evaluated. A total of 324 patients were treated with a combination of surgery and radiotherapy, and 55 were treated with surgery only.

Main Outcome Measures  Survival rates, disease recurrence, and postoperative complications.

Results  The 5-year Kaplan-Meier survey revealed survival rates of 64.5% for the surgery-only group and 70.8% for the combined-treatment group. In the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2 regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31 patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant). Immediate postoperative complications in the combined-treatment group were hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1 patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and 5 died postoperatively.

Conclusion  The results of this retrospective study suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but its usefulness should be confirmed with further prospective studies.

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The Impact of Baseline Intact Parathyroid Hormone Levels on Severity of Primary Hyperparathyroidism and Outcomes in Patients Undergoing Surgery [Original Article]

Objective  To determine the impact of intact parathyroid hormone (iPTH) baseline levels on severity of primary hyperparathyroidism (PHPT) and outcomes following parathyroidectomy for PHPT.

Design  Single institution retrospective review.

Setting  Academic tertiary care center.

Patients  A total of 447 consecutive patients undergoing parathyroid surgery for PHPT.

Main Outcome Measures  Comparison of patients with high (≥150 pg/mL) and low (<150 pg/mL) baseline iPTH values; preoperative serum calcium, alkaline phosphatase, and 25-hydroxyvitamin D levels; and 6-month postoperative serum calcium and iPTH levels.

Results  A total of 304 patients had baseline iPTH values of at least 150 pg/mL (high baseline group), and 143 patients had baseline iPTH values lower than 150 pg/mL (low baseline group). Patients in the high baseline group had significantly higher levels of preoperative serum calcium, serum alkaline phosphatase, and adenoma weights (P < .001 for all comparisons). Serum 25-hydroxyvitamin D levels were significantly lower in patients in the high baseline group (P < .001). Sestamibi scans were more likely to localize an adenoma in the high baseline group (83.7%) than in the low baseline group (68.9%) (P < .01). There were no differences in the serum calcium and iPTH levels between the 2 groups 6 months after surgery.

Conclusions  Patients in the high baseline group undergoing surgery for PHPT had higher baseline levels of serum calcium, serum alkaline phosphatase, and parathyroid adenoma weights and lower serum 25-hydroxyvitamin D levels compared with the lower baseline group. Sestamibi scans were more likely to localize an adenoma in the high baseline group (83.7%) than in the low baseline group (68.9%) (P < .01). Despite an apparently lower rate of positive preoperative sestamibi scans for the low baseline group, patients were able to achieve a similar rate of disease cure as other patients with higher baseline iPTH levels. It seems that baseline iPTH level should not be used as a criterion to perform surgery or not perform surgery for patients with PHPT.

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Oncolysis Using Herpes Simplex Virus Type 1 Engineered to Express Cytosine Deaminase and a Fusogenic Glycoprotein for Head and Neck Squamous Cell Carcinoma [Original Article]

Objective  To determine if prodrug conversion of fluorocytosine to fluorouracil by an engineered herpes virus, OncoVEX^GALV/CD, enhances oncolytic therapy of head and neck squamous cell carcinoma.

Design  We assessed the ability of OncoVEX^GALV/CD and OncoVEX^GFP to infect, replicate within, and lyse 4 head and neck squamous cell carcinoma lines in vitro. The effects of adding fluorocytosine with OncoVEX^GALV/CD were evaluated.

Results  Head and neck squamous cell carcinoma was permissive to green fluorescent protein expression in100% of cells by OncoVEX^GFP at a multiplicity of infection of 1 after 48 hours and supported logarithmic viral replication. Virus caused more than 60% cell death 6 days after exposure to virus at a multiplicity of infection of 0.1 in 3 of the 4 cell lines. Fluorocytosine did not enhance cytotoxicity induced by OncoVEX^GALV/CD at a multiplicity of infection of 0.1. However, for the least-sensitive SCC25 cell line, virus at a multiplicity of infection of 0.01 was cytotoxic to only 4% of cells after 6 days but was cytotoxic to 35% of cells with fluorocytosine.

Conclusions  OncoVEX^GALV/CD efficiently infects, replicates within, and lyses head and neck squamous cell carcinoma at relatively low viral doses. Prodrug conversion by cytosine deaminase did not enhance therapy at viral doses that cause efficient cytotoxicity but may have beneficial effects in less-sensitive cell lines at low viral doses.

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Reproducibility of Clinical Grading of Tonsillar Size [Original Article]

Objective  To determine the reproducibility of the Brodsky grading scale and the modified 3-grade and 5-grade scales in reporting the size of the tonsils.

Design  Retrospective review of 60 video recordings of tonsil examination by 12 independent observers with different clinical backgrounds and various levels of training. The sizes of the tonsils were graded using different grading scales.

Setting  Tertiary care university hospital.

Participants  The video recordings were chosen from an ongoing epidemiologic study of sleep-related breathing disorder in children in Hong Kong.

Main Outcomes Measures  The intraobserver and interobserver reproducibility of each grading scale was determined using intraclass correlation. An intraclass correlation coefficient (ICC) exceeding 0.75 was set a priori to indicate an acceptable level of reliability.

Results  The mean intraobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5-grade scales were 0.858, 0.830, and 0.865, respectively. The mean interobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5-grade scales were 0.763, 0.739, and 0.783, respectively.

Conclusion  The Brodsky grading scale and the modified 5-grade scale achieved acceptable intraobserver and interobserver reproducibility.

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Subglottic Stenosis Examined as a Fibrotic Response to Airway Injury Characterized by Altered Mucosal Fibroblast Activity [Original Article]

Objective  To investigate the association between mucosal fibroblast activity and subglottic stenosis (SGS) development.

Design  Prospective study of an animal model of SGS.

Setting  Academic research laboratory.

Subjects  New Zealand white rabbits were assigned to either the cricothyroidotomy and carbon dioxide laser injury group or the cricothyroidotomy and silver nitrate injury group. Airways were excised for histologic analysis and the establishment of primary fibroblast cultures. Lesions from surgical excision of established SGS and subglottic tissue were used to analyze SGS recurrence.

Interventions  The subglottis was approached via cricothyroidotomy and was subjected to either carbon dioxide laser or silver nitrate injury before closure. The SGS lesions were excised at 8 to 10 weeks and were used to establish explants for fibroblast culture. The animals underwent recovery for an additional 14 days to follow recurrence of SGS. After 14 days, all the animals were killed humanely, and subglottic tissue was harvested for histologic evaluation. Rates of migration and contraction of SGS and normal airway fibroblasts were assayed using established in vitro methods under basal conditions and with prostaglandin E₂ treatment.

Main Outcome Measures  For in vivo studies, injury, healing, and scarring of the mucosa and cartilage were the primary measures. For cultured fibroblast experiments, cellular responses of fibroblasts from normal and stenosed mucosa were compared and contrasted.

Results  Mucosal injury resulted in acute fibroplasia and chronic SGS, surgical excision of mature SGS at 8 weeks resulted in rapid recurrence of stenosis, and SGS-derived fibroblasts were relatively refractory to the effects of prostaglandin E₂ on migration and contraction.

Conclusions  Subglottic stenosis represents a fibrotic airway repair process that involves fibroblasts that produce recurrent, excessive scar formation. We suggest that SGS development and recurrence may be partially dictated by altered fibroblast responsiveness to antifibroplastic signals during mucosal repair.

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Pediatric Primary Anterior Laryngotracheoplasty: Thyroid Ala vs Costal Cartilage Grafts [Original Article]

Objective  To compare outcomes with the use of thyroid ala cartilage (TAC) and costal cartilage (CC) grafts in pediatric primary anterior laryngotracheoplasty (LTP).

Design  Retrospective comparison study.

Setting  Tertiary, academic children's hospital.

Patients  Of 45 laryngotracheal operations performed between June 2001 and October 2008 for laryngotracheal stenosis, 29 were primary anterior LTPs. The procedures used either TAC (n = 24) or CC (n = 5) grafts and were planned as either single-stage (TAC group, 22 patients; CC group, 2 patients) or multistage (TAC group, 2 patients; CC group, 3 patients).

Main Outcome Measures  Operative time, length of intubation, graft-specific complications, need for additional airway procedures, and overall decannulation rate.

Results  The mean (SD) operative times were 222 (56) minutes for TAC grafts and 363 (59) minutes for CC grafts (P = .005). For single-stage LTPs that were decannulated, the mean (range) length of intubation was 3.3 (1-11) days for TAC grafts (n = 18) and 3 (1-5) days for CC grafts (n = 2) (P = .90). Graft-specific complications occurred in 17% of TAC grafts (n = 4) and 20% of CC grafts (n = 1) ( > 0.05). Symptomatic stenosis requiring additional surgical intervention occurred in 43% of TAC grafts (n = 10) and 60% of CC grafts (n = 3) ( > 0.05). Patients underwent decannulation in 83% of TAC grafts (n = 19) and 80% of CC grafts (n = 4) ( > 0.05).

Conclusions  In primary anterior LTPs, TAC grafts require significantly less operative time than CC grafts (P = .005). There were no statistically significant differences in length of intubation, frequency of graft-specific complications, or decannulation rates between TAC and CC grafts in primary anterior LTPs.

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Update on Bone-Anchored Hearing Aids in Pediatric Patients With Profound Unilateral Sensorineural Hearing Loss [Original Article]

Objective  To evaluate the use of bone-anchored hearing aids (Bahas) in children with single-sided deafness.

Design  Retrospective 3-year chart review.

Setting  Arkansas Children's Hospital, Little Rock, pediatric hospital serving children from birth to 21 years of age.

Patients  The study included 23 children (14 girls and 9 boys) with single-sided deafness (mean age, 12.6 years; age range, 6-19 years).

Interventions  Two-stage Baha surgery with 6-month osseointegration was performed on children 5 years and older at a single institution. The Baha processor was placed 2 weeks after the second-stage surgery.

Main Outcome Measures  Results of the Hearing in Noise Test (HINT) and the Children's Home Inventory for Listening Difficulties (CHILD) questionnaires were compared before and after Baha activation in children with profound unilateral sensorineural hearing loss.

Results  Preimplant mean HINT scores at speech-noise ratios of 0, +5, and +10 dB were 42%, 76%, and 95%, respectively. Postimplant mean HINT scores improved to mean speech-noise ratios of 82%, 97%, and 99% at 0, 5, and 10 dB, respectively. The CHILD scores also improved from mean preimplant ratings of 4.49 and 4.60 for patients and parents, respectively, to postimplant ratings of 6.90 and 7.10. Both teenagers (n = 15) and children younger than 13 years (n = 7) demonstrated improved HINT and CHILD scores. The complication rate was 17%.

Conclusion  Bone-anchored hearing aids are a durable treatment option that can achieve noticeable improvements in hearing in noise and in listening difficulties in children with profound unilateral sensorineural hearing loss.

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Low Heritability of Tinnitus: Results From the Second Nord-Trondelag Health Study [Original Article]

Objective  To estimate the heritability of tinnitus.

Design  Self-report questionnaire data collected from August 1, 1995, through June 30, 1997, from individuals in the Nord-Trøndelag Hearing Loss Study (an integrated part of the Nord-Trøndelag Health Study) were used. The study also included information on first-degree family relationships, and age-corrected polychoric correlations of relatives' tinnitus status were calculated. A structural equation model was fit to the data, and the relative contributions of genes and unique environmental effects were estimated. Models that included sex-specific effects were also tested.

