Expert Consensus Statement: Pediatric Drug-Induced Sleep Endoscopy.

OBJECTIVE: To develop an expert consensus statement on pediatric drug-induced sleep endoscopy (DISE) that clarifies controversies and offers opportunities for quality improvement. Pediatric DISE was defined as flexible endoscopy to examine the upper airway of a child with obstructive sleep apnea who is sedated and asleep. METHODS: Development group members with expertise in pediatric DISE followed established guidelines for developing consensus statements. A search strategist systematically reviewed the literature, and the best available evidence was used to compose consensus statements regarding DISE in children 0 to 18 years old. Topics with significant practice variation and those that would improve the quality of patient care were prioritized. RESULTS: The development group identified 59 candidate consensus statements, based on 50 initial proposed topics, that focused on addressing the following high-yield topics: (1) indications and utility, (2) protocol, (3) optimal sedation, (4) grading and interpretation, (5) complications and safety, and (6) outcomes for DISE-directed surgery. After 2 iterations of the Delphi survey and removal of duplicative statements, 26 statements met the criteria for consensus; 11 statements were designated as no consensus. Several areas, such as the role of DISE at the time of adenotonsillectomy, were identified as needing further research. CONCLUSION: Expert consensus was achieved for 26 statements pertaining to indications, protocol, and outcomes for pediatric DISE. Clinicians can use these statements to improve quality of care, inform policy and protocols, and identify areas of uncertainty. Future research, ideally randomized controlled trials, is warranted to address additional controversies related to pediatric DISE.

Multi-institutional Evaluation of Radiologic Findings Associated With Pediatric Congenital Idiopathic Bilateral Vocal Fold Dysfunction.

OBJECTIVE: To report brain magnetic resonance imaging (MRI) and ultrasonography findings in pediatric patients with congenital idiopathic bilateral vocal fold dysfunction and analyze factors associated with its etiology and resolution. STUDY DESIGN: Case series with retrospective review. SETTING: Tertiary care multi-institutional setting: Nationwide Children's Hospital, Indiana University, University of North Carolina, and Cleveland Clinic. METHODS: Pediatric patients with congenital idiopathic bilateral vocal fold dysfunction were included in this review. RESULTS: Congenital idiopathic bilateral vocal fold dysfunction was identified in 74 patients from 2000 to 2018. Brain MRI scans were performed in all patients and ultrasonography in 30 (40.5%). Normal imaging results were most commonly found in patients born full-term (P < .0001) or via vaginal delivery (P < .01). Abnormal brain MRI and ultrasound results were found in 38 of 74 (51.3%) and 16 of 30 (53.3%), respectively. Type I Chiari malformation was not identified in any patient. No specific brain MRI or ultrasound abnormality was associated with patients' bilateral vocal fold dysfunction. Complete/incomplete bilateral vocal fold resolution occurred in 45 of 74 (60.8%) patients over the study interval and was not associated with brain MRI or ultrasound findings or birth complications but was associated with vaginal delivery (P = .02). Resolution rates were highest for patients with bilateral vocal fold paramedian paralysis (P = .05). CONCLUSIONS: In this multi-institutional study, no specific brain MRI or ultrasound abnormality was associated with patients' bilateral vocal fold dysfunction or subsequent resolution rates. While imaging is often performed to detect and treat any reversible causes of bilateral vocal fold dysfunction, in this series, imaging findings were heterogeneous and did not identify any treatable causes, such as type I Chiari malformation.

Utility of polysomnography and video swallow studies in the management of pediatric patients with congenital idiopathic bilateral vocal fold dysfunction.

