Faculty Bibliography

OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the prevalence of vocal pathology among first-year acting students. STUDY DESIGN: A retrospective review of 30 first-year graduate-level drama students between 2009 and 2011 was performed. METHODS: Stroboscopy, Voice Handicap Index-10 questionnaires, and acoustic measures were analyzed. RESULTS: The prevalence of incomplete glottal closure, laryngeal hyperfunction, and decreased mucosal wave was 62%, 59%, and 55%, respectively. Laryngoscopic findings consistent with laryngopharyngeal reflux (LPR) were demonstrated in 48% of subjects. Subgroup analysis of laryngeal hyperfunctioning (HF) and nonhyperfunctioning drama students revealed an increased prevalence of all videostroboscopic abnormalities in the HF group. The increased prevalence of LPR stigmata in HF actors reached statistical significance (P = 0.04). CONCLUSIONS: The vocal demands of actors are unique, requiring the effective use of volume, pitch control, and endurance. This is the first study that systematically analyzes the prevalence of vocal pathology in actors. This study will continue throughout their education, anticipating that our feedback along with their vocal training will improve outcomes.

BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns. METHODS: We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and established molecular subgroups using a nanoString-based assay on formalin-fixed paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival after recurrence were assessed in a subgroup-specific manner. Two independent, non-overlapping cohorts (cohort 2: samples from patients with recurrent medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012; cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were analysed to confirm and validate observations. When possible, molecular subgrouping was done on tissue obtained from both the initial surgery and at recurrence. RESULTS: Cohort 1 consisted of 30 patients with recurrent medulloblastomas; nine with local recurrences, and 21 with metastatic recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs (five pairs from cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This finding was validated in 17 pairs from cohort 3. When analysed in a subgroup-specific manner, local recurrences in cohort 1 were more frequent in SHH tumours (eight of nine [89%]) and metastatic recurrences were more common in group 3 and group 4 tumours (17 of 20 [85%] with one WNT, p=0.0014, local vs metastatic recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of recurrence was confirmed in cohort 2 (p=0.0013 for local vs metastatic recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0.0001). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival after recurrence was significantly longer in patients with group 4 tumours in cohort 1 (p=0.013) than with other subgroups, which was confirmed in cohort 2 (p=0.0075), but not cohort 3 (p=0.70). INTERPRETATION: Medulloblastoma does not change subgroup at the time of recurrence, reinforcing the stability of the four main medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours. Refinement of therapy for patients with group 3 or group 4 tumours should focus on metastases. FUNDING: Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children and The University of Toronto.

OBJECTIVES: To determine which demographic or performance variables are associated with inconsistent use of a second implant in pediatric recipients of sequential bilateral cochlear implants (CIs). METHODS: A retrospective chart review was conducted on pediatric recipients of sequential bilateral CIs. Children were divided into two age groups, 5-9 and 10-17 years of age. For each group, we examined whether inconsistent use of the second implant (CI-2) was associated with a variety of demographic variables, or speech-perception scores. RESULTS: In children aged 5-9 years, inconsistent use of CI-2 was not significantly associated with any demographic variable, but was related to both the word-recognition score with CI-2, and the difference in word-recognition scores between the first implant (CI-1) and CI-2. In children aged 10-17 years, these relationships were not significant due to smaller number of subjects. Finally, CI-2 word-recognition scores across all children were significantly correlated with the age of implantation for both CI-1 and CI-2, and the time between CI-1 and CI-2 surgeries. DISCUSSION: Speech-recognition scores obtained with CI-2, and the extent to which it differs from CI-1, are most closely related with inconsistent use of CI-2 in pediatric sequential implantees. These results are consistent with similar data previously reported by other investigators. While children implanted with CI-2 at a later age generally perform more poorly, most children still use both implants, and benefit from CI-2 even when receiving the implant as an adolescent. CONCLUSION: In pediatric recipients of sequential bilateral CIs, inconsistent use of CI-2 is related to the speech recognition scores with CI-2, and the difference in speech-recognition scores between CI-1 and CI-2. In addition, speech-recognition scores with CI-2 are related to the amount of time between CI-1 and CI-2 surgeries, and the age of implantation for both CI-1 and CI-2.

