Faculty Bibliography

OBJECTIVE: To further define the spectrum of clinical presentation and explore the histologic sequelae of jugular bulb abnormalities (JBAs). DESIGN: Retrospective review. SETTING: Academic medical center. PATIENTS: Thirty patients with radiologic evidence of inner ear dehiscence by JBA. MAIN OUTCOME MEASURE: Thirty patients with radiologic inner ear dehiscence by JBA and 1579 temporal bone specimens were evaluated for consequences from JBA. RESULTS: We found that JBA-associated inner ear dehiscence could be identified on computed tomography of the temporal bone but not on magnetic resonance imaging scan. Jugular bulb abnormalities eroded the vestibular aqueduct most often (in 25 patients), followed by the facial nerve (5 patients) and the posterior semicircular canal (4 patients). Half of the patients (15) were asymptomatic. Results from vestibular evoked myogenic potential (VEMP) tests were positive in 8 of 12 patients with inner ear dehiscence. Histologically, only 2 of 41 temporal bones with dehiscence of the vestibular aqueduct demonstrated endolymphatic hydrops. CONCLUSIONS: Jugular bulb abnormalities can erode into the vestibular aqueduct, facial nerve, and the posterior semicircular canal. While symptoms may include pulsatile tinnitus, vertigo, or conductive hearing loss, in contrast to earlier reports, half of the patients were asymptomatic. Dehiscence of vestibular aqueduct rarely leads to clinical or histologic hydrops. The VEMP testing was useful in confirming the presence of inner ear dehiscence due to JBAs. Because the natural history of JBAs is unknown, these patients should be followed closely to evaluate for progression of the JBA or development of symptoms

Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome characterized by bilateral vestibular schwannomas (VS) which often result in deafness despite aggressive management. Meningiomas, ependymomas, and other cranial nerve and peripheral schwannomas are also commonly found in NF2 and collectively lead to major neurologic morbidity and mortality. Traditionally, the overall survival rate in patients with NF2 is estimated to be 38% at 20 years from diagnosis. Hence, there is a desperate need for new, effective therapies. Recent progress in understanding the molecular basis of NF2 related tumors has aided in the identification of potential therapeutic targets and emerging clinical therapies. In June 2010, representatives of the international NF2 research and clinical community convened under the leadership of Drs. D. Gareth Evans (University of Manchester) and Marco Giovannini (House Research Institute) to review the state of NF2 treatment and clinical trials. This manuscript summarizes the expert opinions about current treatments for NF2 associated tumors and recommendations for advancing therapies emerging from that meeting. The development of effective therapies for NF2 associated tumors has the potential for significant clinical advancement not only for patients with NF2 but for thousands of neuro-oncology patients afflicted with these tumors.

Context: While clinical successes and descriptions have been reported in a few texts, no data exist to define the utility of flow phonation to improve voice quality in patients with laryngeal hyperfunction. Aims: To provide pilot data regarding the utility of three exercises (gargling, cup bubble blowing, and stretch-and-flow) to improve phonatory airflow during voicing in patients with laryngeal hyperfunction. Settings and Design: Outpatient Voice and Swallowing Center in a University Medical Center. Materials and Methods: Participants received five treatment sessions and were evaluated prior to treatment and after each session using a Phonatory Aerodynamic System to measure airflow during voicing tasks. Noise-to-harmonic ratio and perceptual voice measures were also obtained, as was self-perception of voice handicap. Statistical Analysis Used: Repeated All increased airflow and decreased laryngeal airway resistance over five sessions. Measures Analysis of Variance. Results: Six participants completed the protocol. All participants decreased self-perception of voice handicap and improved on noise-to-harmonic ratio and perceptual ratings of vocal quality. Conclusions: Data derived on a small sample of patients in an exploratory investigation suggest further research into the use of these three exercises to improve airflow with voicing and improve vocal quality in patients with laryngeal hyperfunction is warranted