OBJECTIVES: Congenital idiopathic bilateral vocal fold dysfunction (BVFD) is an uncommon cause of neonatal stridor and respiratory distress postnatally. Approximately 50% of affected neonates or infants will historically require tracheostomy for this condition. Timing and candidacy for tracheostomy in BVFD patients is often subjective and poorly understood. Polysomnography (PSG) and video swallow studies (VSS) may be helpful in the management of patients with BVFD prior to tracheostomy by quantifying their degree of upper airway obstruction during sleep and feeding dysfunction while awake. METHODS: We performed a single-institution retrospective case series of BVFD patients from 2000 to 2018 who had postnatal PSGs performed prior to tracheostomy. Demographics, gestational age, and VSS results prior to PSG were recorded for all patients. Findings from PSGs included non-REM AHI, REM AHI, oxygen nadir, % total sleep time (TST) O2<90%, peak end-tidal (ET) CO2, % TST ETCO2 >52 torr. Rates of post-PSG tracheostomy, gastrostomy tube (G-tube) placement, and home O2 supplementation were noted for all patients. RESULTS: From 2000 to 2018, 12/46 (26%) BVFD patients had postnatal PSGs performed prior to tracheostomy. Median patient age at BVFD diagnosis, VSS, and PSG was 5.5 days, 12.5 days, and 17.5 days, respectively. Mild, moderate, and severe obstructive sleep apnea (OSA) was found in 7/12, 3/12, and 4/12 patients, respectively. Hypercapnia (ETCO2 >52 torr) was found in 5/12 patients on PSG while hypoxemia (SpO2 <90% for >4% TST) was not found in any patient. VSS results demonstrated normal swallowing, inconsistent laryngeal penetration, and silent aspiration in 7/12, 2/12, and 3/12 patients, respectively. Tracheostomy and G-tube placement was performed in 3/12 and 2/12 patients, respectively. There was no association between the severity of OSA or any PSG abnormality, VSS findings, and the performance of tracheostomy in any BVFD patient. CONCLUSIONS: OSA was found in all BVFD patients undergoing postnatal PSG at our institution while feeding dysfunction was found in approximately 50% of patients. The presence of feeding dysfunction, severe OSA, or any PSG abnormality was not individually associated with the subsequent performance of a tracheostomy in our patients. PSG is likely useful in supporting but not supplanting one's clinical decision-making in the management of patients with congenital idiopathic BVFD.

Radiologic, genetic, and endocrine findings in isolated congenital nasal pyriform aperture stenosis patients.

BACKGROUND: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of upper airway obstruction in neonates. It can occur either associated with a solitary median maxillary central incisor (SMMCI) in 40-75% of cases or as an isolated morphogenic variant. Brain MRI is routinely performed in patients with CNPAS with a SCMMI due to the concomitant risks of intracranial midline defects of the hypothalamic-pituitary axis (HPA), holoprosencephaly, or associated endocrine dysfunction. However, the role of routine brain imaging and endocrinologic evaluation in patients with isolated CNPAS is not frequently studied given the assumption that isolated CNPAS is unlikely to be associated with any intracranial findings. OBJECTIVES: To evaluate intracranial findings on dual brain MRI imaging in isolated CNPAS patients and to determine if any radiologic, endocrinologic, or genetic abnormalities existed in these patients. METHODS: We performed a single-institution retrospective review and case series of patients with isolated CNPAS from 2006 to 2019. Findings from dual brain MRI imaging, cytogenetic and karyotype testing, and formal endocrinologic testing were analyzed for each patient and compared to reported findings in isolated CNPAS patients within the literature. RESULTS: From 2006 to 2019, 16/29 patients were identified at our institution with isolated CNPAS. Inpatient otolaryngologic consultation, CT, and brain MRI imaging was obtained after a mean postnatal age of 3.21 days, 13.5 days, and 35.91 days, respectively. Dual brain MRI imaging was obtained in 12/16 (75%) patients. In our patients, abnormal MRI findings included hypothalamic hamartoma, pars intermedius cyst, and grades 1 and 4 germinal matrix hemorrhages. No holoprosencephaly was found in any patient. Genetic testing was performed on 10/16 (62.5%) patients. Karyotyping was normal in all patients and microarray testing was abnormal in 2/10 patients that represented a 2p16.3 deletion in one patient and a 7q36 deletion causing an unbalanced translocation mutation of the Sonic Hedgehog gene in the second patient. In the latter patient, a hypothalamic hamartoma and panhypopituitarism was found. Endocrine evaluation was performed in 5 patients and was normal in 3/5 patients. CONCLUSIONS: Our case series of isolated CNPAS patients identified multiple abnormalities on radiologic, genetic, and endocrine testing; one of which that involved a defect of the HPA with panhypopituitarism resulting from a hypothalamic hamartoma. Based upon our findings, dedicated brain MRI imaging, endocrinologic, and genetic testing, should likely be considered for any newly diagnosed, isolated CNPAS patient given the uncommon but potential risk for associated intracranial abnormalities.

