Faculty Bibliography

Cancer patients often suffer from pain and most will be prescribed mu-opioids. mu-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that mu and delta opioid receptors are separately expressed on IB4 (-) and IB4 (+) neurons, which control thermal and mechanical pain, respectively. In this study we investigated IB4 (+) and IB4 (-) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a delta opioid receptor agonist and a P2X(3) antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective delta-opioid receptor agonist or P2X(3) antagonist, might be useful in treating oral cancer pain. PERSPECTIVE: To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and IB4 (-) neurons. Characterization of these 2 subsets of putative nociceptors is important for further development of effective clinical cancer pain relief.

Object Staged resection of large vestibular schwannomas (VSs) has been proposed as a strategy to improve facial nerve outcomes and morbidity. The authors report their experience with 2-stage resections of large VSs and analyze the indications, facial nerve outcomes, surgical results, and complications. The authors compare these results with those of a similar cohort of patients who underwent a single-stage resection. Methods A retrospective review of all patients (age > 18 years) who underwent surgery from 2002 to 2010 for large (>/= 3 cm) VSs at the authors' institution with a minimum of 6 months follow-up was undertaken. A first-stage retrosigmoid approach (without meatal drilling) was performed to remove the cerebellopontine angle portion of the tumor and to decompress the brainstem. A decision to stage the operation was made intraoperatively if there was cerebellar or brainstem edema, excessive tumor adherence to the facial nerve or brainstem, a poorly stimulating facial nerve, or a thinned or splayed facial nerve. A second-stage translabyrinthine approach was performed at a later date to remove the remaining tumor. The single-stage resection consisted of a retrosigmoid approach with meatal drilling. Patient charts were evaluated for tumor size, extent of resection, tumor recurrence, House-Brackmann facial nerve function grade, and complications. Results Twenty-eight and 19 patients underwent 2- or single-stage resection of a large VS, respectively. The average tumor size was 3.9 cm (range 3.2-7 cm) in the 2-stage group and 3.9 cm (range 3.1-5 cm) in the single-stage group. The mean follow-up was 36 +/- 19 months in the 2-stage group versus 24 +/- 14 months in the single-stage group. Gross-total or near-total resection was achieved in 27 (96.4%) of 28 patients in the 2-stage group and 15 (79%) of 19 patients in the single-stage group (p < 0.01). Anatomical facial nerve preservation was achieved in all but 1 patient (94.7%), and there were no recurrences on follow-up imaging in the 2-stage group. Good facial nerve functional outcome (House-Brackmann Grades I and II) at last follow-up was achieved in 23 (82%) of 28 patients in the 2-stage group and 10 (53%) of 19 patients in the single-stage group (p < 0.01). Cerebrospinal fluid leak-related complications (intracranial hypotension, blood patch, and lumboperitoneal shunt for pseudomeningocele) were more common in the 2-stage group. There were no postoperative strokes, hemorrhages, or deaths in either group. Conclusions The authors' results suggest that staged resection of large VSs may potentially achieve better facial nerve outcomes. There does not appear to be added neurological morbidity with staged resections.

Today most cochlear implant users achieve above 80% on standard speech recognition in quiet testing, and enjoy excellent device reliability. Despite such success, conventional designs often fail to provide the frequency resolution required for complex listening tasks. Furthermore, performance variability remains a vexing problem, with a select group of patients performing poorly despite using the most recent technologies and processing strategies. This article provides a brief history of the development of cochlear implant technologies, reviews current implant systems from all 3 major manufacturers, examines recently devised strategies aimed at improving device performance, and discusses potential future developments.

Although functional status serves as a major predictor of morbidity, researchers and clinicians use different terms and measures, limiting comparisons across studies. To demonstrate how differing measures may generate varied findings, we compared and contrasted data from the SF-12 Health Survey Physical Component Summary Scale (SF-12 PCS) and the Enforced Social Dependency Scale (ESDS). The sample consisted of 49 women aged 65 and older recovering from gynecological cancer surgery with data collection at baseline (postoperative period) and then at 3 and 6 months. Analysis of the relationship between SF-12 PCS and ESDS over time using generalized estimating equations (GEE) demonstrated the relationship was less than 1.0, signaling less than perfect agreement between measures (beta = 0.16, P = .002). These findings suggest that that the 2 measures are not interchangeable and may produce conflicting evidence. This highlights the importance of researchers' and clinicians' careful conceptualization and operationalization of functional status before measure selection.

