Faculty Bibliography

PURPOSE: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is recognized as a significant predictor of outcome. PNI is associated with locoregional recurrence and decreased survival of patients with head and neck SCC. Nerve growth factor (NGF) has been shown to be involved in PNI in several malignancies, including breast, prostate, and pancreatic cancers. We investigated the hypothesis that NGF and its high-affinity receptor tyrosine kinase A (TrkA) are highly expressed in cases of oral SCC that have histologic evidence of PNI. MATERIALS AND METHODS: We performed immunohistochemistry on archived oral tongue SCC specimens from the established oral and general pathology databases at the University of California, San Francisco. The following groups were evaluated: 1) 21 T1/T2 oral tongue SCC cases with PNI and 2) 21 T1/T2 oral tongue SCC cases without histologic evidence of PNI. RESULTS: Strong homogeneous cytoplasmic staining for NGF and TrkA was detected in the malignant cells in the PNI-positive group of tumors. In group II (PNI negative) NGF and TrkA were detected in the stroma cells or were very weakly expressed by the malignant cells. We were able to show the presence of NGF and TrkA in the cytoplasm of malignant squamous cells in tumors with histologic evidence of PNI. Immunostaining for NGF (P = .0001) and TrkA (P = .039) was significantly higher in the PNI-positive oral SCC group than in the PNI-negative oral SCC group. CONCLUSION: This study shows that oral SCC with evidence of PNI shows increased expression of NGF and TrkA and suggests that NGF and TrkA are involved with the mechanism leading to PNI. Further investigations are warranted to determine the potential for use of NGF and TrkA as candidate biomarkers to predict progression and outcome

Ongoing and breakthrough pain is a primary concern for the cancer patient. Although the etiology of cancer pain remains unclear, animal models of cancer pain have allowed investigators to unravel some of the cancer-induced neuropathologic processes that occur in the region of tumor growth and in the dorsal horn of the spinal cord. Within the cancer microenvironment, cancer and immune cells produce and secrete mediators that activate and sensitize primary afferent nociceptors. Pursuant to these peripheral changes, nociceptive secondary neurons in spinal cord exhibit increased spontaneous activity and enhanced responsiveness to three modes of noxious stimulation: heat, cold, and mechanical stimuli. As our understanding of the peripheral and central mechanisms that underlie cancer pain improves, targeted analgesics for the cancer patient will likely follow

This case study presents a report of inflammatory pseudotumor of the inner ear in a child, discusses radiographic findings and clinical management, and reviews the current literature on this rare disease. A 2.5-year-old presented with otalgia, transient vertigo, and fluctuating facial palsy partially responsive to myringotomy with tube. Work-up for infectious and neoplastic processes was negative. Computed tomography (CT) of the temporal bone showed a very unusual, expansile, erosive appearance to the otic capsule, and magnetic resonance imaging of the temporal bone revealed soft tissue enhancement of the middle ear, mastoid, and inner ear. The patient's symptoms were transiently responsive to tympanomastoidectomy. Inner ear histopathology after labyrinthectomy revealed changes consistent with pseudotumor. Inflammatory pseudotumor of the inner ear is extremely rare but needs to be considered in cases of refractory otitis media with facial palsy, particularly when certain changes appear on CT of the temporal bone.

OBJECTIVE:The objectives of this study were to 1) evaluate anatomical relationships and 2) develop technical correlates for endoscopic anterior skull base (ASB) surgery. STUDY DESIGN/METHODS:Cadaver study. SETTING/METHODS:Minimally invasive surgery laboratory. SUBJECTS AND METHODS/METHODS:Ten adult fresh-frozen cadaver heads were dissected from December 2006 to December 2007. The endoscopic trans-cribriform, trans-ethmoid approach to the anterior cranial base was refined over these consecutive dissections. Endoscopic orientation along the ventral axis was assessed with 0 degrees , 30 degrees , and 70 degrees rigid telescopes. Anatomical dimensions of the ASB window were measured in the anteroposterior (posterior table of frontal sinus to planum sphenoidale) and transverse (orbit-to-orbit) dimensions at the anterior ethmoid artery (AEA) and posterior ethmoid artery (PEA). RESULTS:Endoscopic cadaveric dissections confirmed technical feasibility of ASB surgery and greatly enhanced understanding of ASB anatomical concepts. The 30 degrees rigid endoscope provided the most optimal view from the frontal sinus to the planum sphenoidale with the least distortion, relative to 0 degrees and 70 degrees scopes. Careful identification of the AEA and PEA was requisite for proper orientation at the ASB. The posterior one third of the ASB was thickest and always required drilling for resection. The mean boundaries of the ASB window were 33.7 mm (anterior to posterior) and 23.5 and 19.1 mm at the AEA and PEA (orbit to orbit), respectively. CONCLUSION/CONCLUSIONS:This prospective cadaveric study outlined key correlates for endoscopic ASB surgery. It serves to highlight the requisite technical steps and anatomical dimensions when the trans-nasal endoscopic route is employed for ASB pathology.