PURPOSE/OBJECTIVE:Perineural invasion (PNI) by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT) may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control PNI remain undefined. EXPERIMENTAL DESIGN/METHODS:An in vitro co-culture system of dorsal root ganglia (DRG) and pancreatic cancer cells was used as a model of PNI. An in vivo murine sciatic nerve model was used to study how RT to nerve or cancer affects nerve invasion by cancer. RESULTS:Cancer cell invasion of the DRG was partially dependent on DRG secretion of glial-derived neurotrophic factor (GDNF). A single 4 Gy dose of radiation to the DRG alone, cultured with non-radiated cancer cells, significantly inhibited PNI and was associated with decreased GDNF secretion but intact DRG viability. Radiation of cancer cells alone, co-cultured with non-radiated nerves, inhibited PNI through predominantly compromised cancer cell viability. In a murine model of PNI, a single 8 Gy dose of radiation to the sciatic nerve prior to implantation of non-radiated cancer cells resulted in decreased GDNF expression, decreased PNI by imaging and histology, and preservation of sciatic nerve motor function. CONCLUSIONS:Radiation may impair PNI through not only direct effects on cancer cell viability, but also an independent interruption of paracrine mechanisms underlying PNI. RT modulation of the nerve microenvironment may decrease PNI, and hold significant therapeutic implications for RT dosing and field design for patients with cancers exhibiting PNI.

Background. LCH is a benign vascular growth of the skin and mucous membranes commonly affecting the head and neck. Since it was first described in the nineteenth century, this entity has been variously known as "human botryomycosis" and "pyogenic granuloma." The shifting nomenclature reflects an evolving understanding of the underlying pathogenesis. We review the histopathology of and current epidemiological data pertaining to LCH which suggests that the development of these lesions may involve a hyperactive inflammatory response influenced by endocrine factors. We report two new cases of pediatric lobular capillary hemangioma (LCH) of the nasal cavity and review current theories regarding the etiology, diagnosis, and treatment of nasal LCH. Methods. Retrospective case series. Case Series. Two adolescent females presented with symptoms of recurrent epistaxis, nasal obstruction, and epiphora. Both patients underwent computed tomography imaging and biopsy of their intranasal mass. The tumors were excised using image-guided transnasal endoscopic technique. Seven other cases of nasal LCH have been reported to date in the pediatric population. Conclusion. Nasal LCH is a rare cause of an intranasal mass and is associated with unilateral epistaxis, nasal obstruction, and epiphora. We advocate for image-guided endoscopic excision of LCH in the adolescent population.

Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva.

OBJECTIVES/OBJECTIVE:To compare hearing outcomes in patients with far advanced otosclerosis (FAO) undergoing cochlear implantation to an age-matched group of controls, to describe the effects of cochlear ossification on hearing, and to review the adverse effects of implantation in patients with FAO. HYPOTHESIS/OBJECTIVE:Hearing performance in patients with FAO after cochlear implantation is comparable to similarly treated postlingually deafened adults without FAO. Ossification or retrofenestral otosclerosis does not predict poor hearing outcomes. Modiolar-hugging technology reduces postoperative facial nerve stimulation. STUDY DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Academic neurotologic tertiary referral center. PATIENTS/METHODS:Thirty patients with FAO, who metaudiological criteria for cochlear implantation, were compared to 30 age-matched controls, postlingually deafened by non-otosclerotic causes. MAIN OUTCOME MEASURES/METHODS:Audiometric pre- and postoperative speech reception threshold, word, and sentence scores were analyzed. The presence of retrofenestral findings on computed tomography or intraoperative cochlear ossification were noted. RESULTS:In the FAO group, radiographic abnormalities were noted in 26.4% of patients. Intraoperative ossification requiring drillout was seen in 29.4% of patients. None developed postoperative facial nerve stimulation. There was no difference between the FAO and control groups in the mean short-term and long-term postoperative speech reception threshold, word, and sentence scores (P = .77). The presence of radiographic abnormalities did not predict hearing outcome. Intraoperative cochlear ossification was not associated with worse short-term word and sentence scores (P = .58 and 0.79, respectively), and for the long-term hearing outcome (P = .24). CONCLUSIONS:In patients with FAO, effective and safe hearing rehabilitation can be accomplished with cochlear implantation.