Setting  Nord-Trøndelag County, Norway.

Patients  A population-based sample of 12 940 spouses, 27 607 parent-offspring, and 11 498 siblings was used. A total of 28 066 respondents were tested twice, yielding a test-retest correlation of 0.65 for the report of tinnitus.

Main Outcome Measure  Heritability of tinnitus.

Results  Correlations for parent-offspring ranged from 0.01 to 0.07 for the various sex combinations, sibling correlation ranged from 0.06 to 0.14, and the spouse correlation was 0.04. This family correlation pattern implies an upper limit for heritability of 0.11 with no sex differences in the heritability estimates.

Conclusions  This is the first large population-based family study, to our knowledge, to report on the heritability of tinnitus. In contrast to previous speculations in the literature, this low heritability indicates that additive genetic effects explain only a small proportion of the variance of tinnitus in the population.

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Delayed Epistaxis in External Dacryocystorhinostomy: Rate and Risk Factors [Original Article]

Objective  To report the incidence and risk factors associated with delayed epistaxis (2-8 days after the procedure) after external dacryocystorhinostomy (DCR).

Design  We identified and analyzed all cases of patients who underwent external DCR procedures at 2 institutions from January 1999 through December 2005. Cases of delayed epistaxis and their final surgical outcome were compared with those without it.

Setting  All patients who underwent surgery and were examined at 2 public hospitals in Melbourne, Australia.

Patients  A total of 374 patients who underwent 437 DCRs.

Interventions  Medical treatment, hospitalization, and endonasal examination with cautery.

Main Outcome Measures  Rate of delayed epistaxis and current and past use of antiplatelet medications.

Results  Of the 374 patients (mean [SD] age, 62 [18] years; 280 [75%] were women) who underwent 437 external DCRs, 15 (3.4%) had an episode of delayed epistaxis. They were generally older and more likely to have a history of active dacryocystitis compared with those who did not develop delayed epistaxis. Preoperative use of aspirin, nonsteroidal anti-inflammatory drugs, or warfarin sodium was not associated with delayed epistaxis or poorer surgical outcome if these anticoagulants were discontinued preoperatively as instructed. None of the 15 patients with delayed epistaxis had continued ingesting anticoagulants before undergoing DCR. Patients who developed epistaxis (80%) had a significantly lower rate of satisfactory surgical outcome than those who did not (90%) (P = .02).

Conclusion  The risk of delayed epistaxis should be similar for patients taking or not taking anticoagulant agents if their use is stopped within a defined period of time before DCR.

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Association of IL1A, IL1B, and TNF Gene Polymorphisms With Chronic Rhinosinusitis With and Without Nasal Polyposis: A Replication Study [Original Article]

Objective  To replicate and extend recent findings in a Turkish population of associations between chronic rhinosinusitis (CRS) with nasal polyposis and single-nucleotide polymorphisms (SNPs) in the IL1A (rs17561 and Ser114Ala), IL1B (rs16944), and TNF (rs361525 and rs1800629) genes.

Design  In a case-control replication study, DNA samples were obtained from 206 patients with severe CRS (cases) and from 196 postal code–matched controls. For IL1A and TNF, the 3 reported SNPs were complemented with tagging SNPs using an International HapMap genotyping data set to ensure complete genetic coverage. For IL1B, only the single reported SNP was assessed. A total of 24 SNPs (7 in IL1A, 1 in IL1B, and 16 in TNF) were individually genotyped. The PLINK software package was used to perform genetic association tests.

Setting  Academic research.

Patients  Canadian population of individuals with severe CRS.

Main Outcome Measures  Allelic differences between cases and controls.

Results  Significant allelic differences between cases and controls were obtained for IL1A rs17561 (odds ratio [OR], 1.48; P = .02). The following 3 additional SNPs in this gene were associated with CRS: rs2856838 (OR, 0.63; P = .003), rs2048874 (OR, 0.57; P = .01), and rs1800587 (OR, 1.49; P = .02). These 3 SNPs remained significant after correction for multiple testing. No association was found with IL1B or TNF.

Conclusions  We replicated the previously reported association between the IL1A polymorphism and severe CRS and identified 3 potential new associations in the same gene. This further supports the potential contribution of IL1A to the development of CRS. We were unable to replicate previous reports of associations with IL1B or TNF.

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A Case of Pyoderma Gangrenosum on the Nasal Dorsum [Clinical Note]

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Carotid Artery Spasm Secondary to Acute Isolated Sphenoid Sinusitis: Implications on Workup and Treatment [Clinical Note]

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Radiology Quiz Case 1 [Clinical Problem Solving: Radiology]

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Radiology Quiz Case 2 [Clinical Problem Solving: Radiology]

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Radiology Quiz Case 1: Diagnosis [Clinical Problem Solving: Radiology]

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Radiology Quiz Case 2: Diagnosis [Clinical Problem Solving: Radiology]

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Pathology Quiz Case 1 [Clinical Problem Solving: Pathology]

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Pathology Case Quiz 2 [Clinical Problem Solving: Pathology]

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Pathology Quiz Case 1: Diagnosis [Clinical Problem Solving: Pathology]

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Pathology Quiz Case 2: Diagnosis [Clinical Problem Solving: Pathology]

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Impact of Margin Status on Laser Surgery for Early Glottic Cancer [Letters to the Editor]

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Impact of Margin Status on Laser Surgery for Early Glottic Cancer--Reply [Letters to the Editor]

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Merced River, Yosemite National Park [About the Cover]

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About This Journal [About This Journal]

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Prevalence of Dysplasia in Juvenile-Onset Recurrent Respiratory Papillomatosis [Original Article]

Objectives  To quantify the prevalence of dysplasia and to evaluate the impact of use of cidofovir in recurrent respiratory papilloma biopsy specimens obtained from a pediatric population.

Design  Retrospective review of patient medical records and histopathologic test results from January 1, 1998, through December 31, 2008.

Setting  Children's Hospital of Wisconsin.

Patients  Patients with a history of operation treated for recurrent respiratory papillomatosis.

Main Outcome Measures  The presence or absence of dysplasia identified in a papilloma specimen and patient characteristics, such as age of initial presentation, number of operations, tobacco exposure, treatment for reflux, and use of cidofovir, were quantified.

Results  Treatment for recurrent respiratory papillomatosis was identified in 21 patients. Age at initial diagnosis ranged from 8 months to 14 years. A total of 123 recurrent respiratory papillomatosis specimens in 20 patients were identified. Dysplasia was seen in less than 1% of samples (1/123), which represents 5% of total patients. Seven patients (35%) received cidofovir treatment and none of them developed dysplasia. These data demonstrate a lack of correlation between cidofovir treatment and dysplasia, with the P value being nonsignificant (Fisher exact test, P=.4).

Conclusion  Dysplasia is a rare event in pediatric recurrent respiratory papillomatosis, and there does not appear to be an association between the use of cidofovir and dysplastic changes.

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Medical and Surgical Complications in Pediatric Cochlear Implantation [Original Article]

Objectives  To report complications of cochlear implantation (CI) in children and to analyze risk factors.

Design  Retrospective study from January 1, 1990, through April 30, 2008, with a mean follow-up of 5.5 years (range, 1 month to 17 years).

Setting  Tertiary academic center.

Patients  Four hundred thirty-four patients younger than 16 years. Mean age at CI was 4.7 (range, 0.6-16.0) years. Forty-one children (9.4%) underwent CI when younger than 24 months. Forty-three (9.9%) had inner ear malformations.

Main Outcome Measures  Complications after CI, classified into early (0-8 days) or delayed (>8 days) and major or minor. Spontaneous failures of internal devices were excluded. Correlation to age at CI, local trauma, and inner ear malformations were analyzed using the ² test.

Results  Forty-three patients (9.9%) experienced complications. Delayed complications occurred in 28 patients (65.1%), with a mean delay of 2.2 (range, 0.1-8.4) years. Twenty-four patients (5.5%) had major complications, consisting of severe cutaneous infections (15 patients), magnet displacement (3), meningitis (2), cholesteatoma (2), cerebrospinal fluid leak (1), and electrode misplacement (1). Nineteen (4.4%) had minor complications, consisting of vertigo (9 patients), soft-tissue infection (5), persistent otitis media (4), and facial palsy (1). Complications led to reimplantation in 13 of the 43 patients (30.2%). Trauma to the mastoid area (14 patients) and inner ear malformations (51) were highly correlated with major delayed complications (P < .001) and early minor complications (P < .001), respectively. Young age at CI was not correlated with any type of complication.

Conclusions  Complications of CI in children are common, with trauma as a major factor. Inner ear malformations should prompt specific preventive management. Cochlear implantation in young children did not appear to be a risk factor in this study.

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Abnormal Voicing in Children Using Cochlear Implants [Original Article]

Objectives  To measure acoustic voice outcomes in children with bilateral cochlear implants and to compare these with established norms, as well as to determine whether these acoustic measures were influenced by duration of cochlear implant use, age at implantation, and overall "time in sound."

Design  Cross-sectional study.

Setting  Pediatric tertiary care cochlear implant center.

Patients  All children using bilateral cochlear implants who were followed up during a 4-month period at our implant center were invited to participate. Twenty-seven children (17 males and 10 females) aged 3 to 15 years were enrolled. Causes of deafness included congenital (n = 8), genetic (n = 8), meningitis (n = 3), cytomegalovirus (n = 2), and unknown (n = 6). The interval between first and second implantations ranged from simultaneous to 7.8 years (mean, 4.2 years).

Main Outcome Measures  Children completed acoustic voice testing using a Computerized Speech Lab and a Multi-Dimensional Voice Program. Acoustic results were compared with those of children receiving unilateral implants and with normative data.

Results  Compared with established pediatric normative data, children with bilateral implants demonstrated poor control of long-term frequency perturbation and long-term amplitude perturbation when vocalizing sustained phonations (P < .001 for both). This finding was consistent with data previously reported in children using unilateral cochlear implants. Long-term control of frequency perturbation improved as children used their bilateral cochlear implants over time and was significantly influenced by overall time in sound (P = .02).

Conclusions  Similar to unilateral cochlear implant users, children using bilateral implants have difficulty controlling long-term frequency perturbation and long-term amplitude perturbation during sustained phonations. These measures improved as the duration of usable hearing increases.

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Neuroanatomic Differences in Children With Unilateral Sensorineural Hearing Loss Detected Using Functional Magnetic Resonance Imaging [Original Article]

Objective  Functional magnetic resonance imaging (fMRI) provides information about neuronal excitation by measuring changes in cerebral hemodynamics. This study used fMRI to compare neuroanatomic activation patterns in children with unilateral sensorineural hearing loss (USNHL) with the neuroanatomic activation patterns in normally hearing individuals.

Design  Patients were presented with narrowband noise and speech-in-noise tasks while undergoing fMRI of the brain. In the narrowband noise task, 5 chirps at center frequencies of 250 Hz, 500 Hz, 1 kHz, 2 kHz, and 4 kHz were presented monaurally for 1 second in a randomized order to children in both groups. In the speech-in-noise task, Bamford-Kowal-Bench (BKB) sentences were presented over 4-talker babble to both ears, and scans were acquired after each stimulus. We compared fMRI data across groups using independent component analysis and Bayesian (hierarchical) linear models.

Setting  Tertiary referral center.

Patients  Twelve children with USNHL and 23 normally hearing controls.

Interventions  Perform fMRI while subject listens to narrowband and speech-in-noise tasks.