BACKGROUND: A variety of tumors arise in or extend to the infratemporal fossa. We investigated the outcome of surgical management of these tumors. METHODS: We conducted a retrospective review of a craniofacial approach to resection of infratemporal fossa tumors from 1992 to 2008 in a cancer center. RESULTS: Forty-three patients underwent resection of a infratemporal fossa tumors (68% men). Median age was 46 years (range, 1-81 years). The most common pathology was sarcoma (13; 30%). Twenty-two tumors (51%) were recurrent. Twenty patients (46%) underwent resection of tumors from the infratemporal fossa, 5 (12%) required resection of the anterior skull base, and 18 (42%) required orbital exenteration, additionally. Thirty-one patients (72%) required reconstruction with free tissue transfer. Twenty-seven patients (62.8%) required further treatment with radiation and/or chemotherapy. Complications occurred in 9 patients (21%). Six patients (14%) underwent salvage operations. Median follow-up was 24 months. Median overall survival and 3-year survival were 40 months and 59.6%. CONCLUSION: Tumors involving the infratemporal fossa can be resected with acceptable morbidity and long-term survival.

BACKGROUND:Current immunosuppressive therapy after heart transplantation either generally suppresses the recipient's entire immune system or is mainly targeting T-lymphocytes. Monocytes/macrophages are recognized as a hallmark of acute allograft rejection, but the roles that they play are not well characterized in vivo, because the tools for accessing in situ macrophage infiltration are lacking. In this study, we used MRI to investigate the role of macrophages in acute heart allograft rejection by cellular and functional MRI with selectively depleted systemic macrophages without affecting other leukocyte population, as well as to explore the possibility that macrophages could be an alternative therapeutic target. METHODS AND RESULTS/RESULTS:A rodent heterotopic working heart-lung transplantation model was used for studying acute allograft rejection. Systemic macrophages were selectively depleted by treating recipient animals with clodronate-liposomes. Macrophage infiltration in the graft hearts was monitored by cellular MRI with in vivo ultrasmall superparamagnetic iron oxide particles labeling. Graft heart function was evaluated by tagging MRI followed by strain analysis. Clodronate-liposome treatment depletes circulating monocytes/macrophages in transplant recipients, and both cellular MRI and pathological examinations indicate a significant reduction in macrophage accumulation in the rejecting allograft hearts. In clodronate-liposome-treated group, allograft hearts exhibited preserved tissue integrity, partially reversed functional deterioration, and prolonged graft survival, compared with untreated controls. CONCLUSIONS:Cardiac cellular and functional MRI is a powerful tool to explore the roles of targeted immune cells in vivo. Our results indicate that macrophages are essential in acute cardiac allograft rejection, and selective depletion of macrophages with clodronate-liposomes protects hearts against allograft rejection, suggesting a potential therapeutic avenue. Our findings show that there is a finite risk of forming an intraventricular mass, presumably from the cellular debris or lipid material. Further optimization of the dosing protocol is necessary before clinical applications.