Improving Communication Delay of Outpatient Sleep Study Results to Pediatric Otolaryngology Patients and Families.

OBJECTIVE: We undertook this quality improvement project to improve communication of outpatient pediatric sleep study results to families in a consistent and timely manner. METHODS: Based on the Institute for Healthcare Improvement quality improvement methodology, multiple key drivers were identified, including standardizing documentation and communication for sleep study results among the otolaryngology department, sleep center, and families. Meaningful interventions included developing standard electronic medical record documentation and utilizing otolaryngology nurses and advanced practice nurses to assist with communication by sending the results from the sleep center to both the referring otolaryngology provider and the triage nurses. The primary outcome measure was the monthly proportion of sleep studies communicated by the otolaryngology department to families within 3 business days. RESULTS: Average monthly sleep study results communicated to families within 3 business days increased from 31% to 92.9% over the study period ( P < .0001). Sleep study results were personally communicated via telephone and voicemail in 60.88% and 34.0% of cases, respectively. Approximately 50.0% of families receiving voicemails later contacted our department for their children's study results. DISCUSSION: Novel documentation strategies and involvement of our entire clinical team (physicians, nurses, and advanced practice nurses), allowed us to significantly improve the consistency and timeliness of our communication of outpatient sleep study results to families in a proactive manner. IMPLICATIONS FOR PRACTICE: With time-sensitive clinical test results, such as those from pediatric sleep studies, intra- and interdepartmental collaboration and standardization of the communication process and documentation may allow for more expedient care of children with suspected obstructive sleep apnea.

Interventions to Improve Response Time to Nurse Triage Phone Calls in a Tertiary Care Pediatric Otolaryngology Practice.

Importance: Delay in response for telephone triage calls that need clinician input for resolution can result in delay of care and unintended frustration for patients and families. It can be a challenge to manage calls in a high-volume pediatric otolaryngology practice. Objective: To improve the percentage of nurse triage clinically relevant phone calls returned within 2 hours to parents or caregivers. Design, Setting, and Participants: This was a quality-improvement study of a tertiary care pediatric otolaryngology practice with more than 32 000 clinic visits and more than 9000 surgical patients per year. Interventions: In 2014, a collaborative team was created at our center to determine the optimal time for triage callback to families and to define an optimal process that would allow more rapid response time for calls that the triage nurses needed to escalate to the patient's managing surgeon. Several plan-do-study-act cycles were performed to optimize the process. The utilization of advanced practice nurses as an intermediary step was crucial in allowing a more efficient flow of communication. Main Outcomes and Measures: Percentage of triage phone calls returned within 2-hour time frame. Results: Over 40 months, 4839 clinically relevant phone calls occurred, averaging 128 calls per month. The baseline mean was 101 calls per month, and the postintervention mean was 130 calls per month. Prior to this project, only 42% of calls were being addressed within 2 hours. After our interventions, the average time for caregiver callback within 2 hours decreased from 15.3 hours preintervention to 3.9 hours postintervention. In addition, caregivers received clinician callback within 2.0 hours 76.7% of the time postintervention compared with 42.0% with a baseline shift (difference probability between preintervention and postintervention, 0.21; 95% CI, 0.15-0.27). Outcomes were sustained for 3 years and continue to be monitored. Conclusions and Relevance: The most effective intervention was using advanced practice nurses to efficiently resolve patient triage concerns that were outside the scope of practice of the registered nurse. By establishing clear pathways of communication and standardized education among our team, we successfully improved our processes, which resulted in more optimal care for our patients.

