Faculty Bibliography

IMPORTANCE:Management of cervical unknown primary squamous cell carcinoma (CUP) has evolved with the introduction of transoral robotic surgery (TORS). OBJECTIVES:1. To describe the efficacy of TORS lingual and palatine tonsillectomy in identifying the primary site of malignancy. 2. To explore how the extent of surgery affects diagnostic yield. 3. To report margin status of TORS resections. DESIGN, SETTING AND PARTICIPANTS:A retrospective, single-center cohort study utilizing a prospectively collected database of CUP patients in a high-volume tertiary referral center. Patient underwent operative laryngoscopy plus TORS as clinically indicated. MAIN OUTCOMES AND MEASURES:Primary end point was successful identification of the primary. The extent of surgery and margin status were also examined. RESULTS:From 2010-2016, 64 patients with CUP were treated. The primary tumor was found in 51 patients (80%). Fourteen patients (22%) were identified with operative laryngoscopy alone. Fifty patients underwent TORS lingual tonsillectomy ± palatine tonsillectomy with 37 primary tumors identified (74%). The primary was located in the lingual tonsil in 32 patients (86%) and palatine tonsil in 5 patients (10%, p<0.001). Negative margins were achieved in 19 patients (51%). The deep margin was the most commonly positive margin (47%, p=0.049). CONCLUSION AND RELEVANCE:Operative laryngoscopy with TORS is efficacious, localizing the primary in 80% of patients. If a margin was positive, it was most commonly the deep margin. This study provides valuable information that can help standardize surgical technique, further increasing the diagnostic yield and decreasing the negative margin rate of TORS for CUP.

BACKGROUND: Cochlear implants (CIs) successfully restore hearing in postlingually deaf adults, but in doing so impose a frequency-position function in the cochlea that may differ from the physiological one. PURPOSE: The CI-imposed frequency-position function is determined by the frequency allocation table programmed into the listener's speech processor and by the location of the electrode array along the cochlea. To what extent can postlingually deaf CI users successfully adapt to the difference between physiological and CI-imposed frequency-position functions? RESEARCH DESIGN: We attempt to answer the question by combining behavioral measures of electroacoustic pitch matching (PM) and measures of electrode location within the cochlea. STUDY SAMPLE: The participants in this study were 16 adult CI users with residual hearing who could match the pitch of acoustic pure tones presented to their unimplanted ears to the pitch resulting from stimulation of different CI electrodes. DATA COLLECTION AND ANALYSIS: We obtained data for four to eight apical electrodes from 16 participants with CIs (most of whom were long-term users), and estimated electrode insertion angle for 12 of these participants. PM functions in this group were compared with the two frequency-position functions discussed above. RESULTS: Taken together, the findings were consistent with the possibility that adaptation to the frequency-position function imposed by CIs does happen, but it is not always complete. CONCLUSIONS: Some electrodes continue to be perceived as higher pitched than the acoustic frequencies with which they are associated despite years of listening experience after cochlear implantation.

While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy-related inflammation proven by brain biopsy, she was treated successfully with immunosuppression.

BACKGROUND: Most head and neck (H&N) cancer patients receive high-dose external beam radiation therapy (RT), often in combination with surgery and/or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on the oral and maxillofacial tissues, some of which persist for the life of the patient. However, dental management of these patients is based largely on individual and expert opinion, as few studies have followed patients prospectively to determine factors that predict adverse oral sequelae. In addition, many previous studies were conducted before wide-spread adoption of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. The objective of this multi-center study is to systematically evaluate the oral health of subjects for 2 years after commencement of RT, with the goal of identifying risk factors that predict adverse oral outcomes post-RT. METHODS: This is a prospective multi-center longitudinal cohort study of H&N cancer patients who receive high-dose RT with curative intent. Planned enrollment is 756 subjects at 6 primary clinical sites (and their affiliated sites) in the USA. A baseline visit is conducted prior to the beginning of RT. Follow-up visits are conducted at 6, 12, 18 and 24 months from the start of RT. The primary outcome measure is the 2-year rate of tooth loss in patients who have received at least one session of external beam RT for H&N cancer. Secondary outcome measures include the incidence of exposed intraoral bone; incidence of post-extraction complications; change in Decayed Missing and Filled Surfaces (DMFS); change in periodontal measures; change in stimulated whole salivary flow rates; change in mouth opening; topical fluoride utilization; chronic oral mucositis incidence; changes in RT-specific quality of life measures; and change in oral pain scores. DISCUSSION: This study will contribute to a better understanding of the dental complications experienced by these patients. It will also enable identification of risk factors associated with adverse outcomes such as tooth loss and osteoradionecrosis. These findings will support the development of evidence-based guidelines and inform the planning of future interventional studies, with the goal of advancing improvements in patient care and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02057510 , registered 5 February 2014.