BACKGROUND: Xeroderma pigmentosum, an autosomal recessive disease that occurs with a frequency of 1:250,000, is caused by a genetic defect in nucleotide excision repair enzymes. Mutation of these enzymes leads to the development of multiple basal cell and squamous cell carcinomas. OBJECTIVES: We present a case of xeroderma pigmentosum in a patient with cervical and intraparotid metastatic disease from recurrent cutaneous squamous cell carcinomas of the face and scalp, treated with neck dissection and re-irradiation. With the illustrative case report, we include a literature review of diagnosis, prognostic factors, and treatment, with emphasis on surgical and radiation treatment of cervical metastatic disease from recurrent skin carcinomas. CASE PRESENTATION: A xeroderma pigmentosum patient presented to our clinic with a 2-cm right submental and 1-cm right infra-auricular mass after resection of multiple squamous cell carcinomas of the scalp and face, and external-beam radiation therapy to the right face and neck. Fine-needle aspiration biopsy of the submental mass revealed poorly differentiated squamous cell carcinoma. The patient was brought to the operating room for a right modified radical neck dissection and excision of the right submental and intraparotid mass. Surgical pathology revealed 3 level ia and supraclavicular lymph nodes that were positive for metastatic squamous cell carcinoma. Re-irradiation to the entire right hemi-neck and left submandibular nodal region was performed using opposed oblique portals for the upper neck and a low anterior en face hemi-neck portal. The left parotid region was also included in the re-irradiation volume. Treatment was completed without delayed complications or recurrences to date. CONCLUSIONS: To our knowledge, this is the first case report in the literature of a patient with xeroderma pigmentosum who subsequently developed metastatic disease from recurrent cutaneous squamous cell carcinoma. Because of the rarity of xeroderma pigmentosum, this case report is also the first to describe re-irradiation to treat cervical and intraparotid metastatic disease in a xeroderma pigmentosum patient

OBJECTIVES: The purpose of this study is to determine how combinations of noise levels and reverberation typical of ranges found in current classrooms will affect speech recognition performance of typically developing children with normal speech, language, and hearing and to compare their performance with that of adults with normal hearing. Speech recognition performance was measured using the Bamford-Kowal-Bench Speech in Noise test. A virtual test paradigm represented the signal reaching a student seated in the back of a classroom with a volume of 228 m and with varied reverberation time (0.3, 0.6, and 0.8 sec). The signal to noise ratios required for 50% performance (SNR-50) and for 95% performance were determined for groups of children aged 6 to 12 yrs and a group of young adults with normal hearing. DESIGN: This is a cross-sectional developmental study incorporating a repeated measures design. Experimental variables included age and reverberation time. A total of 63 children with normal hearing and typically developing speech and language and nine adults with normal hearing were tested. Nine children were included in each age group (6, 7, 8, 9, 10, 11, and 12 yrs). RESULTS: The SNR-50 increased significantly with increased reverberation and decreased significantly with increasing age. On average, children required positive SNRs for 50% performance, whereas thresholds for adults were close to 0 dB or <0 dB for the conditions tested. When reverberant SNR-50 was compared with adult SNR-50 without reverberation, adults did not exhibit an SNR loss, but children aged 6 to 8 yrs exhibited a moderate SNR loss and children aged 9 to 12 yrs exhibited a mild SNR loss. To obtain average speech recognition scores of 95% at the back of the classroom, an SNR > or = 10 dB is required for all children at the lowest reverberation time, of > or = 12 dB for children up to age 11 yrs at the 0.6-sec reverberant condition, and of > or = 15 dB for children aged 7 to 11 yrs at the 0.8-sec condition. The youngest children require even higher SNRs in the 0.8-sec condition. CONCLUSIONS: Results highlight changes in speech recognition performance with age in elementary school children listening to speech in noisy, reverberant classrooms. The more reverberant the environment, the better the SNR required. The younger the child, the better the SNR required. Results support the importance of attention to classroom acoustics and emphasize the need for maximizing SNR in classrooms, especially in classrooms designed for early childhood grades

