Faculty Bibliography

OBJECTIVES: A preponderance of literature supports the safety of office-based flexible endoscopic procedures of the upper aerodigestive tract; however, until recently there were no data regarding hemodynamic stability during these procedures. A recent study showed intraprocedure changes in patients' hemodynamic parameters, raising the concern that perhaps patients should be monitored during these procedures. The aim of our study was to determine whether physiologically significant alterations in vital signs occur during office-based flexible endoscopic procedures. METHODS: We performed a retrospective review of 100 consecutive patients who underwent office-based flexible endoscopic procedures of the upper aerodigestive tract from July 2010 to October 2011. Baseline values and the maximal changes in systolic blood pressure, diastolic blood pressure, heart rate, and oxygen saturation were recorded and compared. RESULTS: One hundred consecutive patients were included in the study. Twenty-one patients (21%) had severe hypertension and 40 patients (40%) had tachycardia during the procedure. The mean change overall in systolic blood pressure was 26.2 mm Hg (p < 0.001), the mean change in diastolic blood pressure was 13.9 mm Hg (p < 0.001), the mean change in heart rate was 16.6 beats per minute (p < 0.001), and the mean change in oxygen saturation was 1.6% (p < 0.001). These changes were significant. On further breakdown into groups, patients over 50 years of age and patients who were undergoing esophageal or laser procedures had significant elevations in heart rate (p = 0.01 and p = 0.04, respectively). An elevation in diastolic blood pressure was also significant in patients who were undergoing esophageal or laser procedures (p = 0.04 for both). CONCLUSIONS: These data concur with those of the previous report that found potentially significant hemodynamic changes during office-based procedures. Although preliminary, our findings suggest that it may be wise to monitor vital signs in patients over 50 years of age and patients who are undergoing an esophageal or laser procedure who are at risk for complications that could arise from tachycardia and hypertension.

OBJECTIVE: Laryngomalacia is best known as a self-resolving infantile disorder characterized by inspiratory stridor with occlusion of the larynx by collapse of arytenoid tissues due to Bernoulli forces. Adult laryngomalacia has been sporadically described in the literature. We identified a series of patients with aerodynamic supraglottic collapse mimicking laryngomalacia in our Otolaryngology clinic. STUDY DESIGN: Case series. METHODS/PATIENTS: A series of five patients from our Otolaryngology clinic with aerodynamic supraglottic collapse presented with complaints ranging from noisy breathing to dyspnea with exertion. Diagnosis was made using rest and exercise flexible laryngoscopy. RESULTS: Symptoms resolved in all patients who underwent traditional or modified supraglottoplasty. CONCLUSIONS: These patients, all with abnormal corniculate/cuneiform motion occluding the airway during forceful inspiration, reinforce the diagnostic role of rest and exercise flexible laryngoscopy in patients with dyspnea and stridor. These results may suggest that aerodynamic supraglottic collapse is an underdiagnosed clinical entity.

Objective : To demonstrate the feasibility of simultaneous-acquired magnetic resonance imaging (MRI) and high-quality synchronized audio recording for evaluating velopharyngeal closure. Design : Institutional Review Board-approved case series. Setting : Tertiary care hospital. Patients : Three healthy adult volunteers with a normal speech pattern. Interventions : MRI with simultaneous recorded audio files evaluating velopharyngeal closure. Main outcome measure : Precise imaging and audio coordination of specific phonatory tasks. Results : Synchronization of MRI and audio in all three adults. Conclusion : Our novel imaging and audio protocol provides simultaneous acquired MRI with synchronized high quality audio for evaluating velopharyngeal closure. This technique may provide the opportunity to improve diagnosis and surgical planning in patients with velopharyngeal insufficiency.