Craniofacial surgeons perform operations that involve exposure of the dura. Typical procedures include cranial vault remodeling (CVR), fronto-orbital advancement (FOA), Le Fort III, monobloc, bipartition advancement, or distraction. Cerebrospinal fluid (CSF) fistulas remain one of the most common complications encountered, occurring in up to 30% of patients. Cerebrospinal fluid fistulas can be encountered intraoperatively, acutely, or in the late postoperative period. Traditional management has been well described in the neurosurgical literature. While several studies of complications exist, there is a relative lack of adequate information for craniofacial surgeons. The authors review current literature and provide 3 patients to illustrate our management paradigm.The authors review 30 years of experience at our institution and the pertinent literature. The mean rate of CSF fistula was 11.2%; rates were lowest for FOA/CVR, 5.5%. Patients with fistulas persisting after 2 days of conservative therapy or whom were symptomatic prompted placement of a lumbar subarachnoid catheter. Failure of the leak to resolve with CSF diversion prompted exploration and therapy which could include a patch, pericranial flap, and/or endonasal repair with septal flaps. Three patients are used to illustrate the paradigm, all of which have had no recurrence thus far.Cerebrospinal fluid fistula remains one of most common complications craniofacial surgeons encounter. Although neurosurgeons are often part of the clinical team, the craniofacial surgeon should be familiar with all aspects of treatment. Prompt diagnosis and appropriate knowledgeable management may avoid morbidity and mortality.

Behavioural engagement can enhance sensory perception. However, the neuronal mechanisms by which behavioural states affect stimulus perception remain poorly understood. Here we record from single units in auditory cortex of rats performing a self-initiated go/no-go auditory task. Self-initiation transforms cortical tuning curves and bidirectionally modulates stimulus-evoked activity patterns and improves auditory detection and recognition. Trial self-initiation decreases the rate of spontaneous activity in the majority of recorded cells. Optogenetic disruption of cortical activity before and during tone presentation shows that these changes in evoked and spontaneous activity are important for sound perception. Thus, behavioural engagement can prepare cortical circuits for sensory processing by dynamically changing sound representation and by controlling the pattern of spontaneous activity.

Balance arises from the interplay of external forces acting on the body and internally generated movements. Many animal bodies are inherently unstable, necessitating corrective locomotion to maintain stability. Understanding how developing animals come to balance remains a challenge. Here we study the interplay among environment, sensation, and action as balance develops in larval zebrafish. We first model the physical forces that challenge underwater balance and experimentally confirm that larvae are subject to constant destabilization. Larvae propel in swim bouts that, we find, tend to stabilize the body. We confirm the relationship between locomotion and balance by changing larval body composition, exacerbating instability and eliciting more frequent swimming. Intriguingly, developing zebrafish come to control the initiation of locomotion, swimming preferentially when unstable, thus restoring preferred postures. To test the sufficiency of locomotor-driven stabilization and the developing control of movement timing, we incorporate both into a generative model of swimming. Simulated larvae recapitulate observed postures and movement timing across early development, but only when locomotor-driven stabilization and control of movement initiation are both utilized. We conclude the ability to move when unstable is the key developmental improvement to balance in larval zebrafish. Our work informs how emerging sensorimotor ability comes to impact how and why animals move when they do.

High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management.