Postoperative bradycardia following adenotonsillectomy in children: Does intraoperative administration of dexmedetomidine play a role?

INTRODUCTION: Dexmedetomidine is a novel pharmacologic agent that has become a frequently used adjunct during care of pediatric patients with obstructive sleep apnea (OSA) undergoing tonsillectomy. While generally safe and effective, dexmedetomidine is associated with adverse effects of hypotension and bradycardia from its central sympatholytic effects. Due to safety concerns, our institution routinely admits patients with OSA for overnight cardiorespiratory monitoring following tonsillectomy. With such monitoring, we have anecdotally noted bradycardia in our patients and sought to investigate whether this was related to the increased use of intra-operative dexmedetomidine. METHODS: We retrospectively reviewed records over an 11-month period to compare the incidence of postoperative bradycardia following hospital admission for tonsillectomy in patients who received dexmedetomidine versus those who did not. RESULTS: The study cohort included 921 patients (371 received dexmedetomidine and 550 did not). Bradycardia was asymptomatically noted in 66 patients (7.2%). No patient required medical intervention for the bradycardia or developed clinical symptoms. There was no association of bradycardia with the intra-operative administration of dexmedetomidine (8.9% of patients who received dexmetomidine vs. 9.4% who did not). In multivariable analysis, bradycardia was more common among older patients, with the administration of topical or injected lidocaine, and with specific associated procedures (inferior turbinate coblation with out-fracture or direct laryngoscopy and bronchoscopy). CONCLUSION: The increased incidence of asymptomatic bradycardia in our post-adenotonsillectomy patients seemed to relate more to increased utilization of postoperative cardiac telemetry, and did not appear associated with the use of dexmedetomidine use intra-operatively.

Changes in intracuff pressure of cuffed endotracheal tubes while positioning for adenotonsillectomy in children.

BACKGROUND: When using cuffed endotracheal tubes (cETTs), changes in head and neck position can lead to changes in intracuff pressure. AIM: The aim of this study was to assess the combined effect of neck extension, shoulder roll placement, and Crowe-Davis retractor use during adenotonsillectomy on the intracuff pressure of cETTs in children. METHODS: Patients <18 years of age undergoing adenotonsillectomy under general anesthesia following the placement of a cETT were included in the study. After inflation of the cuff to seal the trachea, using the leak test, baseline intracuff pressure was recorded and then continuously monitored. After neck extension, placement of a shoulder roll, insertion of the Crow-Davis retractor, suspension from a Mayo stand, and positioning for surgery, the intracuff pressure was recorded again. RESULTS: The study cohort included 84 patients, ranging in age from 0.9 to 17 years (5.7 ± 3.9 years). In 46 patients (54.8%), the intracuff pressure increased from baseline after positioning for adenotonsillectomy. In 12 of these patients (14.3%), the intracuff pressure was >30 cm H2O. The intracuff pressure decreased in 28 patients (33.3%), while no change was noted in 10 patients (11.9%). Overall, the general trend was an increase in intracuff pressure from 15.9 ± 7.8 cm H2O to 18.9 ± 11.6 cm H2O. CONCLUSION: Both increases and decreases in the intracuff pressure may occur following positioning of the pediatric patient for adenotonsillectomy. An increase in intracuff pressure may result in a higher risk of damage to the tracheal mucosa. A decrease in the intracuff pressure can result in an air leak resulting in inadequate ventilation, increased risk of aspiration, and even predispose to airway fire if oxygen-enriched gases are used. Continuous intracuff pressure monitoring or rechecking the intracuff pressure after positioning for adenotonsillectomy may be indicated.

Sevoflurane and bradycardia in infants with trisomy 21: A case report and review of the literature.

Various perioperative concerns have been reported in patients with trisomy 21 including associated congenital heart disease, atlantoaxial instability, tracheal and subglottic stenosis, a predisposition to respiratory complications, hypothyroidism, and macroglossia leading to sleep disordered breathing. The recent literature has also suggested a propensity for the development of significant bradycardia during inhalation induction with sevoflurane. We present a 2-year-old girl with trisomy 21 who developed the rapid onset of bradycardia during anesthetic induction with sevoflurane. Previous reports are reviewed, postulated mechanisms discussed, and preventative strategies presented.

