George H. Yoo

Dissecting the Akt/Mammalian Target of Rapamycin Signaling Network: Emerging Results from the Head and Neck Cancer Tissue Array Initiative

Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. Conclusions: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.

Prognostic factors in major salivary gland cancer

Objective To identify features of major salivary gland cancers that are prognostic for disease‐free survival.

A multicenter phase II study of tgDCC-E1A for the intratumoral treatment of patients with recurrent head and neck squamous cell carcinoma.

The anti‐cancer gene, E1A, can be complexed to a lipid carrier, DC‐Cholesterol:DOPE, to form tgDCC‐E1A, which can be injected directly into tumors.

Autoantibody Approach for Serum-Based Detection of Head and Neck Cancer

Currently, no effective tool exists for screening or early diagnosis of head and neck squamous cell carcinoma (HNSCC). Here, we describe an approach for cancer detection based on analysis of patterns of serum immunoreactivity against a panel of biomarkers selected using microarray-based serologic profiling and specialized bioinformatics. We biopanned phage display libraries derived from three different HNSCC tissues to generate 5,133 selectively cloned tumor antigens. Based on their differential immunoreactivity on protein microarrays against serum immunoglobulins from 39 cancer and 41 control patients, we reduced the number of clones to 1,021. The performance of a neural network model (Multilayer Perceptron) for cancer classification on a data set of 80 HNSCC and 78 control samples was assessed using 10-fold cross-validation repeated 100 times. A panel of 130 clones was found to be adequate for building a classifier with sufficient sensitivity and specificity. Using these 130 markers on a completely new and independent set of 80 samples, an accuracy of 84.9% with sensitivity of 79.8% and specificity of 90.1% was achieved. Similar performance was achieved by reshuffling of the data set and by using other classification models. The performance of this classification approach represents a significant improvement over current diagnostic accuracy (sensitivity of 37% to 46% and specificity of 24%) in the primary care setting. The results shown here are promising and show the potential use of this approach toward eventual development of diagnostic assay with sufficient sensitivity and specificity suitable for detection of early-stage HNSCC in high-risk populations. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2396–405)

Biomarkers Predict p53 Gene Therapy Efficacy in Recurrent Squamous Cell Carcinoma of the Head and Neck

Purpose: Most recurrent squamous cell carcinomas of the head and neck have a dysfunctional p53 tumor suppressor pathway contributing to treatment resistance. We hypothesized that tumor p53 biomarkers may predict the efficacy of normal p53 delivered by gene therapy in these patients. Experimental Design: Tumor p53 biomarkers were evaluated in 116 patients, including 29 treated with methotrexate in a phase III randomized controlled trial. Profiles favorable for p53 gene therapy efficacy were hypothesized to have either normal p53 gene sequences or low-level p53 protein expression, whereas unfavorable p53 inhibitor profiles were predicted to have high-level expression of mutated p53 that can inhibit normal p53 protein function. Results: A statistically significant increase in tumor responses was observed for patients with favorable p53 efficacy profiles compared with those with unfavorable p53 inhibitor profiles [phase I/II trials: favorable (34 of 46, 74%) versus unfavorable (1 of 5, 20%), P = 0.0290; phase III trial: favorable (17 of 24, 71%) versus unfavorable (2 of 11, 18%), P = 0.0088]. In the phase III trial, there was statistically significant increased time to progression (TTP) and survival following p53 gene therapy in patients with favorable p53 profiles compared with unfavorable p53 inhibitor profiles (median TTP, 2.7 months versus 1.4 months, P = 0.0121; median survival, 7.2 months versus 2.7 months, P < 0.0001). In contrast, the biomarker profiles predictive of p53 gene therapy efficacy did not predict methotrexate response, TTP, or survival outcomes. Conclusions: These results indicate that tumor p53 biomarker profiles may predict p53 gene therapy efficacy in recurrent squamous cell carcinoma of the head and neck. (Clin Cancer Res 2009;15(24):7719–25)

Craniocervical Necrotizing Fasciitis: An 11-Year Experience

OBJECTIVE: We review our experience and present our approach to treating craniocervical necrotizing fasciitis (CCNF). STUDY DESIGN: All cases of CCNF treated at Wayne State University/Detroit Receiving Hospital from January 1989 to April 2000 were reviewed. Patients were analyzed for source and extent of infection, microbiology, co-morbidities, antimicrobial therapy, hospital days, surgical interventions, complications, and outcomes. RESULTS: A review of 250 charts identified 10 cases that met the study criteria. Five cases (50%) had spread of infection into the thorax, with only 1 (10%) fatality. An average of 24 hospital days (7 to 45), 14 ICU days (6 to 21), and 3 surgical procedures (1 to 6) per patient was required. CONCLUSION: Aggressive wound care, broad-spectrum antibiotics, and multiple surgical interventions resulted in a 90% (9/10) overall survival and 80% (4/5) survival for those with thoracic extension. SIGNIFICANCE: This is the largest single institution report of CCNF with thoracic extension identified to date.

Drug-Induced Sleep Endoscopy vs Awake Müller’s Maneuver in the Diagnosis of Severe Upper Airway Obstruction

Objective To compare fiber-optic nasal endoscopy with Müller’s maneuver (FNMM) against drug-induced sleep endoscopy (DISE) in diagnosing the presence of severe level-specific upper airway collapse in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). Study Design Case series with chart review. Setting Tertiary care academic center. Subjects and Methods Medical records of all adult patients undergoing diagnostic DISE as part of their surgical evaluation were reviewed. Patients were included if they had undergone FNMM and had documented Friedman tongue position and tonsillar grade prior to DISE. Airway obstruction on both endoscopic procedures was described according to airway level and severity. Severe airway obstruction was defined as >75% collapse on endoscopy. Results Fifty-three patients were included in this study. Fiber-optic nasal endoscopy with Müller’s maneuver and DISE did not differ significantly regarding the presence of severe retropalatal airway collapse. There was a statistically significant difference in the incidence of severe retrolingual collapse identified via DISE (84.9% [45/53]) compared with FNMM (35.8% [19/53]; P < .0001). This discrepancy between FNMM and DISE findings was statistically significant in individuals with Friedman I and II tongue positions (FNMM = 16.7%, DISE = 88.9%, P < .0001) and individuals with Friedman III tongue position (FNMM = 31.8%, DISE = 81.8%, P = .002). Patients with Friedman IV showed no significant difference (P = .65) between FNMM (69.2%) and DISE (84.6%). Conclusion This study shows a significant difference between FNMM and DISE in the identification of severe retrolingual collapse. Since the effectiveness of surgical interventions depends largely on the accurate preoperative identification of the site of obstruction, further scrutiny of each diagnostic endoscopic technique is warranted.

Lateral oropharyngeal wall and supraglottic airway collapse associated with failure in sleep apnea surgery.

To identify patterns of airway collapse during preoperative drug‐induced sleep endoscopy (DISE) as predictors of surgical failure following multilevel airway surgery for patients with obstructive sleep apnea‐hypopnea syndrome (OSAHS).

Assessment of Carotid Artery Invasion in Patients With Head and Neck Cancer

Purpose Define radiological and histological features in which patients with head and neck cancer would benefit from a carotid artery resection. Resection of the carotid artery has been advocated for local control of advanced squamous cell carcinoma of the head and neck. To provide appropriate preoperative counseling and optimize the utilization of resources, the criteria for patient selection has to be defined.

Transoral robotic surgery for treatment of obstructive sleep apnea‐hypopnea syndrome

To evaluate the efficacy of base of tongue (BOT) resection via transoral robotic surgery (TORS) in the treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS).