Faculty Bibliography

The aim of this study was to validate the published University of California San Francisco (UCSF) Oral Cancer Pain Questionnaire. To test for validity of the questionnaire, 16 patients with oral cancer completed the 8-item questionnaire immediately before and after treatment (surgical resection) of their oral cancer. For all 8 questions, the difference between mean preoperative and mean postoperative responses were statistically significant (P < .05), confirming the validity of the questionnaire to measure oral cancer pain. Internal consistency of the questionnaire was evaluated by using Cronbach's alpha, which provides an estimate of reliability based on all correlations between the items (questions) of the instrument (questionnaire). In the oral cancer pain questionnaire, questions 1, 3, and 5 evaluate the intensity, sharpness, and throbbing nature of pain when the patient is not engaged in oral function (talking, eating, and drinking). Questions 2, 4, and 6 measure the intensity, sharpness, and throbbing nature of pain during oral function. Cronbach's alpha for questions 1, 3, and 5 is 0.87 and Cronbach's alpha for questions 2, 4, and 6 is 0.94; values greater than 0.7 indicate reliability. In this study, we have validated the UCSF Oral Cancer Pain Questionnaire as an effective tool in quantifying pain from oral cancer. PERSPECTIVE: The study validates an oral cancer pain questionnaire. The questionnaire can be used to reliably measure pain levels before and after surgical resection in patients with oral cancer

OBJECTIVE:: To highlight diagnostic and management features of auditory neuropathy/auditory dyssynchrony (AN/DS) due to central demyelinating disorder. PATIENTS:: A child with AN/DS due to central nervous system pathologic findings. INTERVENTIONS:: Audiometry, auditory brainstem response (ABR) test, otoacoustic emission test, magnetic resonance imaging (MRI) with gadolinium contrast, intravenous corticosteroid treatment, antiviral treatment, stereotactic biopsy, and cyclophosphamide immunomodulation. MAIN OUTCOME MEASURES:: Pure-tone audiometry, speech discrimination testing, ABR, and MRI. RESULTS:: A 12-year-old girl presented with acute sensorineural hearing loss, abnormal ABR, and normal otoacoustic emissions consistent with AN/DS. The hearing loss demonstrated fluctuation and corticosteroid responsiveness. Magnetic resonance imaging and stereotactic biopsy revealed brainstem demyelination consistent with multiple sclerosis. Definitive treatment consisted of cyclophosphamide immunomodulation. CONCLUSION:: Although recent focus on pathophysiology of AN/DS has shifted from auditory nerve abnormalities to dyssynchrony within the cochlea, cases associated with fluctuating sensorineural hearing loss and responsiveness to corticosteroid therapy should raise the suspicion of central nervous system pathologic findings. Therefore, it is crucial to obtain brain MRI with contrast enhancement in all patients with AN/DS. This is critical in patients undergoing cochlear implantation because MRI may be contraindicated postoperatively

BACKGROUND: Minimally invasive esophagectomy (MIE) via thoracoscopy and laparoscopy have reduced the morbidity and mortality of total esophagectomy at experienced centers. MIE has not been evaluated in combination with major head and neck surgery, or in the otolaryngology literature. METHODS: Case series of 11 consecutive patients undergoing either open or MIE with an ablative neck procedure. RESULTS: Comparing 4 MIEs and 7 open operations, similar operative time, blood loss, and ICU and hospital length of stay were observed. There was one mortality in the open group. A 100% rate of major complications was observed in the MIE group. CONCLUSION: Our multidisciplinary team was unable to achieve improved outcomes in a series of head and neck surgical patients undergoing MIE. This result may represent an early stage of the learning curve for MIE, but may also be attributed to the escalated surgical requirements of head and neck patients

Receptive fields of sensory cortical neurons are plastic, changing in response to alterations of neural activity or sensory experience. In this way, cortical representations of the sensory environment can incorporate new information about the world, depending on the relevance or value of particular stimuli. Neuromodulation is required for cortical plasticity, but it is uncertain how subcortical neuromodulatory systems, such as the cholinergic nucleus basalis, interact with and refine cortical circuits. Here we determine the dynamics of synaptic receptive field plasticity in the adult primary auditory cortex (also known as AI) using in vivo whole-cell recording. Pairing sensory stimulation with nucleus basalis activation shifted the preferred stimuli of cortical neurons by inducing a rapid reduction of synaptic inhibition within seconds, which was followed by a large increase in excitation, both specific to the paired stimulus. Although nucleus basalis was stimulated only for a few minutes, reorganization of synaptic tuning curves progressed for hours thereafter: inhibition slowly increased in an activity-dependent manner to rebalance the persistent enhancement of excitation, leading to a retuned receptive field with new preference for the paired stimulus. This restricted period of disinhibition may be a fundamental mechanism for receptive field plasticity, and could serve as a memory trace for stimuli or episodes that have acquired new behavioural significance