Plastic bronchitis arising from solitary influenza B infection: A report of two cases in children.

Plastic bronchitis (PB) is characterized by thick, inspissated, tracheobronchial casts. It is classified as either inflammatory or acellular based on the content of the endobronchial casts. PB has never been reported in a healthy child with solitary influenza B infection. This study is a retrospective case series of two children who presented to our institution in acute respiratory distress. Emergency rigid bronchoscopy was performed with extraction of casts from the L mainstem bronchus in both patients. Influenza B was the only isolate identified. In otherwise healthy children with respiratory distress, influenza B-mediated inflammatory PB must be considered in the differential diagnosis.

Short- and long-term outcomes after silastic medicalization laryngoplasty: are arytenoid procedures needed?

OBJECTIVE: To evaluate short- and long-term vocal outcomes after medialization laryngoplasty (ML) using a silastic implant in patients with unilateral vocal fold paralysis (UVFP). DESIGN AND METHODS: Prospective study of consecutive patients undergoing ML with silastic (MLS) diagnosed with UVFP from 2009 till 2012 and with at least 9 months follow-up. Pre- and post-treatment maximum phonation time (MPT) and voice handicap index (VHI) scores were compared to assess the impact of ML on these outcomes. Patients with high vagal lesions or lateralized vocal folds (very low MPT) were compared with the entire group and the literature. RESULTS: A total of 124 patients with UVFP underwent MLS. Forty-six patients were excluded as they either had a Gore-Tex implant (eight), short follow-up (20), or the primary case was a revision (18). Seventy-eight patients were included. Pretreatment mean VHI (total score) was 67 for the entire cohort. Postoperative VHI score was significantly lower both in short-term (3-8 weeks) follow-up, mean score 27 (paired t-test, P < 0.05) and in long-term follow-up (9-12 months), mean score 22 (P < 0.05). MPT was significantly improved from 8.3 pretreatment to 22.6 at short-term follow-up (P < 0.05) and to 24.2 long-term follow-up (P < 0.05). There were no significant differences between entire cohort and patients with a lateralized vocal fold or high vagal lesion. Comparable results were present when compared with the literature using similar metrics in patients undergoing an arytenoid procedure with/without medialization. CONCLUSION: MLS alone is effective in managing UVFP in most patients.

A technique to measure the intracuff pressure continuously: an in vivo demonstration of its accuracy.

OBJECTIVE: A major concern with the use of cuffed endotracheal tubes (cETT) in children is hyperinflation of the cuff which may compromise tracheal mucosal perfusion. To measure the intracuff pressure (CP), we devised a method using the transducer of an invasive pressure monitoring device. The objective of the study was to test the accuracy and validity of this device for instantaneous and continuous CP monitoring. METHODS: The study was conducted in 2 phases. In Phase 1 (200 pediatric patients), after inflation of the cuff, the CP was measured using the standard manometer and the transducer simultaneously. In Phase 2 (20 pediatric patients), the transducer was left connected to the pilot balloon of the ETT to obtain a continuous CP reading and the standard manometer was used to measure the CP at 5-min intervals. Statistical analysis included a Bland-Altman comparison and linear regression analysis. RESULTS: In Phase 1, linear regression analysis demonstrated an R2 value of 0.9956. The bias was 0.30 cmH2O, the precision was 0.75 cmH2O, and the 95% level of agreement (LOA) ranged from -1.16 to 1.77 cmH2O. In Phase 2, the linear regression analysis revealed an R2 value of 0.9846. The bias was 0.28 cmH2O, the precision was 0.7 cmH2O, and the 95% LOA ranged from -1.1 to 1.66 cmH2O. CONCLUSION: Our study demonstrates that when cETTs are used in the pediatric population, the transducer of the invasive pressure monitoring device can be used reliably to measure the CP at the time of inflation and continuously thereafter.

The relationship between head and neck position and endotracheal tube intracuff pressure in the pediatric population.