A retrospective study was conducted to assess outcomes of reconstruction of the oral cavity with the platysma myocutaneous flap, in terms of flap survival, complications, and quality of life. Included were 10 patients with squamous cell carcinoma (stage T1 to T4; nodal status N0 to N2) of the oral cavity who were treated between 2002 and 2006. Each patient underwent tumor resection, modified radical neck dissection, and primary reconstruction with a platysma myocutaneous flap. Operating time, length of stay, time to swallow, and complications were assessed, and the University of Washington Quality of Life questionnaire was administered. Mean operating time was <4 hours, mean length of stay was 11 days, and mean time to swallow was 9 days. One patient had distal flap necrosis and one had wound dehiscence. No total flap failures or fistulas occurred. The authors conclude that the platysma myocutaneous flap provides thin, pliable, reliable tissue for use in the oral cavity. The additional operating room time is negligible, the surgical complications minimal, and the overall quality of life very good. This flap should be used more frequently in the reconstruction of oral cavity defects

OBJECTIVES/HYPOTHESIS: To assess the current state of mentorship in otolaryngology residency. STUDY DESIGN: Internet-based anonymous survey of chief residents in otolaryngology residency. METHODS: Nonidentifying demographic information, career plans, and general questions about residency experience were queried. Participants were asked to rate their mentorship experience in general and specifically with regard to research, personal quality of life, and career preparation. Responses were scored using a five-point ordinal Likert scale, with higher scores representing more favorable responses. RESULTS: The survey was completed by 47 (17.2%) respondents. Eighteen respondents (38%) were assigned an official faculty mentor, and 23 respondents (49%) were assigned a research mentor during their residency. Thirty-nine respondents (83%) reported receiving meaningful mentorship from faculty who were not officially assigned mentors. Overall, 18 respondents (38%) were neutral or not satisfied with the mentorship they received during residency. Statistically significant higher scores were noted for mentorship in career preparation (median, 4) versus mentorship in research (median, 4; P < .001) and resident quality of life (median, 3; P < .001). Lower scores were noted for availability of mentorship in preparation for a career in private practice versus academic medicine (median, 4 vs. 5; P < .001). Residents who were officially assigned mentors reported statistically significant higher scores with regard to satisfaction with the overall mentorship experience (median, 4 vs. 3; P = .05) and different aspects of mentorship in career preparation and research training. CONCLUSIONS: The current study reveals variability in the mentorship experience in otolaryngology residency. Potential deficiencies may exist, including absence of formal mentorship in some residency programs. Increased attention to mentorship, especially with regard to research, career preparation, and quality of life may improve the overall residency experience.

Endobronchial ultrasonography (EBUS) has emerged as a new diagnostic tool that allows the bronchoscopist to see beyond the airway, including pulmonary and mediastinal lesion. The real time EBUS-guided transbronchial needle aspiration (TBNA) has advanced the diagnostic yield in primary lung pathology and mediastinal lymph node staging of lung carcinoma. Sixty-four patients (36 males, 28 females, ages ranging from 16 to 86 years) with peribronchial lung lesions and mediastinal and/or hilar lymph node lesions underwent EBUS-TBNA. All patients had intraoperative cytological assessment by smears on aspiration samples or touch preparation on needle core biopsies.The cytological final diagnoses were categorized as negative, suspicious/positive, and non-diagnostic. Forty-nine samples were obtained from lymph node lesions and 15 samples were obtained from lung lesions. In cytology specimens, 32 patients had suspicious/positive diagnoses and 32 patients had negative diagnosis. In follow-up histology specimens, 35 patients had malignant diagnoses, including 18 adenocarcinomas, 8 small cell carcinomas, 6 squamous cell carcinomas, 1 metastatic hepatocellular carcinoma, 1 metastatic melanoma, and 1 lymphoma. Twenty-nine patients had negative diagnoses. Sensitivity and specificity were 88.9% and 96.4%, respectively. Positive and negative predictive values were 97.0% and 87.1%, respectively. Diagnostic accuracy was 92.2%. EBUS-TBNA is an efficient and effective technique for diagnosis of intrapulmonary and mediastinal/hilar lymph nodes. It becomes significantly invaluable on clinical management for staging in those patients with lung cancer of other metastatic malignancies. This technique enables us to obtain tissue samples for quick diagnoses beyond central airway with minimal complications. Diagn. Cytopathol. 2010. (c) 2009 Wiley-Liss, Inc