Interferon (IFN-α) is effective therapy for polycythemia vera (PV) patients, but it is frequently interrupted because of adverse events. To permit the long-term use of IFN, we propose combining low doses of IFN with Nutlin-3, an antagonist of MDM2, which is also capable of promoting PV CD34(+) cell apoptosis. Combination treatment with subtherapeutic doses of Peg IFN-α 2a and Nutlin-3 inhibited PV CD34(+) cell proliferation by 50% while inhibiting normal CD34(+) cells by 30%. Combination treatment with Nutlin-3 and Peg IFN-α 2a inhibited PV colony formation by 55%-90% while inhibiting normal colony formation by 22%-30%. The combination of these agents also decreased the proportion of JAK2V617F-positive hematopoietic progenitor cells in 6 PV patients studied. Treatment with low doses of Peg IFN-α 2a combined with Nutlin-3 increased phospho-p53 and p21 protein levels in PV CD34(+) cells and increased the degree of apoptosis. These 2 reagents affect the tumor suppressor p53 through different pathways with Peg IFN-α 2a activating p38 MAP kinase and STAT1, leading to increased p53 transcription, whereas Nutlin-3 prevents the degradation of p53. These data suggest that treatment with low doses of both Nutlin-3 combined with Peg IFN-α 2a can target PV hematopoietic progenitor cells, eliminating the numbers of malignant hematopoietic progenitor cells.

Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2-serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.

OBJECTIVE: The objective of this study was to review our pediatric emergency department's (ED's) utilization of computed tomography (CT) in the diagnosis of peritonsillar abscess (PTA) and treatment outcomes. METHODS: This study used case series with chart review. RESULTS: From January 2007 to January 2009, 148 patients were seen in our ED for possible PTA. Mean age at presentation was 11.8 years (range, 10 months to 18 years); 81 (54.7%) of 148 were females. Computed tomography was ordered in 96 (64.9%) of 148 patients, of which 73 (49.3%) 148 were confirmed to have PTA. Mean age of patients who underwent CT was younger when compared with those who did not have CT performed (mean, 11 vs 13 years; P = 0.02). Unilateral PTA was found in 65 (43.9%) of 148, bilateral in 8 (5.4%) of 148, and intratonsillar in 25 patients (16.9%). Concomitant CT findings of parapharyngeal space involvement were found in 19 (12.8%), and retropharyngeal space involvement in 11 (7.4%). Admission was necessary for 104 (71.2%) of 148 patients, whereas 42 were discharged from the ED. Transoral needle aspiration and/or incision and drainage were performed in the ED in 41 patients, with purulence identified in 33 (80.5%) of 41. Rapid strep testing was positive in 40 (32%) of 124 patients tested. Operative treatment was necessary in 44 patients (29.7%), 34 underwent incision and drainage, and 10 underwent quinsy tonsillectomy. CONCLUSIONS: Computed tomography is commonly utilized in the ED for the evaluation of PTA and is ordered more often in younger children.

Posterior tongue defects present a unique reconstructive challenge. The various reconstructive options available for treating the defect created by a posterior hemiglossectomy frequently result in a distorted tongue and functional impairment. This paper describes a novel sliding anterior hemitongue flap to allow reconstruction of moderate resection defects (i.e. for T1-T2 tongue squamous cell carcinomas) of the posterior tongue. By mobilizing the anterior tongue, near normal mobility and tongue length are maintained. This surgical technique may be performed alone intraorally or in combination with a neck dissection.

PURPOSE: This dedicated QTc study was designed to evaluate the effect of the mammalian target of rapamycin inhibitor, ridaforolimus, on the QTc interval in patients with advanced malignancies. METHODS: We conducted a fixed-sequence, single-blind, placebo-controlled study. Patients (n = 23) received placebo on day 1 and a single 100-mg oral dose of ridaforolimus on day 2 in the fasted state. Holter electrocardiogram (ECG) monitoring was performed for 24 h after each treatment, and blood ridaforolimus concentrations were measured for 24 h after dosing. The ECGs were interpreted in a blinded fashion, and the QT interval was corrected using Fridericia's formula (QTcF). After a washout of at least 5 days, 22 patients went on to receive a therapeutic regimen of ridaforolimus (40 mg orally once daily for 5 days per week). RESULTS: The upper limit of the two-sided 90 % confidence interval for the placebo-adjusted mean change from baseline in QTcF was <10 ms at each time point. No patient had a QTcF change from baseline >30 ms or QTcF interval >480 ms. Geometric mean exposure to ridaforolimus after the single 100-mg dose was comparable to previous experience with the therapeutic regimen. There appeared to be no clear relationship between individual QTcF change from baseline and ridaforolimus blood concentrations. Ridaforolimus was generally well tolerated, with adverse events consistent with prior studies. CONCLUSIONS: Administration of the single 100-mg dose of ridaforolimus did not cause a clinically meaningful prolongation of QTcF, suggesting that patients treated with ridaforolimus have a low likelihood of delayed ventricular repolarization.