Faculty Bibliography

Recent advances in surgery and orthodontics have resulted in improvements in the management of patients with a cleft lip or palate. Early surgical intervention and bone-grafting procedures have frequently been used to ensure closure of the cleft and continuity of the alveolar bone. However, a need for the prosthodontic management of patients with a cleft palate still exists. Most frequently, the indication is to restore the edentulous spaces located anteriorly in the vicinity of the residual cleft defect. In addition to improving the esthetic outcome, prosthodontic management also is required to restore function, especially occlusion and speech. This clinical report illustrates the management of an adult patient with a unilateral cleft of the lip and palate who required prosthodontic rehabilitation after surgery. The patient had previously undergone multiple surgeries and did not want to consider implant therapy as a treatment option. Thus, the patient was managed with fixed and removable prosthodontics with a maxillary overdenture prosthesis retained by microextracoronal resilient attachments, which were laser welded onto crowns on abutment teeth to obtain a functionally and esthetically acceptable result.

OBJECTIVE: To determine the prevalence of otolith dysfunction in patients with refractory benign paroxysmal positional vertigo (BPPV). STUDY DESIGN: Unmatched case control. SETTING: Tertiary care institution. SUBJECTS AND METHODS: Patients included were diagnosed with BPPV, failed initial in-office canalith repositioning maneuvers (CRMs), and completed vestibular testing and vestibular rehabilitation (n = 40). Refractory BPPV (n = 19) was defined in patients whose symptoms did not resolve despite vestibular rehabilitation. These patients were compared with a control group of those with nonrefractory BPPV (n = 21) for results of a caloric test, cervical vestibular evoked myogenic potential (cVEMP), and subjective visual vertical (SVV). RESULTS: Forty-six of 251 patients failed initial treatment with in-office CRM. Forty patients met inclusion criteria. There was no significant difference between the cases (refractory BPPV) (n = 19) and controls (nonrefractory BPPV) (n = 21) in terms of age, duration of symptoms, laterality of BPPV, and BPPV symptoms. There was no difference in the prevalence of caloric weakness and cVEMP abnormalities (P > .05), with odds ratios (ORs [95% confidence interval (CI)]) of having abnormal results among cases vs controls of 1.1818 (0.3329-4.1954) and 4.3846 (0.7627-25.2048), for caloric and cVEMP, respectively. Abnormal eccentric SVV was more prevalent in refractory BPPV cases (58%) than in controls (14%) (P < .0072). The OR (95% CI) of having abnormal SVV was 8.25 (1.7967-37.8822) higher among patients with refractory BPPV than those with nonrefractory BPPV. CONCLUSION: Patients with refractory BPPV are more likely to have abnormal eccentric SVV and thus underlying utricular dysfunction. This finding is important to take into account when designing rehabilitation strategies for patients with BPPV who fail CRM.

BACKGROUND:Patient characteristics, risk factors, and microbiology are important to consider in the management of complications of acute bacterial sinusitis (ABS) in pediatric patients. This study evaluates this subset of patients and compares them to patients that undergo surgery for chronic rhinosinusitis (CRS). METHODS:This study is a retrospective review of all pediatric patients from 2002 to 2011, who underwent sinus surgery at a tertiary hospital. Patients who underwent surgery for ABS complication were compared to patients who underwent surgery for CRS. Statistical analysis was completed using chi-square test or Fisher's exact test with a statistical significance set at p<0.05. RESULTS:Twenty-seven patients with a complication of ABS and 77 patients with CRS were analyzed. The groups did not differ demographically. Patients with a complication were statistically less likely to have seasonal allergies, prior sinusitis, prior nasal steroid use, or adenoidectomy (p<0.05). In addition, they had more frequent involvement of ethmoid and frontal sinuses (p<0.05). The most common cultures results were no growth (30.8%), Streptococcus milleri (30.8%), and normal flora (19.2%) in ABS for the with a complication group, and normal flora (41.5%), coagulase negative Staphylococcus (22%), and Propionobacterium (19.5%) for the CRS group. Most prevalent complications were preseptal cellulitis (55.5%), orbital subperiosteal abscess (29.6%), subgaleal abscess (22%), and epidural abscess (22%). Five patients had simultaneous orbital and intracranial complications. CONCLUSIONS:Patients who present with complications of ABS vary significantly from the CRS patients. Location of most commonly affected sinuses and microbiology also differ and is crucial for understanding the management of this disease process.

Endoscopic endonasal surgery has been established as the safest approach to pituitary tumors, yet its role in other common skull base lesions has not been established. To answer this question, we carried out a systematic review of reported series of open and endoscopic endonasal approaches to four major skull base tumors: olfactory groove meningiomas (OGM), tuberculum sellae meningiomas (TSM), craniopharyngiomas (CRA), and clival chordomas (CHO). Data from 162 studies containing 5,701 patients were combined and compared for differences in perioperative mortality, gross total resection (GTR), cerebrospinal fluid (CSF) leak, neurological morbidity, post-operative visual function, post-operative anosmia, post-operative diabetes insipidus (DI), and post-operative obesity/hyperphagia. Weighted average rates for each outcome were calculated using relative study size. Our findings indicate similar rates of GTR and perioperative mortality between open and endoscopic approaches for all tumor types. CSF leak was increased after endoscopic surgery. Visual function symptoms were more likely to improve after endoscopic surgery for TSM, CRA, and CHO. Post-operative DI and obesity/hyperphagia were significantly increased after open resection in CRA. Recurrence rates per 1,000 patient-years of follow-up were higher in endoscopy for OGM, TSM, and CHO. Trends for open and endoscopic surgery suggested modest improvement in all outcomes over time. Our observations suggest that endonasal endoscopy is a safe alternative to craniotomy and may be preferred for certain tumor types. However, endoscopic surgery is associated with higher rates of CSF leak, and possibly increased recurrence rates. Prospective study with long-term follow-up is required to verify these preliminary observations.

A number of viral infections can cause hearing loss. Hearing loss induced by these viruses can be congenital or acquired, unilateral or bilateral. Certain viral infections can directly damage inner ear structures, others can induce inflammatory responses which then cause this damage, and still others can increase susceptibility or bacterial or fungal infection, leading to hearing loss. Typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing losses can be seen following infection with certain viruses. Occasionally, recovery of hearing after these infections can occur spontaneously. Most importantly, some of these viral infections can be prevented or treated. For many of these viruses, guidelines for their treatment or prevention have recently been revised. In this review, we outline many of the viruses that cause hearing loss, their epidemiology, course, prevention, and treatment.

It is currently unclear whether Merlin/NF2 suppresses tumorigenesis by activating upstream components of the Hippo pathway at the plasma membrane or by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. We found that derepressed CRL4(DCAF1) promotes YAP- and TEAD-dependent transcription by ubiquitylating and, thereby, inhibiting Lats1 and 2 in the nucleus. Genetic epistasis experiments and analysis of tumor-derived missense mutations indicate that this signaling connection sustains the oncogenicity of Merlin-deficient tumor cells. Analysis of clinical samples confirms that this pathway operates in NF2-mutant tumors. We conclude that derepressed CRL4(DCAF1) promotes activation of YAP by inhibiting Lats1 and 2 in the nucleus.

In this era of globalization and rapid advances in radiation oncology worldwide, the American Society for Radiation Oncology (ASTRO) is committed to help decrease profound regional disparities through the work of the International Education Subcommittee (IES). The IES has expanded its base, reach, and activities to foster educational advances through a variety of educational methods with broad scope, in addition to committing to the advancement of radiation oncology care for cancer patients around the world, through close collaboration with our sister radiation oncology societies and other educational, governmental, and organizational groups.