BACKGROUND: Over the past few years, there has been a change in clinical practice with a transition to the use of cuffed instead of uncuffed endotracheal tubes (ETTs) in pediatric patients. These changes have led to concerns regarding unsafe intracuff pressures in pediatric patients, which may result in postoperative morbidity. To avoid these issues, it is generally suggested that the intracuff pressure be maintained at ≤30 cmH2 O. The current study prospectively assesses the changes in intracuff pressure related to alterations in head and neck position in pediatric patients. METHODS: Patients less than 18 years of age, undergoing surgery, requiring endotracheal intubation with a cuffed ETT were eligible for inclusion. No alteration in the technique of anesthetic induction or maintenance was required for the study. Following endotracheal intubation and inflation of the cuff with the head and neck in a neutral position, the intracuff pressure was measured. The intracuff pressure was then subsequently measured with the head turned to the right, head turned to the left, head and neck flexed, and head and neck extended. RESULTS: A total of 200 patients were included in the study resulting in a total of 1000 intracuff pressure readings. When compared to the neutral position, the intracuff pressure increased in 545 instances (68.1%) with changes in position of the head and neck. An increase in intracuff pressure was noted more frequently and to the greatest degree with head and neck flexion. The pressure decreased in 153 instances (19.1%), most frequently with neck extension. CONCLUSION: Significant changes in the intracuff pressure occur with changes in head and neck position. In several cases, this resulted in a significant increase in the intracuff pressure. For prolonged cases with the head and neck turned from the neutral position, the intracuff pressure should be measured following patient positioning to ensure that the intracuff pressure is within the clinically recommended range.

A review of the evaluation and management of velopharyngeal insufficiency in children.

This article highlights the most common causes of velopharyngeal insufficiency (VPI), and discusses routine evaluation and treatment algorithms for the management of VPI in children. VPI is a multifactorial condition that occurs commonly in syndromic and non-syndromic children. The most common features of VPI are audible hypernasal speech, facial grimacing, decreased speech intelligibility, nasal regurgitation, and nasal emission from failure to produce oronasal separation. Work-up of VPI typically involves radiologic and endoscopic testing performed with the assistance of a speech-language pathologist. Management of VPI involves initial speech therapy followed by operative repair with sphincter or pharyngeal flap pharyngoplasty, if needed.

The cost of screening for synchronous thyroid disease in patients presenting with primary hyperparathyroidism.

OBJECTIVE: To use decision analysis to compare the costs associated with minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE) in patients with primary hyperparathyroidism with regard to treatment of incidental synchronous thyroid disease. DESIGN: We developed a decision tree model to evaluate the cost of managing thyroid pathology in primary hyperparathyroidism with the following 3 approaches: MIP, MIP with preoperative ultrasonography, and routine BNE with intraoperative thyroid evaluation. We tested the robustness of the optimal decision with sensitivity analyses. SETTING: A tertiary care academic medical center. MAIN OUTCOME MEASURE: Total costs from a provider perspective. RESULTS: Minimally invasive parathyroidectomy without an active search for thyroid abnormalities was determined to have the lowest expected cost ($5275 per patient). Parathyroid surgery with routine preoperative thyroid ultrasonography and further thyroid treatment as indicated had an expected cost of $5910 per patient. Bilateral neck exploration with intraoperative thyroid evaluation and treatment of the thyroid gland had an expected cost of $5916 per patient. Sensitivity analyses confirmed the robustness of the results across a reasonable range of surgical and imaging costs. CONCLUSIONS: Minimally invasive parathyroidectomy is not contraindicated on the basis of cost by an inability to screen for synchronous thyroid disease. In addition, ultrasonographic screening of the thyroid glands of patients undergoing MIP is not cost prohibitive and, in fact, is less costly than BNE. Ultrasonography has the added advantage of confirming the location of the offending parathyroid.

The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model.

OBJECTIVE: To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). DESIGN: In vivo murine model, two arm controlled study. METHODS: Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 x 10(6) UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (> or =65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. RESULTS: Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). CONCLUSIONS: Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

The cost-effectiveness of additional preoperative ultrasonography or sestamibi-SPECT in patients with primary hyperparathyroidism and negative findings on sestamibi scans.

