Faculty Bibliography

Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction. PERSPECTIVE: Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

Brachytherapy consists of placing radioactive sources within, or directly adjacent to a tumor, and is a means of delivering highly targeted and conformal radiation. While its history dates back to the origins of the field, in recent years brachytherapy treatment paradigms have been evolving considerably. This has been driven primarily by advancements in imaging, which allow for precise placement of sources and applicators under image guidance, and volume-based optimization to ensure adequate tumor coverage while sparing adjacent normal tissue. There has been a shift towards high-dose-rate (HDR) brachytherapy for many of the disease sites treated with brachytherapy. Simultaneously, with increasingly conformal treatment, there has been a shift towards utilization of higher doses per fraction, over fewer fractions, for specific disease sites where hypofractionation is believed to confer a radiobiological benefit. Here we review recent data and trends for those disease sites and conditions that are commonly treated with brachytherapy, including prostate, gynecologic, breast, head and neck, and skin cancers and salvage of recurrent disease.

OBJECTIVE: The preferential delayed enhancement of the perilymphatic space enables detection of the non-enhancing endolymphatic hydrops present in patients with Meniere's disease. The aim of this study was to evaluate the diagnostic utility of delayed postcontrast 3D FLAIR images and a color map of fused postcontrast FLAIR and constructive interference steady state (CISS) images in the identification of endolymphatic hydrops in patients with clinically diagnosed Meniere's disease. STUDY DESIGN: Case control, blinded study. SETTING: Tertiary referral center. PATIENTS: Ten patients with Meniere's disease and five volunteer controls. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Two neuroradiologists blinded to the clinical history independently evaluated for the presence of endolymphatic hydrops on the images of both inner ears for test and control subjects. Both the standard gray-scale FLAIR images and the fused color map images were independently reviewed. RESULTS: The gray-scale 3D FLAIR images demonstrated 68.2% sensitivity and 97.4% specificity, and the fused color map images demonstrated 85.0% sensitivity and 88.9% specificity in the identification of endolymphatic hydrops in Meniere's disease. There was significant correlation between the gray-scale 3D FLAIR images and fused color map images with the categorization of involvement (p = 0.002). Inter-evaluator reliability was excellent (kappa = 0.83 for gray-scale images, kappa = 0.81 for fused color map). CONCLUSION: Delayed 3D FLAIR and fused 3D FLAIR-CISS color map images of the inner ears after intravenous contrast administration are potentially useful diagnostic tools in the evaluation of patients with suspected Meniere's disease.

Background: Impaired NMDA receptor signaling is believed to contribute to schizophrenia and other psychiatric disorders. NMDA receptors are critical for neural development as well as learning, memory, and cognitive processes in adults. Thus disruption of NMDA receptor activation and synaptic transmission might lead to schizophrenia. Drugs that act as NMDA receptor antagonists (e.g., ketamine) lead to schizophrenic-like symptoms, and human genetic studies have highlighted de novo mutations in NMDA receptors and associated proteins in humans with schizophrenia. However, little is known about how NMDA receptor activation is directly involved in cognitive processes such as perception and memory. Here I will present new work in mouse models showing the connections between a gene implicated in schizophrenia (CNTNAP2), NMDA receptor activation, and control of local circuit dynamics by synaptic plasticity and regulation of excitatory-inhibitory balance in mouse sensory cortex. Methods: We performed electrophysiological experiments in brain slices and in vivo. Some behavioral experiments to examine perception and seizures were also performed. For in vitro experiments, brain slices of wild-type and Cntnap2 mutant animals were made. Synaptic transmission (strength of inhibition relative to strength of excitation) and long-term synaptic plasticity (pairing pre- and postsynaptic spikes to examine spike-timing-dependent plasticity) were assessed with whole-cell current-clamp and voltage-clamp recordings. Methods are similar to our past studies in brain slices (Froemke et al., Nature 2005; Southwell et al., Science 2010). For in vivo experiments, animals were anesthetized and head-fixed, and whole-cell recordings made in auditory or visual cortex. Sensory stimuli (pure tones/vocalizations or light flashes/ sequences, respectively) were presented to the animals; response strength and short- and long-term plasticity were measured. Methods are similar to our past studies in vivo (Froemke et al., Nature 2007; Froemke et al., Nature Neurosci 2013). Results: In Cntnap2 mutant animals, we found that: 1) NMDA receptor amplitude was decreased relative to AMPA receptor transmission, 2) long-term synaptic plasticity was impaired, 3) GABAergic inhibition was imbalanced and uncorrelated to excitation, and 4) sensory responses were unreliable and more variable than in wild-type animals. Each of these latter results (#2-4) might come as a direct consequence of impaired NMDA receptor activation (#1). However, treatment with D-serine could selectively rescue and boost NMDA receptor currents in Cntnap2 mutant mice, suggesting that glycine site modulation could improve synaptic and local circuit function in these animals. Conclusions: Many of the disruptions in Cntnap2 mutant mice (serving as a genetic model of schizophrenia) could have as a root cause reductions in current flux through NMDA receptors. However, glycine site agonists may provide a reasonable therapeutic approach for enhancing NMDA receptor function and improving cognitive processes, especially in the context of trainingbased approaches to recruit mechanisms of longterm synaptic plasticity and rebalancing inhibition with excitation