Main Outcome Measures  Neuroanatomic differences in fMRI.

Results  In the narrowband noise task, children with USNHL had less activation of auditory areas and failed to activate auditory association areas and attention networks compared with normally hearing controls. In the speech-in-noise task, children with USNHL activated only secondary auditory processing areas in the left hemisphere, while controls activated these areas bilaterally. Children with right-sided USNHL failed to activate attention areas that were activated in controls and in children with left-sided USNHL. Only children with left-sided USNHL activated bilateral visual association areas.

Conclusions  Results show significant differences in the cortical processing of sound between children with severe to profound USNHL and normally hearing children. These differences may account for the functional auditory problems that children with USNHL experience.

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Assessment of Constipation in Children With Tracheostomy [Original Article]

Objective  To determine the prevalence of constipation among children with tracheostomy tubes compared with children without tracheostomy tubes. We theorize that patients with tracheostomy may be unable to achieve adequate subglottic pressure for the Valsalva maneuver, which may contribute to constipation.

Design  Prospective cohort study.

Setting  Tertiary care children's hospital.

Patients  Consecutive series of 36 children with tracheostomy and 72 general pediatric otolaryngology patients without tracheostomy.

Interventions  A pediatric constipation questionnaire (from previously published references) was given to parents of the study participants. Data were collected regarding patient medications, neurological status, and use of positive pressure airway assistance, speaking valves, and feeding tubes. Data were evaluated using ² and t tests. Logistic regression analysis was used to search for independent variables impacting presence of constipation.

Results  The mean ages for the tracheostomy and control groups were 6.8 and 4.7 years, respectively (P = .07). A history of constipation was elicited in 60% of children with tracheostomy compared with only 16.7% of controls (P < .001). More patients with tracheostomy tubes (80.0%) than controls (20.8%) were taking medication to treat constipation (P < .001). Constipation was also significantly associated with older age (P = .02), use of medications with constipation as a known adverse effect (P = .02), and the presence of neurodevelopmental impairment (P < .001). Constipation was still independently associated with the presence of a tracheostomy tube when correcting for age and the use of constipation-causing medications. When controlling for neurodevelopmental impairment, the presence of a tracheostomy tube was not proven to be an independent predictor of constipation.

Conclusion  Children with tracheostomy tubes are more likely to have a history of constipation, although a causal relationship between tracheostomy and constipation could not be determined due to the potentially confounding variable of neurodevelopmental delay.

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Pediatric Sialendoscopy: A 5-Year Experience at a Single Institution [Original Article]

Objectives  To evaluate the outcome of our experience in the treatment of salivary gland disorders in children undergoing sialendoscopy and to assess the evolution of the technique.

Design  Retrospective medical record review.

Setting  Tertiary care university hospital.

Patients  Thirty-eight children with salivary gland disorders undergoing diagnostic and interventional sialendoscopy between January 1, 2003, and November 30, 2008.

Intervention  Diagnostic and interventional sialendoscopy using general anesthesia.

Main Outcome Measures  Demographic, clinical, and surgical variables, including age, sex, date of first symptoms, parotid or submandibular location of disease, preoperative ultrasonographic results, sialendoscopy technique, sialendoscopy observations, and complications.

Results  Pediatric sialendoscopy was performed on the parotid gland in 23 patients (61%) and on the submandibular gland in 15 patients (39%). The most frequent indication for sialendoscopy was recurrent salivary gland swelling. Thirty-two of 38 procedures (84%) were performed endoscopically, whereas a combined intervention was necessary for 3 patients and a submandibular gland excision for another 3 patients. Sialendoscopy allowed the diagnosis of 12 patients with salivary duct lithiasis, 21 with salivary duct stenosis, and 2 with both submandibular lithiasis and stenosis, and findings from 3 sialendoscopies were normal. Preoperative ultrasonographic results were confirmed by sialendoscopy in only 7 patients. Of the 10 patients with lithiasis found using sialendoscopy, only 4 had been detected using preoperative ultrasonography.

Conclusions  Sialendoscopy is a pertinent technique for the diagnosis and treatment of salivary gland disorders in children. It also allows the most conservative treatment of sialolithiasis and juvenile recurrent parotitis.

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In Vitro Effects of Acid and Pepsin on Mouse Middle Ear Epithelial Cell Viability and MUC5B Gene Expression [Original Article]

Objective  To examine whether in vitro exposure of mouse middle ear epithelial cells (mMEECs) to conditions that mimic physiologic reflux upregulates Muc5b gene expression and alters cell viability.

Design  In vitro mMEEC model.

Setting  Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.

Participants  Cells from the immortalized mMEEC line.

Main Outcome Measures  Cell viability, the quantity of Muc5b messenger RNA abundance, and Muc5b promoter activity.

Results  The 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assays demonstrated an acidic dose-dependent decrease in cell survival, with pH less than 4 significantly decreasing viability at 1 hour. Pepsin had a mild protective effect up to 8 hours, with greater cell viability, in the pH range of 5.0 to 7.6. Reverse-transcriptase polymerase chain reaction demonstrated induction of Muc5b messenger RNA levels over controls after exposure to acidic pH levels of 5.7, and 4 with and without pepsin. Similarly, a pH of 4.0 significantly increased Muc5b promoter activation 5.4-fold. Pepsin at neutral or acidic pH values did not significantly alter Muc5b expression or promoter activity.

Conclusions  Despite decreasing cell viability, acidic pH drives middle ear epithelial Muc5b gene expression in vitro, which perhaps explains how laryngopharyngeal reflux can contribute to otitis media. Pepsin at neutral or acidic pH levels had minimal effects on Muc5b gene expression; thus, although pepsin may be a useful marker for detecting the presence of reflux, our results suggest that acid itself is a more likely pathologic component of gastric juice in the middle ear.

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Correspondence Between Subjective and Linear Measurements of the Palatal Airway on Lateral Cephalometric Radiographs [Original Article]

Objective  To evaluate the correlation between and significance of 2 methods of palatal airway assessment on lateral cephalographs.

Design  Diagnostic lateral cephalometric imaging study that took place from January 1, 2006, to December 31, 2007.

Setting  American University of Beirut Medical Center.

Patients  Children with chronic mouth breathing referred by a pediatric otolaryngologist for cephalometric evaluation by participating orthodontists.

Main Outcome Measures  Two distances were measured on the digitized lateral cephalographs between the adenoid and soft palate: the shortest adenoid distance (SAD) and the most convex adenoid distance (CAD). The palatal airway was assessed on a grade-1 to grade-3 scale independently by the referring otolaryngologist and an orthodontist.

Results  A total of 200 children were included in the study (127 boys and 73 girls; mean age, 6 years; age range, 1.71-12.62 years). High correlations were observed between the airway ratings gathered by both examiners (r = 0.96) and between SAD and CAD (r = 0.92). Significant correlations were noted between the palatal airway grade and the SAD and CAD measurements (r = –0.73 and r = –0.79, respectively). Shortest adenoid distance measures of 2 mm or less corresponded mostly to grade 3 obstruction and were more prevalent in patients younger than 6 years. Age was inversely proportional to both the grade and SAD (P < .001).

Conclusions  Both methods are reliable for assessment of airway obstruction by the adenoid. Because SAD and CAD are highly correlated, we recommend the use of SAD as a more readily identifiable distance on cephalometric radiographs. Removal of adenoids when SAD is less than 2 mm may be indicated because this condition reflects a severe airway obstruction associated with potential changes in dentofacial structure.

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Development of Cytomegalovirus-Mediated Sensorineural Hearing Loss in a Guinea Pig Model [Original Article]

Objective  To develop an animal model for cytomegalovirus (CMV)–induced sensorineural hearing loss.

Design  Guinea pig model.

Setting  University of Utah otolaryngology research labs.

Participants  Thirty-one Hartley guinea pig pups were divided into 4 groups. Group 1 pups were delivered from pregnant dams inoculated with 1 x 10⁵ plaque-forming units (PFU) of guinea pig CMV (gpCMV). Group 2 and group 3 pups were delivered from pregnant dams inoculated with higher doses of 2 and 4 x 10⁵ PFU of gpCMV, respectively. Group 4 pups, the control group, were delivered from uninoculated dams.

Main Outcome Measures  All groups underwent weekly auditory brainstem response studies. Six weeks after delivery, the brain, cochlea, salivary glands, lungs, liver, and kidneys were harvested. All tissue except the cochlea was analyzed for histologic evidence of the virus. All tissue underwent polymerase chain reaction (PCR) to detect gpCMV.

Results  Seven of the 19 (37%) inoculated pups developed a 30-dB hearing loss; none of the animals in the control group had a worse click threshold than 20 dB. Group 1 pups demonstrated statistically significant asymmetric hearing loss. All 3 inoculated groups showed evidence of progressive hearing loss over time. The control group did not demonstrate evidence of progressive threshold worsening. The PCR testing detected gpCMV in the cochleas of group 2 and group 3 animals.

Conclusions  We have successfully demonstrated elevated auditory brainstem response click thresholds with characteristics of progressive and asymmetric loss that have been reported in clinical reports of congenital CMV infection. We also detected gpCMV via PCR testing in the cochleas of inoculated pups.

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Effect of a Novel Anatomically Shaped Endotracheal Tube on Intubation-Related Injury [Original Article]

Objectives  To develop an anatomically shaped endotracheal tube (ETT) and to compare the degree of induced laryngeal injury of this ETT with that of a standard ETT using an animal model.

Design  Randomized controlled animal study.

Subjects  Eight Sus scrofa piglets (15-20 kg) randomly intubated with either a standard or a modified uncuffed ETT.

Interventions  The modified ETT was handcrafted by gluing and then trimming dry polyvinyl acetate foam circumferentially to the distal end of a standard uncuffed ETT. After intubation, the foam quickly self-expanded as it absorbed the secretions of the laryngopharynx and adopted the shape of the intraluminal airway. This conforming shape also sealed the larynx to allow for positive pressure ventilation. Both groups were intubated for 4 hours under constant hypoxic conditions (mean oxygen saturation <70%) to enhance and accelerate intubation damage. They were then humanely killed, and the larynx and trachea were harvested for histologic examination.

Main Outcome Measures  The severity of laryngeal injury graded on a scale from 0 to 4 (0 indicates normal; 1, epithelial compression; 2, epithelial loss; 3, subepithelial and glandular necrosis; and 4, perichondrium involvement).

Results  All of the specimens histologically demonstrated areas of inflammation and epithelial loss. The standard ETT caused substantial deep damage, with a mean (SD) severity score of 2.79 (0.74). The modified ETT caused mainly superficial damage, with a mean (SD) severity score of 1.65 (0.56) (P < .001).

Conclusion  The modified ETT objectively caused less laryngotracheal damage compared with the standard ETT and may be of potential clinical benefit.

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Single- vs Double-Stage Laryngotracheal Reconstruction [Original Article]

Objective  To compare single-stage laryngotracheal reconstruction (ssLTR) and double-stage LTR (dsLTR).

Design  Retrospective medical record review.

Setting  Tertiary care children's hospital.

Patients  Seventy-one patients underwent 84 procedures (22 ssLTRs and 62 dsLTRs).

Intervention  Review of preoperative disease severity and surgical outcomes for patients who underwent ssLTR vs dsLTR.

Main Outcome Measure  Operation-specific and overall decannulation rates.

Results  Regarding ssLTRs, the mean grade of subglottic stenosis was 2.1 and the overall and operation-specific decannulation rates were 100% and 91%, respectively. The mean grade of subglottic stenosis for double-stage procedures was 2.9, and the overall and operation-specific decannulation rates were 93% and 68%, respectively. Patients who underwent ssLTR and dsLTR were further divided into early and late groups based on whether the posterior graft was sutured in place (early) or not (late). Overall and operation-specific decannulation rates were 100% and 89%, respectively, for the early single-stage group and 100% and 92% for the late group. Regarding the dsLTR group, overall and operation-specific decannulation rates were 88% and 42%, respectively, for the early group and 95% and 79% for the late group. Among all groups, there was no significant difference in overall decannulation rates (P > .05). Single-stage LTR offered an increased rate of operation-specific decannulation over dsLTR (P < .05). However, that difference was not significant between the late ssLTR and the late dsLTR groups (P > .05).

Conclusion  Careful assessment of preoperative disease severity and overall medical status will help surgeons choose between ssLTR and dsLTR, maximizing patient outcomes for both modalities.

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Accuracy and Safety of Tracheoscopy for Infants in a Tertiary Care Clinic [Original Article]

Objective  To assess the diagnostic accuracy and safety of office-based tracheoscopy when combined with flexible fiberoptic laryngoscopy (FFLT). Flexible laryngoscopy on infants is routinely performed by otolaryngologists in the clinic. The addition of tracheoscopy may improve overall airway assessment but is rarely performed due to the suspected risk of airway compromise.

Design  A 6-year retrospective medical record review.

Setting  Tertiary care hospital.

Patients  Thirty-one infants younger than 1 year with complete data from preoperative FFLT and microlaryngoscopy and bronchoscopy (MLB) were examined.

Main Outcome Measures  Results from 241 MLB procedures were reviewed.

Results  Laryngomalacia (LM) and tracheomalacia (TM) were identified more often by FFLT than by MLB. In particular, the detection rate for LM and TM by MLB, as seen preoperatively by FFLT, was 79% and 61%, respectively. Compared with FFLT, MLB accurately diagnosed the severity of LM and TM only 55% and 65%, respectively, of the time. Fiberoptic laryngoscopy revealed synchronous airway lesions in 62% of infants with LM, while MLB discovered synchronous airway lesions in 54%. Static airway lesions were more frequently diagnosed with MLB. No respiratory events occurred during FFLT.

Conclusions  In an appropriate patient, FFLT is a safe and effective diagnostic tool for common infant tracheal and laryngeal abnormalities. Detection and characterization of dynamic airway lesions is better achieved by FFLT than by MLB.

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Endoscopic Surgical Treatment of Laryngotracheal Clefts: Indications and Limitations [Original Article]

Objective  To present the indications, techniques, results, and limitations of endoscopic surgical treatment of laryngotracheal cleft.

Design  Retrospective case note study (2005-2009).

Setting  Department of Otolaryngology–Head and Neck Surgery, Armand Trousseau Children's Hospital, Paris, France.

Patients  Eleven patients who underwent endoscopic cleft closure as a primary (n = 8) or secondary (n = 3) procedure among 22 patients treated for laryngotracheal clefts. We report patients' demographics, symptoms leading to the diagnosis, endoscopic evaluation method, medical examination results, and surgical techniques.

Intervention  Endoscopic closure of the cleft under spontaneous ventilation via 2-layer interrupted sutures after excision of the mucosal edge using a carbon dioxide laser in 10 patients and a thulium laser in 1.

Main Outcome Measures  Analysis of postoperative complications, revision surgery, need for intensive care unit admission, closure of the cleft, and long-term symptom results.

Results  Successful closure of the 11 clefts (with revision surgery in 3 patients) without the need for intubation or intensive care unit admission enabled the elimination of aspiration in 10 patients and significant improvement in 1 patient with bilateral vocal cord paralysis. There were no significant postoperative complications.

Conclusions  Endoscopic closure of laryngotracheal clefts is a reliable technique that significantly reduces perioperative and postoperative morbidity. The results of this technique are entirely satisfactory, and we suggest that it is suitable as a primary procedure for the treatment of type I, II, and III clefts extending to the cervical trachea, including in neonates.

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Diagnostic Contributions of Videolaryngostroboscopy in the Pediatric Population [Original Article]

Objective  Videolaryngostroboscopy (VLS) is a standard technique used for evaluating adult patients with dysphonia. However, while pediatric dysphonia affects 5% of children, children with dysphonia are traditionally examined with a flexible nasal endoscope. The purpose of this study was to determine whether VLS provides additional diagnostic yield in children.

Design  A retrospective medical chart review was conducted from 2001 to 2006.

Setting  Tertiary care center.

Patients  Pediatric patients aged 3 to 17 years (mean age, 11 years) who presented with prolonged dysphonia. All patients were previously examined by flexible laryngoscopy and treated with speech therapy for a presumed diagnosis of vocal cord nodules.

Interventions  Flexible or rigid VLS was performed.

Main Outcome Measure  The diagnosis per patient established after VLS.

Results  Eighty patients were included in the study: 50 underwent rigid VLS; 28 underwent flexible VLS; and 2 did not tolerate either procedure. A total of 132 diagnoses were made, including 68 benign mucosal diseases (41 nodules, 15 polyps, 8 cysts, and 4 sulci), 41 inflammatory disorders, 11 functional disorders, 6 congenital disorders, 4 traumatic injuries, and 2 neurologic disorders. Many patients received more than 1 intervention for their dysphonia, including antireflux medication and speech therapy, but 16 patients also underwent phonomicrosurgery.

Conclusions  Patients with a history of prolonged dysphonia for whom treatment has failed should be referred for evaluation by VLS. Videolaryngostroboscopy elucidates subtle features of different disease processes; clarifies the differences between benign mucosal disorders that might require surgical intervention; and helps identify inflammatory processes that contribute to dysphonia. To our knowledge, these findings have not previously been reported in the pediatric population. Although most pediatric dysphonia can be attributed to benign nodules, our results show that inflammatory conditions and benign lesions other than nodules contribute to dysphonia and are often overlooked and undertreated.

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Audiologic Phenotype and Progression in GJB2 (Connexin 26) Hearing Loss [Original Article]

Objectives  To document the audiologic phenotype of children with biallelic GJB2 (connexin 26) mutations, and to correlate it with the genotype.

Design  Prospective, observational study.

Setting  Tertiary care children's hospital.

Patients  Infants and children with sensorineural hearing loss (SNHL).

Intervention  Sequencing of the GJB2 (connexin 26) gene.

Main Outcome Measures  Degree and progression of SNHL.

Results  From December 1, 1998, through November 30, 2006, 126 children with biallelic GJB2 mutations were identified. Of the 30 different mutations identified, 13 (43%) were truncating and 17 (57%) were nontruncating; 62 patients had 2 truncating, 30 had 1 truncating and 1 nontruncating, and 17 had 2 nontruncating mutations. Eighty-four patients (67%) initially had measurable hearing in the mild to severe range in at least 1 of 4 frequencies (500, 1000, 2000, or 4000 Hz). Of these 84 patients with residual hearing, 47 (56%) had some degree of progressive hearing loss. Patients with 2 truncating mutations had significantly worse hearing compared with all other groups. Patients who had 1 or 2 copies of either an M34T or a V37I allele had the mildest hearing loss.

Conclusions  Hearing loss owing to GJB2 mutations ranges from mild to profound and is usually congenital. More than 50% of patients will experience some hearing loss progression, generally gradually but occasionally precipitously. Hearing loss severity may be influenced by genetic factors, such as the degree of preserved protein function in nontruncating mutations, whereas hearing loss progression may be dependent on factors other than the connexin 26 protein. Genetic counseling for patients with GJB2 mutations should include the variable audiologic phenotype and the possibility of progression.

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Boundary Issues: A Case of Nontraumatic Bilateral Dehiscence of the Lamina Papyracea [Clinical Note]

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Skull Base Paraganglioma and Intracranial Hypertension [Clinical Note]

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Radiology Quiz Case 1 [Clinical Problem Solving: Radiology]

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Radiology Quiz Case 2 [Clinical Problem Solving: Radiology]

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Radiology Quiz Case 1: Diagnosis [Clinical Problem Solving: Radiology]

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Radiology Quiz Case 2: Diagnosis [Clinical Problem Solving: Radiology]

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Pathology Quiz Case 1 [Clinical Problem Solving: Pathology]

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Pathology Quiz Case 2 [Clinical Problem Solving: Pathology]

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Pathology Quiz Case 1: Diagnosis [Clinical Problem Solving: Pathology]

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Pathology Quiz Case 2: Diagnosis [Clinical Problem Solving: Pathology]

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Gentoo penguins in Antarctica [About the Cover]

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About This Journal [About This Journal]

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Reviewers Who Completed a Review During 2009 [Annual Reviewers List]

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Secondary Tracheoesophageal Puncture With In-Office Transnasal Esophagoscopy [Original Article]

Objective  To evaluate the outcomes of voice restoration using office-based transnasal esophagoscopy (TNE) to guide placement of the secondary tracheoesophageal puncture (TEP).

Design  Retrospective chart review.

Setting  Two tertiary care medical centers.

Patients  The study included 39 patients who underwent the TNE-TEP procedure from January 2004 to December 2008.

Main Outcome Measures  Clinical, demographic, and TE speech–related data were recorded to examine the ease, efficiency, complications, and speech-related outcomes.

Results  Among 39 patients identified, the average age was 65 years (age range, 47-83 years), with 32 male (82%) and 7 female (16%) patients. Twenty-five patients (64%) underwent total laryngectomy; 8 (21%) underwent total laryngectomy with partial pharyngectomy; and 14 (36%) underwent microvascular flap reconstruction. The overall success rate of secondary TNE-assisted TEP placement was 97% (n = 38), with 1 unsuccessful attempt. There was no statistically significant correlation found between patients having undergone radiation therapy (either before or after oncologic resection) or a cricopharyngeal myotomy and successful TEP placement, type of reconstruction used to close the pharyngeal defect when compared with the difficulty in the placement of the TEP, development of complications associated with TEP placement, use of the TEP prosthesis, or speech intelligibility at the last follow-up visit. Thirty-one patients (79%) were still using their TEP prosthesis for speech at the last follow-up visit. Of the patients reviewed, 28 (72%) had understandable TE speech.

Conclusions  In-office TNE-assisted TEP placement can safely be performed, with excellent speech outcomes. Reconstruction with musculocutaneous or microvascular free-tissue transfer did not limit our ability to place secondary TEPs with TNE.

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Intraoperative Laryngeal Nerve Monitoring During Thyroidectomy [Original Article]

Objective  To determine whether nerve integrity monitor testing during thyroidectomy predicts recurrent larygeal nerve (RLN) function after surgery.

Design  Prospective cohort outcomes study

Patients  The study included 210 consecutive patients with thyroid abnormalities who underwent thyroidectomy.

Methods  All patients were intraoperatively monitored with a nerve integrity monitoring system (Xomed NIM II; Medtronic Inc, Fridley, Minnesota), and their vocal cord function was assessed with fiberoptic laryngoscopy before and after surgery. Normal and impaired vocal cord function were compared using an independent t test with respect to postoperative vocal cord mobility, length of the RLN dissection, and the minimum stimulus needed to generate a response at the completion of surgery.

Results  There was a statistically significant difference between the stimulus in milliamperes required to stimulate normal vs abnormal functioning nerves at the completion of the procedure at the cricoarytenoid joint (P = .02) and at the distal end of the RLN dissection (P < .01). A greater length of dissected nerve was associated with normal vocal cord function; however, it was not statistically significant (P = .07).

Conclusion  These data suggest that an RLN that responds at lower-intensity stimulation (≤0.5 mA) at the end of thyroid surgery is associated with normal vocal cord mobility.

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The Role of Sentinel Lymph Node Biopsy in Differentiated Thyroid Carcinoma [Original Article]

Objective  To determine whether sentinel lymph node (SLN) biopsy can accurately predict central compartment metastasis in patients with differentiated thyroid carcinoma.

Design  Prospective clinical study.

Setting  Academic tertiary care center.

Patients  Ninety-eight patients (82 women and 16 men; mean age, 48.3 years) underwent a total thyroidectomy and central compartment dissection.

Intervention  Peritumoral injection of methylene blue dye, 1%, followed by SLN biopsy.

Main Outcome Measures  The final pathology report established the presence of metastasis among SLNs and lymph nodes that did not stain blue (non-SLNs [NSLNs]).

Results  Differentiated thyroid carcinoma was found in 75 of 98 patients (77%). Seventy of 75 patients with differentiated thyroid carcinoma presented with SLNs and/or NSLNs within the central compartment. Fifteen of 70 patients had metastasis-positive SLNs, while 55 had metastasis-negative SLNs. Six of 15 patients with positive SLNs also had positive NSLNs. No patients with negative SLNs were found to have positive NSLNs. Sentinal lymph node status was a highly significant predictor of NSLN result (Fisher exact test, P < .001). The accuracy, sensitivity, specificity, and positive and negative predictive values of SLN biopsy were 87%, 100%, 86%, 40%, and 100%, respectively.

Conclusions  To our knowledge, this is the largest series of SLN biopsy in patients with differentiated thyroid carcinoma. Our experience suggests that this is an accurate and noninvasive means to identify subclinical lymph node metastasis. Because negative SLNs correlate strongly with a negative central compartment (100% in this study, P < .001), this technique can be used as an intraoperative guide when determining the extent of surgery necessary in cervical level VI.

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Intraoperative Parathyroid Hormone Assay in Patients With Primary Hyperparathyroidism and Double Adenoma [Original Article]

Objective  To determine the utility of parathyroid hormone (PTH) monitoring for double adenomas (DAs).

Design  Retrospective chart review.

Setting  Tertiary referral center.

Patients  The study included 47 patients with primary hyperparathyroidism who had DAs identified during first-time parathyroid exploration.

Main Outcome Measures  Intraoperative PTH levels were measured in every case, and the intraoperative PTH assay and its influence on surgical outcome were examined.

Results  A total of 47 of 552 consecutive patients (8.5%) with primary hyperparathyroidism were found to have DAs; 457 patients (82.7%) had single adenomas; and 48 patients (8.6%) had disease in more than 2 glands. The mean (SD) age of the patients with DAs was 58 (14) years, and 26 patients (55%) were female. The mean (SD) preoperative intact PTH level was 129 (57) pg/mL (to convert to nanograms per liter, multiply by 1), and the preoperative serum calcium level was 11.0 (0.6) mg/dL (to convert to millimoles per liter, multiply by 0.25). In all patients, the intraoperative PTH levels decreased by 79.7% (11.4%) from baseline after removal of both abnormal parathyroid glands. When the location could be confirmed, the second adenoma was ipsilateral in 17 patients (36%) and contralateral in 27 patients (64%). The mean (SD) postoperative intact PTH level was 46 (26) pg/mL at 6 months, and the cure rate was 98%.

Conclusions  Intraoperative PTH monitoring and maintenance of normocalcemia after surgery confirm previous reports that DAs do exist and are not simply missed cases of 4-gland hyperplasia. Intraoperative PTH monitoring accurately predicted the success of parathyroidectomy in 98% of patients with DAs.

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Adverse Events Associated With Concurrent Chemoradiation Therapy in Patients With Head and Neck Cancer [Original Article]

Objective  To assess toxicities, functional outcomes, and health-related quality of life associated with concurrent chemoradiation therapy (CRT) in patients with head and neck cancer.

Design  Prospective and retrospective outcomes study.

Setting  Tertiary care institution.

Patients  Participants in the longitudinal Outcomes Assessment Project whose head and neck cancer was treated with CRT between February 1, 2000, and March 1, 2007 (n = 104).

Interventions  Patients prospectively provided functional and health-related quality of life information, including data from the 1-year and most current follow-up visits. Medical records were reviewed to determine toxicity and survival rates.

Main Outcome Measures  Well-defined acute and late toxicities; functional outcomes (diet, dentition, tracheostomies); head and neck cancer–specific, general health, and depression outcomes; and survival rates.

Results  Most patients had oropharyngeal or laryngeal tumors (87.5%) and advanced-stage disease (75.0%). Approximately one-half had hematologic toxicities and toxicity-related treatment delays. Approximately one-quarter had neurotoxicities and/or ototoxicites, moist desquamation, pneumonia, nausea and vomiting requiring hospitalization or intravenous fluids, dehydration or malnutrition requiring hospitalization, and mild or moderate fever. Although patients receiving the current intensity-modulated radiation therapy (IMRT) protocol using the Pinnacle³ planning system had more toxicity-related treatment delays, they had fewer toxicities and better functional and health-related quality of life outcomes compared with those receiving conventional lateral opposing-field radiation or the initial IMRT protocol using the Best nomos PEACOCK planning system.

Conclusions  Patients receiving CRT experience a substantial number of treatment-related adverse events, primarily affecting oropharyngeal and laryngeal function, with improvement noted for the current IMRT protocol. Improving dental prosthetic rehabilitation and including evaluations with speech and swallowing pathologists before and during treatment may enhance patient outcomes.

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Endoscopic Resection of Sinonasal Cancers With and Without Craniotomy: Oncologic Results [Original Article]

Objective  To evaluate the oncologic outcomes of patients with sinonasal cancer treated with endoscopic resection.

Design  Retrospective review.

Setting  Tertiary care academic cancer center.

Patients  All patients with biopsy-proved malignant neoplasm of the sinonasal region who were treated with endoscopic resection between 1992 and 2007 were included in the study, and their charts were reviewed for demographics, histopathologic findings, treatment details, and outcome.

Main Outcome Measures  Oncologic outcomes, including disease recurrence and survival.

Results  Of a total of 120 patients, 93 (77.5%) underwent an exclusively endoscopic approach (EEA) and 27 (22.5%) underwent a cranioendoscopic approach (CEA) in which the surgical resection involved the addition of a frontal or subfrontal craniotomy to the transnasal endoscopic approach. Of the 120 patients, 41% presented with previously untreated disease, 46% presented with persistent disease that had been partially resected, and 13% presented with recurrent disease after prior treatment. The most common site of tumor origin was the nasal cavity (52%), followed by the ethmoid sinuses (28%). Approximately 10% of the tumors had an intracranial epicenter, most commonly around the olfactory groove. Tumors extended to or invaded the skull base in 20% and 11% of the patients, respectively. An intracranial epicenter (P < .001) and extension to (P = .001) or invasion of (P < .001) the skull base were significantly more common in patients treated with CEA than in those treated with EEA. The primary T stage was evenly distributed across all patients as follows: T1, 25%; T2, 25%; T3, 22%; and T4, 28%. However, the T-stage distribution was significantly different between the EEA group and the CEA group. Approximately two-thirds (63%) of the patients treated with EEA had a lower (T1-2) disease stage, while 95% of patients treated with CEA had a higher (T3-4) disease stage (P < .001). The most common tumor types were esthesioneuroblastoma (17%), sarcoma (15%), adenocarcinoma (14%), melanoma (14%), and squamous cell carcinoma (13%). Other, less common tumors included adenoid cystic carcinoma (7%), neuroendocrine carcinoma (4%), and sinonasal undifferentiated carcinoma (2%). Microscopically positive margins were reported in 15% of patients. Of the 120 patients, 50% were treated with surgery alone, 37% received postoperative radiation therapy, and 13% were treated with surgery, radiation therapy, and chemotherapy. The overall surgical complication rate was 11% for the whole group. Postoperative cerebrospinal fluid leakage occurred in 4 of 120 patients (3%) and was not significantly different between the CEA group (1 of 27 patients) and the EEA group (3 of 93 patients) (P > .99). The cerebrospinal fluid leak resolved spontaneously in 3 patients, and the fourth patient underwent successful endoscopic repair. With a mean follow-up of 37 months, 18 patients (15%) experienced local recurrence, with a local disease control of 85%. Regional and distant failure occurred as the first sign of disease recurrence in 6% and 5% of patients, respectively. The 5- and 10-year disease-specific survival rates were 87% and 80%, respectively. Disease recurrence and survival did not differ significantly between the EEA group and the CEA group.

Conclusions  To the best of our knowledge, this is the largest US series to date of patients with malignant tumors of the sinonasal tract treated with endoscopic resection. Our results suggest that, in well-selected patients and with appropriate use of adjuvant therapy, endoscopic resection of sinonasal cancer results in acceptable oncologic outcomes.

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Oropharyngeal Cancer: A Case for Single Modality Treatment With Transoral Laser Microsurgery [Original Article]

Objective  To demonstrate the role of transoral laser microsurgery (TLM) in the treatment of oropharyngeal cancer.

Design  A 2-center retrospective case series analysis.

Setting  Two tertiary care medical centers.

Patients  The study population comprised 69 patients with previously untreated select T1 to T3, N0 to N2 squamous cell carcinoma of the oropharynx, of whom 44 (74%) had no indication for adjuvant RT and 25 (36%) had an indication for adjuvant RT to the neck alone but declined radiotherapy. The primary tumor sites were the tonsil (n = 28 [41%]), tongue base (n = 28 [41%]), pharyngeal wall (n = 8 [12%]), soft palate (n = 4 [6%]), and vallecula (n = 1 [1%]).

Interventions  Transoral laser microsurgery in 69 patients, with neck dissection in 59 patients (83%).

Main Outcome Measures  Complications, local and regional control, overall and disease-specific survival, swallow function, and feeding tube dependence.

Results  Over the mean follow-up period of 44 months, 66 of 69 patients had no disease recurrence at the primary site. The 5-year local control estimate was 94%. The mean duration of hospitalization was 3 days. There were no major complications relating to TLM. No patient required a permanent feeding or tracheostomy tube. For stage I, II, and III disease, the 5-year Kaplan-Meier estimates of locoregional control were 90%, 73%, and 70%, respectively. The 5-year overall survival estimate was 86%.

Conclusions  Transoral laser microsurgery alone with or without neck dissection is an effective approach for select T1 to T3, N0, or N1 oropharyngeal cancer. Low levels of morbidity, short treatment duration, and excellent disease control make it an attractive therapeutic strategy. The treatment option of endoscopic-assisted laser microsurgery should be discussed by the multidisciplinary team for patients presenting with tumors suitable for this approach.

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Transoral Resection for Squamous Cell Carcinoma of the Base of the Tongue [Original Article]

Objective  To review the oncologic and functional outcomes of patients with squamous cell carcinoma of the base of the tongue who underwent transoral tumor resection and neck dissection with or without postoperative adjuvant therapy.

Design  Retrospective medical record review.

Setting  Tertiary referral center.

Patients  All patients undergoing transoral resection of squamous cell carcinoma on the base of the tongue as part of their primary treatment from January 1, 1996, through January 31, 2005.

Main Outcome Measures  We analyzed overall survival, disease-specific survival, local control, and locoregional control rates using the Kaplan-Meier method. Speech and swallowing function and treatment-related morbidity were also analyzed.

Results  A total of 20 patients underwent transoral resection. Four patients had surgery only, 12 had surgery and radiotherapy, and 4 had surgery and chemoradiotherapy. One patient had stage II disease, 3 had stage III disease, and 16 had stage IVA disease. The Kaplan-Meier overall survival rate was 90.0%, and the disease-specific survival rate was 94.7% at 2 years, with a mean follow-up of 3.7 years. Median hospital stay was 4.7 days. Patients who received a tracheostomy underwent decannulation with a median tracheostomy time of 5.5 days. Seven of 9 patients who received a percutaneous endoscopic gastrostomy tube had it removed. Three patients developed local recurrence, there were no regional recurrences, and 2 patients developed distant metastasis.

Conclusions  Transoral resection of squamous cell carcinoma of the base of the tongue with postoperative adjuvant therapy provided excellent local and regional control and minimized morbidity. Transoral resection is a reasonable treatment option for patients with oropharyngeal squamous cell carcinoma, resulting in very low overall loss of organ function in properly selected patients.

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Location of Bacterial Biofilm in the Mucus Overlying the Adenoid by Light Microscopy [Original Article]

Objective  To determine the location of bacteria and biofilm in adenoid tissue and in mucus overlying the adenoid.

Design  Adenoids removed in 1 piece were oriented to the cephalic and caudal ends. Mucus was fixed by the gradual addition of Carnoy fluid. Consecutive histologic sections were stained with periodic acid–Schiff for visualization of the exopolysaccharide matrix, Giemsa for visualization of bacteria and cells, and fluorescent in situ hybridization with a universal probe for visualization of bacteria.

Setting  Department of Otolaryngology–Head and Neck Surgery, University of Virginia.

Participants  We obtained adenoids from children 10 years or younger who had chronic adenotonsillitis or obstructive sleep apnea. Twenty-seven adenoids were used to develop the fixation method. We examined histologic sections from 9 of 10 adenoids fixed using the final fixation protocol. One adenoid that was missing the surface epithelium was excluded from further evaluation.

Main Outcome Measure  Identification of bacteria by light microscopy.

Results  Bacteria in large numbers were present in the mucus overlying the surface of all 9 adenoids; bacteria were not found in the parenchyma of the adenoids below the epithelial surface. Bacterial biofilms were present on 8 of the 9 adenoids. Sessile (attached) biofilm was present on the caudal end of only 1 adenoid. Multiple planktonic (unattached) biofilms were present on 7 adenoids, always in areas not subject to mucus flow. Biofilms were most common on the caudal portions of adenoids.

Conclusions  Bacteria of the adenoid reside in secretions on the surface and in crypts. Biofilms, predominantly planktonic, were present on 8 of 9 adenoids excised because of hypertrophy. Whether biofilms have a role in the causation of adenoid hypertrophy is not known.

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Diagnostic Value of Nasal Allergen Challenge Combined With Radiography and Ultrasonography in Chronic Maxillary Sinus Disease [Original Article]

Objective  To investigate the possible role of nasal allergy in chronic disease of the maxillary sinuses (CDMS) by means of nasal provocation test (NPT) with allergen combined with radiography and ultrasonography.

Design  Prospective clinical controlled study.

Setting  Academic referral center.

Patients  Seventy-one patients with CDMS and 16 control subjects with allergic rhinitis but no history of sinus disease.

Interventions  In the 71 patients, a total of 135 NPTs and 71 control challenges with phosphate-buffered saline were performed by rhinomanometry combined with radiography and ultrasonography. In the control patients, 16 positive NPTs were repeated and combined with radiography and ultrasonography.

Main Outcome Measures  Number, type, and timing of nasal responses with accompanying changes on radiographs and ultrasonograms.

Results  Of the 71 patients, 67 developed 104 positive nasal responses of various types (P < .001), 89 of which were accompanied by significant changes on radiographs (P = .008), whereas 83 were also associated with significant changes on ultrasonograms (P = .007). No significant changes on the radiographs or the ultrasonograms were recorded during the 71 phosphate-buffered saline control tests in the patients with CDMS (P = .14 and .06, respectively) or during the 16 NPTs in control subjects (P = .15 and .12, respectively). The radiographic and ultrasonographic findings were significantly correlated (r = 0.81; P < .01).

Conclusions  Nasal allergy may be involved in some patients with CDMS, resulting in appearance of a maxillary sinus response. Monitoring this response by means of serial ultrasonography and, if necessary, also by conventional radiography or computed tomography simultaneously with the nasal challenge with allergen seems to be a very useful diagnostic supplement allowing additional therapeutic measures focused on the nasal allergy.

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Cutting and Suture Technique of the Caudal Septal Cartilage for the Management of Caudal Septal Deviation [Original Article]

Objectives  To introduce the cutting and suture technique of the caudal L-strut for the management of caudal septal deviation and to evaluate its efficacy and surgical outcomes.

Design  Retrospective study.

Setting  Tertiary care rhinology clinic.

Patients  Forty-five patients who underwent endonasal septoplasty using the cutting and suture technique of the caudal L-strut.

Interventions  After elevation of the mucoperichondrial flap, deviated portions of cartilage and bone were excised, leaving at least a 1.5-cm strip of L-strut. If caudal septal deviation persisted, the caudal strut was cut at the convex-most part, and the cut ends were slightly overlapped and sutured together.

Main Outcome Measures  Improvement in the treatment of nasal obstruction using a visual analog scale and a questionnaire for subjective satisfaction were evaluated 2 to 6 months after septoplasty. To evaluate outcomes objectively, endoscopic photographs of the nasal cavity before and after surgery were evaluated by 2 independent surgeons.

Results  Significant improvement in the treatment of nasal obstruction was achieved, with mean visual analog scale scores of 7.93 preoperatively and 3.63 postoperatively (P < .001). Subjective satisfaction was rated as much improved in 68% of patients, improved in 15%, and no change in 17%. Endoscopic examinations showed that 51% of patients had near-complete correction of the septum and that 47% had improved but a little persisting caudal deviation. One patient had no change in caudal septal deviation on endoscopic examination.

Conclusion  The cutting and suture technique of the caudal L-strut seems to be a useful technique that can be performed with relative ease and simplicity.

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The Histologic Relationship of Preauricular Sinuses to Auricular Cartilage [Original Article]

Objective  To determine the histologic relationship and distance between excised preauricular epithelial sinus tract and the adjacent auricular cartilage (sinocartilaginous distance) in a series of patients. The excision of preauricular sinuses is a common surgical procedure. Recurrences are frequent and can be technically challenging. While advocated by several authors, the surgical removal of adjacent auricular cartilage is not universally performed.

Design  Retrospective case series.

Setting  Children's Hospital of Philadelphia.

Patients  Fifty-two pediatric patients who underwent surgical excision of preauricular sinus tracts and adjacent auricular cartilage.

Interventions  Between September 1, 2005, and July 31, 2007, the preauricular sinus tracts and adjacent auricular cartilage were excised from 52 pediatric patients. A pathologist reviewed a total of 58 specimens to determine the relationship between epithelial tract and cartilage.

Main Outcome Measure  The sinocartilaginous distance in microns.

Results  Patient ages ranged from 8 months to 17 years (mean age, 4 years). In all but 1 case, the tracts were in close proximity to the cartilage. The average sinocartilaginous distance was 472 µm (median distance, 400 µm); the 25th percentile was 250 µm. In over 50% of the specimens, the sinocartilaginous distance was less than 0.5 mm, and in nearly all of the these, the epithelial tract was in continuity with stromal tissue histologically indistinguishable from perichondrium.

Conclusions  The observed sinocartilaginous distances suggest that it may be difficult to dissect most sinus tracts from the cartilage. The routine removal of a small portion of auricular cartilage along with the sinus tract may yield a more thorough excision and help to prevent recurrence.

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Fall foliage [About the Cover]

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About This Journal [About This Journal]

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2009 American Head and Neck Society Presidential Address: Going Global, Reaching Out [Presidential Address]

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The Legacy and Obligations of the Head and Neck Surgeon: The 2009 Hayes Martin Lecture [Original Article]

I am delighted and extraordinarily honored to be asked to give the Hayes Martin Lecture to what is now the American Head and Neck Society. This lecture represents the crown jewel of the Society of Head and Neck Surgeons, a society that was composed primarily of general and plastic surgeons who focused on head and neck trauma and malignancies. The list of past Hayes Martin lecturers represents the greats of this specialty—names that for me had extraordinary impact and yet to those generationally behind me are, in all likelihood, unfamiliar: Oliver Bears, Charles Harrold, Harvey Baker, Richard Jesse, Milton Edgerton. Each led their society with a strong hand and attempted to keep the American Society for Head and Neck Surgery (composed predominantly of head and neck–focused otolaryngologists) at bay. A generation of conflict and contempt gradually seeped away to measured regard from both societies eventuating in a fraternal consolidation of the 2 into what is now the American Head and Neck Society. On May 13, 1998, the American Head and Neck Society evolved from a merger of the American Society for Head and Neck Surgery and the Society of Head and Neck Surgeons. The discipline has benefited measurably.

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Better Than Buffett?: A Report on the Success of the American Head and Neck Society Research Grant Program [Original Article]

It has been well established that a crisis exists in the biomedical research enterprise of clinical surgery departments: the extinction of the surgeon-scientist. A number of factors, including dwindling research funding, decreasing reimbursement from insurance providers, shrinking salaries for researchers, waning interest in academia among graduating residents, and financial pressures on departments for greater clinical productivity, have contributed to this phenomenon in recent years.¹ More importantly, the growing number of basic scientists who are competing with clinicians for investigator-initiated funding from the National Institutes of Health (NIH), along with the competitive advantage of clinicians from internal medicine specialties for these funds, has led to fewer awards to surgeons for research funds.² The downturn in the United States economy in 2008 has made these issues more pronounced, threatening the viability of many academic medical centers and the research enterprise in many surgical departments.

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Prophylactic Central Neck Dissection in Stage N0 Papillary Thyroid Carcinoma [Original Article]

Objective  To assess the disease-free survival results of prophylactic central neck dissection for papillary thyroid carcinoma preoperatively staged as N0.

Design  Inception cohort.

Setting  Head and neck surgery unit at a national oncologic center.

Patients  Patients with a histologically confirmed diagnosis of stage N0 papillary thyroid cancer but no previous oncologic treatment, no recurrent tumor, and no distant metastasis.

Intervention  Central neck dissection intended as curative treatment.

Main Outcome Measure  Disease-free survival. Demographic, clinical, therapeutic, pathologic, and neck recurrence information was also collected.

Results  A total of 266 patients were included. Mean (SD) follow-up time was 6.9 (4.3) years. Ninety percent of patients had a follow-up longer than 2 years. Prophylactic central neck dissection was performed in 136 patients (51.3%). Of those patients who underwent central neck dissection, 112 had metastatic lymph nodes (82.3%). Neck recurrence occurred in 45 patients (16.9%). Overall, 5-year neck disease–free survival was 86.8%; it was 88.2% in the central neck dissection group vs 85.6% in the group that did not undergo central neck dissection (P = .72). In the multivariate analysis, factors related to central neck dissection were macroscopic extrathyroidal extension (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.19-3.79) and multifocality (OR, 3.96; 95% CI, 2.08-7.53). In Cox multivariate analysis for disease-free survival, central neck dissection did not show any significant effect.

Conclusion  Prophylactic central neck dissection did not show any advantage in the rate of neck recurrence in patients with N0 clinical stage disease.

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Central Neck Dissection for Papillary Thyroid Cancer [Original Article]

Objective  To examine the role of central neck dissection (CND) in patients with papillary thyroid cancer (PTC).

Design  Retrospective analysis of patients treated for PTC between 1993 and 2008.

Setting  Academic institution.

Patients  All patients diagnosed with PTC who underwent surgical therapy at our institution.

Main Outcome Measures  Recurrence, hypocalcemia, hypoparathyroidism, and recurrent laryngeal nerve (RLN) injury.

Results  A total of 136 patients were treated for PTC, 26 of whom were excluded because their initial resection was performed at another institution. Of the 110 patients who underwent initial surgical therapy, CND was performed in 22 patients (20%), 18 with and 4 without enlarged nodes at the time of surgery. A mean (SD) of 11 (4) lymph nodes were removed, and lymph node metastases were identified in 17 patients (77%). One patient developed a recurrence in the lateral neck at 15 months' follow-up. Eighty-eight patients had no abnormal lymph nodes and did not undergo CND, 2 of whom developed a recurrence (2%) (P = .49) in the central neck at 14 months' and 11 years' follow-up. Permanent RLN injury occurred in no patient who underwent CND and in 1 patient without a CND (1%). Transient hypocalcemia occurred in 19 patients who underwent CND (86%) compared with 54 patients without a CND (61%) (P = .01). Permanent hypoparathyroidism occurred in 1 patient who underwent a CND (5%).

Conclusion  After total thyroidectomy and CND, recurrence in the central neck is uncommon, but hypocalcemia is more common, raising questions about the use of routine CND in patients with PTC.

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Recurrent Laryngeal Nerve: A Plexus Rather Than a Nerve? [Original Article]

Objectives  To analyze the frequency of extralaryngeal branching (ELB) of the recurrent laryngeal nerve (RLN) in a consecutive series of patients undergoing thyroidectomy by the same group of surgeons during an extended period and to compare our findings with the data available in the literature.

Design  Retrospective medical record study.

Setting  Academic research.

Patients  From March 1, 1983, to September 30, 2008, 2677 patients underwent thyroidectomy. Of these, 1638 patients had surgical information about at least 1 RLN. A total of 1081 patients underwent bilateral operations. During the last 5 years of the study, intraoperative laryngeal nerve monitoring was performed in selected patients using a commercially available system.

Main Outcome Measures  Information was obtained regarding 2154 RLNs.

Results  A total of 1390 RLNs (64.53%) had ELB. Among 447 patients in whom intraoperative laryngeal nerve monitoring was used, the anterior branches usually exhibited more electrophysiologic activity.

Conclusions  Extralaryngeal branching was found in 64.53% of RLNs in this case series. In recent patients with intraoperative laryngeal nerve monitoring, electrophysiologic activity was observed in the branches, particularly the anteriorly situated ones. Recognition of this frequent anatomical configuration and meticulous preservation of all branches are of paramount importance to decrease postoperative morbidity associated with thyroidectomy.

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Relation of Final Intraoperative Parathyroid Hormone Level and Outcome Following Parathyroidectomy [Original Article]

Objective  To determine if final intraoperative parathyroid hormone (IOPTH) level predicts those at risk for recurrence after parathyroidectomy. Minimally invasive parathyroid exploration guided by preoperative imaging and IOPTH level is an accepted alternative to bilateral exploration for the treatment of primary hyperparathyroidism (HPT). However, additional enlarged, hypercellular parathyroid glands are present in some patients in whom IOPTH levels fall to normal after excision of a single adenoma. At least 15% of patients are normocalcemic with elevated PTH levels (PPTH) after parathyroidectomy. In these patients, a higher risk of recurrent HPT has been found.

Design  Retrospective review of medical records.

Setting  University teaching hospital.

Patients  The records of all 194 patients who underwent successful initial parathyroidectomy for nonfamilial HPT in 2007 and 2008 by 1 surgeon were reviewed.

Main Outcome Measures  Intraoperative PTH level was measured prior to incision (baseline); at excision of the abnormal gland; at 5, 10, 15, and 20 minutes after excision; and at various additional times as needed. Of the patients, 71% underwent minimally invasive parathyroid exploration. Calcium, PTH, and 25-hydroxyvitamin D levels were measured during the first month after surgery in all patients and after 3 months or more in 80%. Patients were divided into 5 groups depending on the following final IOPTH levels: lower than 10 pg/mL (group l) (to convert PTH to nanograms per liter, multiply by 1.0); 10 to 19 pg/mL (group 2); 20 to 29 pg/mL (group 3); 30 to 39 pg/mL (group 4); and 40 pg/mL or higher (group 5).

Results  Of the patients, 82% had a single adenoma, 9% had double adenomas, and 9% had 3 or more abnormal glands. The final IOPTH/baseline IOPTH value in groups 1 to 5 was 7%, 11%, 16%, 23%, and 26%, respectively. There was no significant difference in the preoperative calcium among the groups. All 3 patients with persistent HPT and 5 patients with PPTH were in group 5. One of the 96 patients in groups 1 and 2 and 5 of the 72 patients in groups 3 and 4 had PPTH at the last evaluation.

Conclusion  Patients with a final IOPTH level of 40 pg/mL or higher are at higher risk of having persistent HPT and should be followed up closely and indefinitely following parathyroidectomy.

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Minimally Invasive Parathyroidectomy: Use of Intraoperative Parathyroid Hormone Assays After 2 Preoperative Localization Studies [Original Article]

Objectives  To review minimally invasive parathyroidectomy (MIP) in patients undergoing initial surgical management of primary hyperparathyroidism (HPT) with preoperative, localizing sestamibi scanning (MIBI), and concordant ultrasonography (US) to determine if intraoperative parathyroid hormone (iPTH) is necessary in these cases. Minimally invasive parathyroidectomy has become an acceptable therapeutic option in treating primary HPT. Preoperative MIBI scanning, high-resolution US with color Doppler flow, and iPTH monitoring have refined this technique.

Design  Retrospective review.

Patients  The medical records of 738 consecutive patients who had undergone surgery for HPT. After excluding revision surgical procedures, secondary and tertiary HPT, unavailable intraoperative parathyroid (PTH) data, concomitant thyroid disease requiring thyroidectomy, and patients without preoperative MIBI or US, 428 patients (58%) were included in the study.

Results  The mean decrease in PTH level was 85%. Of the 428 patients with primary HPT included in the study, 209 patients (49%) had localizing, concordant preoperative MIBI and US. A decline of more than 50% in iPTH levels was observed in 202 patients (97%) after removal of parathyroid tissue localized by MIBI and US. The procedures for 4 patients were converted to bilateral neck explorations after the postexcision PTH level failed to drop less than 50%.

Conclusions  Our results show that iPTH monitoring may be eliminated in MIP surgery in a carefully selected group of patients who have preoperative, localizing MIBI with concordant US. This potentially allows an increase in operating room efficiency and a decrease in costs while performing MIP.

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N2 Disease in Patients With Head and Neck Squamous Cell Cancer Treated With Chemoradiotherapy: Is There a Role for Posttreatment Neck Dissection? [Original Article]

Objectives  To determine whether nodal necrosis and node size of 3 cm or larger are risk factors for recurrent neck disease and whether negative computed tomography–positron emission tomography (CT-PET) results 8 weeks or more after therapy indicate complete response in the neck in patients with N2 disease.

Design  Retrospective study.

Setting  State university hospital.

Patients  Fifty-six patients with head and neck squamous cell cancer and N2 disease treated with chemoradiotherapy were evaluated for persistent or recurrent neck disease. Tumor characteristics analyzed were primary site, T category, nodal size (<3 cm or ≥3 cm), nodal necrosis based on hypodensity of one-third or more of the node, and type of N2 disease (N2a, N2b, or N2c). Forty-eight of the 56 patients underwent CT-PET to determine treatment response after chemoradiotherapy. Clinical examination, imaging, and pathologic specimens were used to confirm disease recurrence.

Main Outcome Measures  The number of recurrence events, disease-free interval, and positive posttreatment CT-PET result in the neck.

Results  Most patients had oropharyngeal tumors (n = 37; 66%), T2 tumors (n = 21; 38%), nodes 3 cm or larger (n = 43; 77%), positive necrosis (n = 40; 71%), and N2c disease (n = 28; 50%). Multivariate analysis determined that no factors were significant predictors of recurrence, except for positive posttreatment PET results (P < .001). Comparison of CT-PET with nodal recurrence demonstrated a sensitivity of 82%, a specificity of 97%, a negative predictive value of 95%, and a positive predictive value of 90%.

Conclusion  Posttreatment neck dissections may not be indicated for patients with N2 disease and a negative CT-PET result, even in patients with nodal necrosis and nodes 3 cm or larger.

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Early Prediction of Response to Chemoradiotherapy for Head and Neck Cancer: Reliability of Restaging With Combined Positron Emission Tomography and Computed Tomography [Original Article]

Objective  To assess the role of combined positron emission tomography and computed tomography (PET-CT) in predicting early treatment response at the primary site and in the neck after chemoradiotherapy (CRT) for advanced squamous cell carcinoma of the head and neck (SCCHN).

Design  Retrospective analysis with a median follow-up of 24 months.

Setting  Academic, tertiary referral center.

Patients and Interventions  Thirty-one patients who were treated with concomitant intra-arterial CRT underwent PET-CT 6 to 8 weeks after the completion of treatment. Patients with findings on the physical examination, CT, or PET-CT indicative of persistent disease underwent appropriate surgical intervention for pathological assessment. Patients with a complete clinical response were observed with routine follow-up physical examination for disease recurrence. No evidence of disease at least 6 months after the completion of PET-CT was considered confirmation of complete clinical response.

Main Outcome Measures  Presence or absence of residual or recurrent disease during the follow-up period was used to calculate the sensitivity, specificity, and positive and negative predictive values of PET-CT for the primary site and the neck.

Results  Assessment of tumor response at the primary site with PET-CT had a sensitivity, specificity, and positive and negative predictive values of 83%, 54%, 31%, and 92%, respectively. In patients with pretreatment N1 to N3 disease, the sensitivity, specificity, and positive and negative predictive values of posttreatment PET-CT were 75%, more than 94%, more than 75%, and 94%, respectively, and the specificity and negative predictive value for patients with pretreatment N0 disease in the neck were 92% and more than 92%, respectively.

Conclusions  Negative PET-CT findings accurately determine early disease response at the primary site and in the neck. False-positive findings are common at the primary site. Patients with a negative PET-CT finding after the completion of intra-arterial CRT do not require surgical intervention.

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Predicting Residual Neck Disease in Patients With Oropharyngeal Squamous Cell Carcinoma Treated With Radiation Therapy: Utility of p16 Status [Original Article]

Objective  To identify factors that predict complete response of cervical nodal disease to radiation therapy (RT) in patients with oropharyngeal squamous cell carcinoma (OP-SCCA).

Design  Histologic analysis of prospectively collected specimens and retrospective medical chart review.

Setting  Tertiary referral center.

Subjects  Sixty-nine patients with OP-SCCA treated from January 1, 2002, through June 1, 2008.

Intervention  Definitive RT, with or without chemotherapy and with or without neck dissection (ND).