IMPORTANCE/OBJECTIVE:At many institutions, computed tomography with iodinated intravenous contrast medium is the preferred imaging modality for staging of the neck in squamous cell carcinoma of the head and neck. However, few studies have specifically assessed the diagnostic accuracy of computed tomography for determining the presence or absence of extracapsular spread (ECS). OBJECTIVE:To determine the accuracy of modern, contrast-enhanced, multidetector computed tomography in the diagnosis of ECS of cervical lymph node metastases from squamous cell carcinoma of the head and neck. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Retrospective observational study at an academic tertiary referral center among 100 consecutive patients between May 1, 2007, and February 1, 2012, who underwent a lateral cervical neck dissection for squamous cell carcinoma of the head and neck with neck metastases of at least 1 cm in diameter on pathologic assessment. Exclusion criteria included malignant neoplasms other than squamous cell carcinoma, a delay in surgery longer than 6 weeks from the time of staging computed tomography, and prior treatment of the neck or recurrent disease or a second primary. MAIN OUTCOMES AND MEASURES/METHODS:Each patient was independently assigned a subjective score for the presence of ECS by 2 Certificate of Added Qualification-certified neuroradiologists according to a 5-point scale. Receiver operating characteristic curves were generated, and sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for each observer. RESULTS:The areas under the receiver operating characteristic curve for observers 1 and 2 are 0.678 (95% CI, 0.578-0.768) and 0.621 (95% CI, 0.518-0.716), respectively. For observer 1, the positive and negative predictive values for the detection of ECS were 84% (95% CI, 68%-93%) and 49% (95% CI, 36%-62%), respectively. For observer 2, the positive and negative predictive values for the detection of ECS were 71% (95% CI, 57%-82%) and 48% (95% CI, 32%-64%), respectively. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Computed tomography cannot be used to reliably determine the presence of pathologic ECS. Radiologic findings suggestive of ECS should not be relied on for treatment planning in squamous cell carcinoma of the head and neck.

AIM: To evaluate the relationship between intraoperative blood loss and juvenile nasopharyngeal angiofibroma (JNA) vascular supply and tumour stage in patients who underwent superselective external carotid artery (ECA) embolization. This series is unique in that all embolizations were performed by dedicated paediatric interventional radiologists at a tertiary referral paediatric centre. MATERIALS AND METHODS: Seventeen male patients treated from January 2002 to August 2009 underwent preoperative angiography and embolization using polyvinyl alcohol (PVA) particles. Tumours were graded using three different staging systems based on preoperative imaging and correlated to surgical blood loss. All patients underwent bilateral internal and external carotid angiography, with embolization of ECA tumour supply via microcatheter delivery of PVA particles. Particle size ranged from 150-500 mum with a mean size of 250-355 mum. Surgical resection was performed with either endoscopic or open techniques within 24 h and intraoperative blood loss was reported. RESULTS: Seven lesions were supplied strictly by the ECA circulation and had mean surgical blood loss of 336 ml. Twelve lesions had both ECA and internal carotid artery (ICA) supply and had mean surgical blood loss of 842 ml. The difference in blood loss in these two groups was statistically significant (p = 0.03). There was no case of inadvertent intracranial or ophthalmic embolization. There were statistically significant correlations between estimated surgical blood loss and the Andrews (p = 0.008), Radkowski (p = 0.015), and University of Pittsburgh Medical Center (UPMC; p = 0.015) preoperative tumour staging systems, respectively. CONCLUSION: Preoperative embolization of JNA tumours can be safely performed without neurological complications. The present study identified a statistically significant difference in intraoperative blood loss between those lesions with a purely ECA vascular supply and a combination of ECA and ICA vascular supply. Angiography is helpful in delineating ICA supply and can help guide surgical planning.

OBJECTIVE: To compare the effectiveness of two types of treatment for unilateral hearing loss (UHL), bone-anchored hearing instruments (BAHI) and a dental device (SoundBite). DESIGN: Either BAHI or SoundBite were worn for 30 days, and then the devices were swapped and the second device was worn for 30 days. Measures included unaided and aided sound-field thresholds, sound localization, and perception of speech in babble. The APHAB questionnaire was administered for each trial period. STUDY SAMPLE: Nine adult BAHI wearers with UHL. RESULTS: Mid-frequency aided thresholds were lower for SoundBite than for BAHI. Both devices gave benefits for localization after 30 days, but there was no difference between devices. Speech perception was better for both devices than for unaided listening when the target speech came from the poorer hearing side or in front, and the interfering babble came from the better-hearing side. There was no consistent difference between devices. APHAB scores were better for SoundBite than for BAHI. CONCLUSIONS: Speech perception and sound localization were similar for the two types of device, but the SoundBite led to lower aided thresholds and better APHAB scores than the BAHI.