INTRODUCTION: It is known that physicians sometimes recommend treatment that, in a similar clinical scenario, they might not choose for themselves. We sought to understand this dynamic across cerebrovascular practice and examine how neurosurgeons value the procedures they offer. METHODS: We conducted an online survey sent to a large cohort of neurosurgeons in May 2013. Respondents were randomised to answer either as the surgeon or as the patient. The questions involved patients presenting with 1) an epidural hematoma (control), 2) un-ruptured anterior communicating artery aneurysm, 3) incidentally found right temporal AVM, 4) spontaneous intracranial and intraventricular haemorrhage in deep structure. Data on practice parameters and experience levels was also collected. RESULTS: We obtained 534 survey responses, 279 responding as the "neurosurgeon", and 255 as the "patient," with a response rate of 19.7%. Demographics amongst the two groups of survey takers was similar. There was no difference in the management of an epidural hematoma, as expected. For the unruptured aneurysm, the rates of opting for treatment was similar amongst respondees. However within the treatment group there was a trend for survey takers to more often chose coiling for themselves and clipping for patients (p = 0.056). Surgeons, however, with a greater than 30% open-cerebrovascular practice had less of a tendency to do so. For arteriovenous malformation management, there was no statistical difference between choosing treatment or conservative management. However, amongst the respondees who chose treatment, more respondees chose resection/embolization for their patient but radiosurgery for self (p = 0.001). In a case of a large spontaneous intracranial and intraventricular haemorrhage neurosurgeons were more likely to place a ventricular drain in a patient than himself or herself. Neurosurgeons in practice more than 10 years since residency were more likely to recommend against interventions for aneurysms, AVMs or intracranial haemorrhage. CONCLUSIONS: In the majority of cases altering the role of the surgeon did not change the decision to pursue treatment or conservative treatment. In certain clinical scenarios, however, neurosurgeons choose treatment options for themselves that are different than what they would choose for their patients. For the management of an arteriovenous malformations, intracranial aneurysms, and hypertensive haemorrhage, responses favored less invasive interventions when the surgeon was the patient. These findings are likely a result of cognitive biases, previous training, experience, areas of expertise, and personal values. DISCLOSURES: O. Tanweer: None. T. Wilson: None. S. Kalhorn: None. J. Golfinos: None. P. Huang: None. D. Kondziolka: None.

Tumor cell survival consists of an intricate balance between cell growth and cell death pathways involving receptor tyrosine kinases [RTK; i.e., HER1-4, insulin-like growth factor-1 receptor (IGF-1R), etc.], MDM2, and the tumor suppressor proteins phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p53. We recently demonstrated that shedded E-cadherin extracellular domain fragment (sEcad) is a valid oncogenic target that is significantly increased in human clinical skin squamous cell cancers (SCC) samples, UV-induced mouse tumors, and cells and promotes tumor cell proliferation, migration, and invasion by interacting and activating with the HER-phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) axis. In resected human SCC tumors, we reported enhanced sEcad-HER1, sEcad-HER2, and sEcad-IGF-1R, but not FL-Ecad-RTK interactions. Here, we demonstrate that a sEcad antibody against the ectodomain of E-cadherin suppressed SCC growth and increased tumor differentiation in orthotopic cutaneous SCC xenografts by inhibiting proliferation and inducing apoptosis. A similar anti-sEcad antibody-induced inhibition of proliferation and induction of cell death was evident in PAM212 cells in vitro. Mechanistically, anti-sEcad administration upregulated an array of cell death pathways (i.e., Bad, active caspase-3, and cleaved PARP) and inhibited inhibitors of apoptosis (IAP; survivin, livin, etc.), RTKs (HER1, HER2, p95HER2, and IGF-1R), MAPK and PI3K/mTOR prosurvival signaling. Interestingly, in anti-sEcad mAb-treated tumors and PAM212 cells, this effect was associated with a profound increase in membrane, cytosolic, and nuclear levels of PTEN; enhanced cytosolic p53; and a decrease in MDM2 levels. Overall, our studies suggest that an antibody-based therapy against sEcad may be a novel therapeutic platform for cutaneous SCCs by hampering key proto-oncogenes (RTKs, IAPs, and MDM2) and activating potent tumor suppressor proteins (PTEN and p53) intricately linked to tumor growth and survival.