Main Outcome Measure  Presence of a viable tumor in post-RT ND specimen.

Results  Tissue specimens from 69 patients with OP-SCCA treated primarily with RT, with or without chemotherapy, were evaluated. Of these, 47 (68.1%) were strongly and diffusely positive for p16 expression by immunohistochemical analysis, signifying human papillomavirus positivity. Patients with p16-positive and p16-negative tumors (hereinafter, p16+ and p16–, respectively) had similarly sized primary tumors on presentation, but p16+ primary tumors were associated with more advanced neck disease (nodal stages N2c-N3; 31.9% vs 4.5% for p16– tumors) and more contralateral nodes (27.7% vs 4.5% for p16– tumors). Forty-seven patients (59.0%) underwent planned posttreatment ND (a total of 55 NDs). The NDs performed for p16– tumors were significantly more likely to have viable tumor in the specimen (50.0% vs 18.0% for p16+ tumors; P  = .02). In addition, p16+ necks with residual viable cancer were characterized by incomplete response on post-RT imaging, tobacco and alcohol use, and extracapsular spread on pretreatment imaging.

Conclusions  In conjunction with other clinical parameters, p16 status can help predict the need for post-RT ND in patients with OP-SCCA. Although close observation may be warranted in selected patients with p16+ tumors, patients with p16– tumors are at much higher risk for residual neck disease, even when initial nodal disease is less advanced.

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Error in Figure in: Oropharyngoplasty With Template-Based Reconstruction of Oropharynx Defects [Correction]

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Neck Response to Chemoradiotherapy: Complete Radiographic Response Correlates With Pathologic Complete Response in Locoregionally Advanced Head and Neck Cancer [Original Article]

Objective  The role of neck dissection following chemoradiotherapy (CRT) for locoregionally advanced head and neck cancer is an area of active debate. Patients who have a complete radiographic response may not need dissection, and the extent of neck dissection necessary for those patients with residual disease is unclear.

Design  Retrospective review of data from a prospectively collected database of patients with locoregionally advanced head and neck cancer treated as part of a phase 2 study of induction chemotherapy followed by concurrent CRT. The results of post-CRT neck computed tomography (CT) imaging and pathologic analysis of the neck dissection specimens were compared to evaluate correlation between radiographic and pathologic response.

Results  Forty-nine patients underwent 61 hemineck dissections. Overall, 209 neck levels were dissected. Radiologic complete response in the neck was achieved in 39 patients, all of whom had pathologic specimens negative for tumor cells. Ten patients (20%) had a total of 14 neck levels with residual disease on CT imaging. Five (50%) of these 10 patients were found to have residual tumor cells on pathologic analysis. Tumor cells were contained only to those levels found positive on CT imaging; they were present in 7 (50%) of the 14 positive levels.

Conclusions  Neck levels with residual disease on post-CRT CT imaging warrant removal. However, neck levels without evidence of disease on post-CRT CT imaging are unlikely to harbor cancer, which lends further support to the concept of basing neck dissection on post-CRT staging and performance of limited neck dissections for patients with limited residual disease.

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Error in Text in: Comparison of Clinical and Pathological Staging in Head and Neck Squamous Cell Carcinoma: Results From Intergroup Study ECOG 4393/RTOG 9614 [Correction]

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Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus-Related Head and Neck Cancer [Original Article]

Background  Human papillomavirus (HPV) is the most identifiable cause of head and neck squamous cell cancer (HNSCC). Compared with HPV-negative HNSCC, HPV-positive HNSCC presents at an advanced stage but with significantly better survival. We created a syngeneic mouse model of HPV-positive and HPV-negative HNSCC by transforming mouse primary tonsil epithelial cells with either HPV oncogenes or a nonantigenic RNA interference strategy that affects similar oncogenic pathways.

Objectives  To examine the effect of radiation therapy on HPV-positive and HPV-negative tumors in immune-competent and immune-incompetent mice and to examine responses in human cancer cell lines.

Design  Prospective in vivo murine model.

Main Outcome Measures  Survival and tumor growth.

Results  For human and murine transformed cell lines, HPV-positive cells were more resistant to radiation and cisplatin therapy compared with HPV-negative cells. In vivo, HPV-positive tumors were more sensitive to radiation, with complete clearance at 20 Gy, compared with their HPV-negative counterparts, which showed persistent growth. Cisplatin in vivo cleared HPV-positive tumors but not HPV-negative tumors. However, neither radiation or cisplatin therapy cured immune-incompetent mice. Adoptive transfer of wild-type immune cells into immune-incompetent mice restored HPV-positive tumor clearance with cisplatin therapy.

Conclusions  The HPV-positive tumors are not more curable based on increased epithelial sensitivity to cisplatin or radiation therapy. Instead, radiation and cisplatin induce an immune response to this antigenic cancer. The implications of these results may lead to novel therapies that enhance tumor eradication for HPV-positive cancers.

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A 25-Year Analysis of Veterans Treated for Tonsillar Squamous Cell Carcinoma [Original Article]

Objective  To determine the recurrence and survival outcome based on treatment date, type of treatment, stage of disease, and comorbidity and the recurrence and survival differences based on smoking status as a surrogate for human papillomavirus status in veterans treated for tonsillar squamous cell carcinoma (SCC).

Design  Outcome cohort study.

Setting  Tertiary care Department of Veterans Affairs hospital.

Patients  A consecutive sample from 1981 through 2006 of 683 patients treated for oropharyngeal SCC was screened, and 141 patients with tonsillar SCC without distant metastatic spread and a minimum of 2 years of follow-up were included.

Main Outcome Measures  Disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).

Results  Disease-free survival was significantly better in cohort II (treated during or after 1997) compared with cohort I (treated before 1997) (2- and 5-year DFS, 82% vs 64% and 67% vs 48%; P = .02). Disease-specific survival was better in the surgical vs nonsurgical group (2- and 5-year DSS, 77% vs 46% and 67% vs 30%; P < .001), as was the OS (2- and 5-year OS, 66% vs 41% and 45% vs 23%; P = .005). In subjects with early-stage disease, OS and DSS were not different regardless of treatment type. In subjects with late-stage disease treated most recently (time cohort II), there was significantly better DSS in those receiving surgical vs nonsurgical treatment (2-year DSS, 70% vs 43%; P = .045). Nonsmokers had better OS (94 months vs 41 months; P = .001) and lower incidence of recurrence (8% vs 44%; P = .02).

Conclusion  In veterans treated for tonsillar SCC, we advocate the consideration of a treatment plan that includes surgery for patients presenting with advanced-stage SCC of the tonsil, even in patients with notable comorbidities.

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Factors That Predict Postoperative Pulmonary Complications After Supracricoid Partial Laryngectomy [Original Article]

Objective  To determine the risk factors related to postoperative pulmonary complications in patients who undergo supracricoid partial laryngectomy.

Design  Retrospective analysis of medical records.

Setting  Tertiary care referral center.

Patients  One hundred eleven patients who underwent supracricoid partial laryngectomy from January 1, 1993, through December 31, 2008.

Main Outcome Measures  Relationship between postoperative pulmonary complications and perioperative risk factors, such as age, sex, chronic lung disease, smoking status, tumor site, tumor stage, preoperative irradiation, extent of surgery, reconstruction method, and pulmonary function tests.

Results  Thirty-six patients (32.4%) developed postoperative pulmonary complications. Significant correlations were found among age (P = .002), chronic lung disease (P = .005), smoking status (P = .02), and postoperative pulmonary complications. Cricohyoidopexy (P = .008) and ipsilateral arytenoidectomy (P = .03) were associated with postoperative pulmonary complications. The multivariate analysis showed a significant association of the postoperative pulmonary complications with age (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.2-11.7 in patients 60 to 69 years old; and OR, 7.1; 95% CI, 1.3-37.6 in patients 70 to 79 years old) and cricohyoidopexy (OR, 4.4; 95% CI, 1.1-18.1).

Conclusion  Patients 60 years or older and patients with cricohyoidopexy are at high risk of having postoperative pulmonary complications after supracricoid partial laryngectomy.

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Postoperative Reirradiation for Mucosal Head and Neck Squamous Cell Carcinomas [Original Article]

Objectives  To compare toxic effects and functional outcomes of reirradiation with and without salvage surgery for nonnasopharyngeal mucosal head and neck squamous cell carcinoma.

Design  Retrospective review.

Setting  Academic tertiary referral hospital.

Patients  Between December 1992 and March 2007, a total of 87 patients underwent reirradiation (64 for cure and 23 for palliation).

Intervention  Patients underwent reirradiation with (n = 38) or without salvage surgery (n = 49). After January 2000 there was increased use of concurrent platinum-based chemotherapy (80% vs 5%) and intensity-modulated radiation therapy (82% vs 0%).

Main Outcome Measures  Early and late toxic effects of treatment by Radiation Therapy Oncology Group criteria, tracheostomy retention, gastrostomy tube dependence, and survival.

Results  The median follow-up among patients alive at last contact was 5.0 years. Compared with reirradiation without surgery, postoperative reirradiation was associated with increased early grade 3 to grade 5 toxic effects (50% [19 of 38] vs 29% [14 of 49], P = .04) and with longer median survival (17.3 vs 8.9 months, P < .001). Free-flap reconstruction decreased early toxic effects in the surgical cohort by 16% (from 60% [9 of 15] to 43% [10 of 23], P = .32). Gastrostomy tube dependence (P = .05) and tracheostomy retention (P = .04) have increased since 2000. The median survival for curative patients was 12.5 months. The estimated 2-year survival was 25%, and the estimated 5-year survival was 8%.

Conclusions  Reirradiation represents the only chance for cure in patients with unresectable disease. After surgery, reirradiation is performed in patients at high risk of locoregional recurrence and may increase acute toxic effects. However, free-flap reconstruction may reduce toxic effects. Functional outcomes have declined since 2000 likely because of the addition of concurrent platinum-based chemotherapy. Future research may define the subpopulation of postoperative patients for whom survival benefits most outweigh reirradiation toxic effects.

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Complications That Affect Postlaryngectomy Voice Restoration: Primary Surgery vs Salvage Surgery [Original Article]

Objective  To assess the effect of primary treatment on tracheoesophageal voice prosthesis (TEP) complications.

Design  Retrospective cohort study.

Setting  The Johns Hopkins Medical Institutions, Baltimore, Maryland.

Patients  Patients who underwent total laryngectomy and TEP between January 1, 1998, and December 31, 2008, were divided into 3 subgroups according to primary treatment: surgery (n = 81), radiotherapy (n = 61), and chemoradiotherapy (n = 32).

Main Outcome Measures  Number of weeks before leakage through the TEP, occurrence of leakage around the TEP, TEP dislodgement, and size changes 6 months or longer after laryngectomy.

Results  A total of 174 patients met the study criteria. Of the 81 patients who underwent primary surgery, 81% (n = 66) underwent adjuvant therapy with postoperative radiotherapy or chemoradiotherapy. The incidence of leakage around the prosthesis, prosthesis dislodgement, and size changes 6 months or longer after laryngectomy were significantly higher for patients who required salvage total laryngectomy after chemoradiotherapy or radiotherapy (P < .05). In addition, significantly more patients who underwent salvage total laryngectomy required extended laryngectomy or free tissue reconstruction.

Conclusions  Voice prosthesis complications are more frequently encountered in those who require salvage laryngectomy. Understanding the potential for such complications reinforces the need for close communication and follow-up with these patients by the speech language pathologist.

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