BACKGROUND:Cosmesis is of increasing importance to the otolaryngology patient population. This is the first report of clinical outcomes of robot-assisted neck dissection by North American groups. METHODS:This is a retrospective case-control study. Cases included three patients who underwent isolated, ipsilateral robot-assisted neck dissection. Operative time, estimated blood loss, lymph node retrieval, total drainage, hospital stay and complications from this group were compared against the outcomes of six consecutive patients who underwent conventional neck dissection. RESULTS:Operative times were longer in robot-assisted neck dissection (mean 234 min) compared with the conventional neck dissection (mean 110 min). There were no significant differences between the two groups in other outcomes. CONCLUSIONS:Robot-assisted selective neck dissection of levels II-IV is feasible through a modified facelift incision. Our initial data suggest that this procedure is surgically sound. It should be applied by experienced surgeons who wish to avoid a cervical incision.

BACKGROUND:Pharyngeal stenosis is a complication of head and neck cancer and sleep apnea treatment that results in functional impairment. Due to the location of the stenosis and tendency to recur, surgical management is challenging. Robotic surgery may allow these areas to be treated with surgical technique that would be difficult using traditional approaches. METHODS:A retrospective chart review was performed to identify patients who underwent transoral robotic surgery (TORS) for pharyngeal stenosis at a tertiary hospital system. RESULTS:Five patients were identified, ages 8-75 years. Length of follow-up ranged from 1-12 months. There was one failure, a 74 year old male with a history of chemoradiation to the area who has required additional procedures. CONCLUSION/CONCLUSIONS:TORS may offer improved surgical access to the pharynx in patients who require complex reconstruction that would otherwise be very difficult. Appropriate patient selection is necessary and long-term follow-up is warranted for the selected cases.

BACKGROUND: It is desirable to detect neoplastic thyroid disease before proceeding with surgical therapy for hyperparathyroidism so that both conditions can be treated with a single operation. METHODS: Between March 1998 and June 2009, 227 patients with primary hyperparathyroidism were treated with surgical therapy. Of these, 217 were evaluated preoperatively with a modified 4-dimensional CT and ultrasonography. The medical records of these patients were reviewed in order to document the incidence and significance of thyroid pathology in this cohort of patients. RESULTS: Thyroid nodules were identified in 159 of the 217 patients (73.3%). Nine of 217 patients (4.1%) were treated with either a partial or a total thyroidectomy at the time of parathyroidectomy. Three of these patients had papillary thyroid carcinoma, 1 had a Hurthle cell carcinoma, and 1 had an incidental micropapillary thyroid carcinoma. CONCLUSION: The rate of clinically significant thyroid malignancy in patients undergoing surgical treatment of primary hyperparathyroidism was 1.8%.