PURPOSE: To establish the safety and toxicity profile of daily gefitinib with radiation alone or with concurrent chemoradiotherapy in previously untreated patients with locally advanced squamous cell head and neck cancer (LAHNC). PATIENTS AND METHODS: Patients with intermediate-stage LAHNC were treated with concomitant boost radiation (RT) alone with escalating doses of daily gefitinib (250 or 500 mg; cohort I). Once a safety profile was determined with RT alone, patients with high-risk disease were then treated with daily gefitinib (250 or 500 mg), weekly cisplatin (CDDP; 30 mg/m2), and once-daily RT (cohort II). Patients also received post-RT gefitinib at 250 mg daily for a period of up to 2 years. RESULTS: Twenty-three patients were enrolled and assessable for toxicity. No dose-limiting toxicities (DLTs) were observed in patients treated in cohort I at either 250 or 500 mg of gefitinib daily with concomitant boost RT to 72 Gy. In patients receiving chemoradiotherapy and gefitinib (cohort II), DLTs included one grade 4 diarrhea and one grade 4 neutropenic fever. Fifteen patients started maintenance gefitinib, and eight (53%) experienced grade 1 to 2 acne-like skin rash and diarrhea, but no grade 3 or 4 toxicity occurred. CONCLUSION: Gefitinib (250 or 500 mg daily) was well tolerated with concomitant boost RT or concurrent chemoradiotherapy with weekly CDDP. Protracted administration of gefitinib for up to 2 years at 250 mg daily was also tolerated well.

Despite the fact that vocal folds are subjected to extensive mechanical forces, the role of mechanical strain in vocal fold wound healing has been overlooked. Recent studies on other tissues have demonstrated that low physiological levels of mechanical forces are beneficial to injured tissues, reduce inflammation, and induce synthesis of matrix-associated proteins essential for enhanced wound healing. In this study, we speculated that mechanical strain of low magnitudes also attenuates the production of inflammatory mediators and alters the extracellular matrix synthesis to augment wound healing in cultured vocal fold fibroblasts. To test this hypothesis, fibroblasts from rabbit vocal folds were isolated and exposed to various magnitudes of cyclic tensile strain (CTS) in the presence or absence of interleukin-1beta (IL-1beta). Results suggest that IL-1beta activates proinflammatory gene transcription in vocal fold fibroblasts. Furthermore, CTS abrogates the IL-1beta-induced proinflammatory gene induction in a magnitude-dependent manner. In addition, CTS blocks IL-1beta-mediated inhibition of collagen type I synthesis, and thereby upregulates collagen synthesis in the presence of IL-1beta. These findings are the first to reveal the potential utility of low levels of mechanical signals in vocal fold wound healing, and support the emerging on vivo data suggesting beneficial effects of vocal exercise on acute phonotrauma

The success of replicating adenoviruses for cancer therapy is limited by inefficient virus delivery and poor distribution within the tumor mass. Stromal matrix within the tumor may hinder the free cell-to-cell spread of the virus. In this study, in vitro cell culture experiments showed that collagen I blocked the passage of an adenoviral vector through a membrane. On the basis of reports of the effective collagen I-degrading activity of matrix metalloproteinase-8 (MMP-8), we constructed an adenovirus to express the MMP-8 transgene (AdMMP8). A549 cells infected in vitro with AdMMP8 did not show altered growth but were able to modify a fibrillar collagen substrate to allow viral diffusion. Further, AdMMP8 did not affect replication of the wild-type virus (Adwt300). Established human A549 lung cancer and BxPC-3 pancreatic cancer xenograft tumors that were injected with Adwt300 together with the non-replicating AdMMP8 virus showed significantly reduced growth compared with control tumors. Histochemical analysis showed reduced amounts of collagen within necrotic areas of MMP-8-injected tumors compared with controls. These results demonstrate that intra-tumoral expression of MMP-8 is a possible strategy for improving viral spread and improving the oncolytic activity of replicating adenovirus

We examined benign and malignant mesothelial tissue samples for the presence of X-linked inhibitor of apoptosis protein (XIAP), a potent constituent of the inhibitor of apoptosis family of caspase inhibitors. We subjected 55 sections (31 malignant mesotheliomas, 2 well-differentiated peritoneal mesotheliomas, 13 pleural mesothelial hyperplasias, and 9 benign mesothelial tissues) from archival formalin-fixed, paraffin-embedded surgical tissue blocks to citrate-based antigen retrieval and then incubated them with monoclonal anti-XIAP (clone 48, dilution 1:250; BD Biosciences, San Jose, CA) at 4 degrees C for 72 hours and developed them using EnVision-Plus reagents (DAKO, Carpinteria, CA) and diaminobenzidine as the chromogen. Particulate or nonhomogeneous cytoplasmic staining was considered positive. All 9 normal mesothelial samples were negative for XIAP. Of 13 mesothelial hyperplasias, 1 (8%) was weakly positive in fewer than 10% of cells, as was 1 of 2 well-differentiated peritoneal mesotheliomas. Of 31 malignant mesotheliomas, 25 (81%) displayed XIAP positivity. XIAP immunostaining, when strong, allows for distinction of malignant from benign and hyperplastic mesothelial cell populations and is a potentially useful immunodiagnostic marker in small samples and morphologically controversial cases. Elevated expression of XIAP could contribute to tumorigenesis in mesothelioma.

Botulinum toxin A is an effective and safe treatment for perioral rejuvenation. This article explores the application of this toxin for cosmetic use in the perioral region, facial asymmetry, and improved facial wound healing. This article also describes how the use of botulinum toxin A, which has traditionally been used on the upper one third of the face, has expanded to the lower two thirds with the advent of a new formulation that consists of botulinum toxin combined with an anesthetic agent and a vasoconstrictor. The new formula provides the injecting physician with immediate feedback on the eventual treatment effect and reduces local diffusion of the simultaneously injected agents, potentially limiting systemic absorption and diffusion to neighboring muscle groups and adding to an already remarkable safety profile.