OBJECTIVE: To determine whether the use of additional preoperative imaging was cost-effective compared with bilateral neck exploration (BNE) for the treatment of primary hyperparathyroidism in patients with negative findings on scans with technetium Tc 99m sestamibi. DESIGN: We performed a cost-effectiveness analysis. The decision whether to proceed to BNE or obtain additional preoperative imaging using ultrasonography (US) or single-photon emission computed tomography with technetium Tc 99m sestamibi (SPECT) was modeled using decision analysis. We obtained probabilities of cure, detection of pathologic glands, and the correct side of the neck from recent literature. MAIN OUTCOME MEASURES: Expected cost, cure rate, and the incremental cost per cured case using the preoperative imaging strategies compared with BNE. RESULTS: The US strategy dominated the SPECT and BNE strategies, with a lower expected cost (USD $6030 vs USD $7131 and $8384, respectively) and a greater expected cure rate (99.42% vs 99.26% and 97.69%, respectively). Threshold analysis suggests that the preoperative imaging strategies continued to dominate unless the cost of BNE was less than USD $5400 or the cost of unilateral neck exploration exceeded USD $6500. The US strategy dominated SPECT as a preoperative imaging strategy if the cost of SPECT exceeded $12 or the cost of a US test was less than $1300. CONCLUSIONS: For the treatment of primary hyerparathyroidism in the patient with negative findings on technetium Tc 99m sestamibi scans, a strategy that uses additional preoperative US imaging appears to be cost-effective compared with SPECT or BNE.

Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue.

OBJECTIVE: To investigate the histopathological features of pathologic parathyroid specimens associated with negative preoperative technetium Tc 99m sestamibi scans. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: One hundred fourteen patients who underwent sestamibi scans before surgical exploration for primary hyperparathyroidism between 1996 and 2001. INTERVENTIONS: Surgical exploration and removal of parathyroid adenomas. MAIN OUTCOME MEASURES: Histopathological characteristics associated with true-positive and false-negative sestamibi scans, including parathyroid specimen weight, size, relative oxyphil and chief cell content, parathyroid hormone staining patterns, cellular architecture, and various immunohistochemical staining patterns. RESULTS: Twenty-three (24%) of 98 patients with parathyroid adenomas had negative sestamibi scan results. Among 20 age- and sex-matched patients with false-negative results vs 20 patients with true-positive results, tumor size (P = .04) and oxyphil cell content (P = .03) were found to be significantly different. CONCLUSION: Parathyroid gland size and oxyphil content are descriptive and predict differences between sestamibi properties of parathyroid adenomas but have no current therapeutic implications for parathyroid surgery.

A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003.

OBJECTIVE: To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism. STUDY DESIGN: A systematic literature review. RESULTS: Of the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc 99m -sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries. CONCLUSION: The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not "fool-proof" adjunct in parathyroid exploration surgery. SIGNIFICANCE: These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3.

Fusaric acid: a novel agent and mechanism to treat HNSCC.

OBJECTIVE: A new class of carboxylic acids has tumoricidal activity for head and neck squamous cell cancer (HNSCC). Fusaric acid (FA) can chelate divalent cations, especially zinc, and inactivate zinc finger proteins involved in DNA repair and protein synthesis. METHODS: 2 squamous carcinoma lines were utilized for in vitro and in vivo portions of this study. Cell counting and flow cytometry were used to analyze cells in culture in treatment and control groups over 96 hours. HNSCC subcutaneous implants were created in treatment and control groups of BALB-c nude mice (N = 30). RESULTS: In vitro studies demonstrated significant changes in cell numbers and cell cycle. In vivo studies of daily intralesional therapy for 1 month also showed reduced onset of growth and overall growth compared to controls. CONCLUSION: FA appears to have a tumoristatic/tumoricidal effect on HNSCC. Further nude mice studies are needed to optimize dosing and administration regimens for FA in anticipation of clinical trials.