The purposes of this study were to determine the occurrence rate for preoperative breast pain; describe the characteristics of this pain; evaluate for differences in demographic and clinical characteristics; and evaluate for variations in pro- and anti-inflammatory cytokine genes between women who did and did not report pain. Patients (n = 398) were recruited prior to surgery and completed self-report questionnaires on a number of pain characteristics. Genotyping was done using a custom genotyping array. Women (28.2%) who reported breast pain were significantly younger (P < .001); more likely to be nonwhite (P = .032); reported significantly lower Karnofsky Performance Status scores (P = .008); were less likely to be postmenopausal (P = .012); and had undergone significantly more biopsies (P = .006). Carriers of the minor allele for a single nucleotide polymorphism in interleukin (IL)1-receptor 1 (IL1R1) (rs2110726) were less likely to report breast pain prior to surgery (P = .007). Carriers of the minor allele for a single nucleotide polymorphism in IL13 (rs1295686) were more likely to report breast pain prior to surgery (P = .019). Findings suggest that breast pain occurs in over a quarter of women who are about to undergo breast cancer surgery. Based on phenotypic and genotypic characteristics found, inflammatory mechanisms contribute to preoperative breast pain. PERSPECTIVE: In women with breast cancer, preoperative pain may be associated with increases in inflammatory responses associated with an increased number of biopsies. In addition, differences in cytokine genes may contribute to this preoperative breast pain.

The oral mucosa's accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

PURPOSE: To determine the feasibility of using a virtual auditory test material to evaluate reverberation and noise effects on speech recognition of pediatric cochlear implant (CI) users and to compare their performance with that of children with normal hearing. METHOD: Virtual test materials representing nonreverberant and reverberant environments were used to measure speech recognition of 7 children with CIs in quiet and in noise, and of 18 children with normal hearing in the quiet condition. Performance of CI users in noise (signal-to-noise ratio resulting in 50% performance) was compared to normative data from a previous study (Neuman, Wroblewski, Hajicek, & Rubinstein, 2010). For CI users, stimuli were sent directly to the CI speech processor via auxiliary input, whereas children with normal hearing were tested using insert phones. RESULTS: The speech recognition of children with CIs decreased significantly in the reverberant condition. There were individual differences in susceptibility to reverberation. Children with CIs also required higher signal-to-noise ratios than children with normal hearing in the reverberant condition. CONCLUSION: Direct connect testing with reverberant test materials allows assessment of speech recognition under conditions typical of classrooms and could be useful in identifying children with CIs whose performance decreases significantly in the presence of reverberation and noise.

Hierarchical models of auditory processing often posit that optimal stimuli, i.e., those eliciting a maximal neural response, will increase in bandwidth and decrease in modulation rate as one ascends the auditory neuraxis. Here, we tested how bandwidth and modulation rate interact at several loci along the human central auditory pathway using functional MRI in a cardiac-gated, sparse acquisition design. Participants listened passively to both narrowband (NB) and broadband (BB) carriers (1/4- or 4-octave pink noise), which were jittered about a mean sinusoidal amplitude modulation rate of 0, 3, 29, or 57 Hz. The jittering was introduced to minimize stimulus-specific adaptation. The results revealed a clear difference between spectral bandwidth and temporal modulation rate: sensitivity to bandwidth (BB > NB) decreased from subcortical structures to nonprimary auditory cortex, whereas sensitivity to slow modulation rates was largest in nonprimary auditory cortex and largely absent in subcortical structures. Furthermore, there was no parametric interaction between bandwidth and modulation rate. These results challenge simple hierarchical models, in that BB stimuli evoked stronger responses in primary auditory cortex (and subcortical structures) rather than nonprimary cortex. Furthermore, the strong preference for slow modulation rates in nonprimary cortex demonstrates the compelling global sensitivity of auditory cortex to modulation rates that are dominant in the principal signals that we process, e.g., speech.

Acoustic neuromas (ANs) are the most common tumors of the cerebellopontine angle. Although numerous advances have occurred in the operative management of AN and perioperative care leading to a significant decrease in associated morbidity and mortality, there are several characteristic complications that accompany microsurgical resection of AN. Understanding the types and rates of complications in association with the various approaches is essential in patient counseling, establishing patient expectations, and ensuring the best patient outcome. In this article, the justification for incomplete surgical resection is discussed. Also, the most common complications of AN microsurgery and the associated management are reviewed.