Otolaryngologists
22 years of experience
Video profile
Accepting new patients
Northeast Ann Arbor
Va Ann Arbor Healthcare System
2215 Fuller Rd
Ann Arbor, MI 48105
734-769-7100
Locations and availability (3)

Education ?

Medical School
Dalhousie University Faculty Of Medicine (1988)
Foreign school

Awards & Distinctions ?

Associations
American Academy of Otolaryngology: Head and Neck Surgery
American Head and Neck Society
American Board of Otolaryngology

Affiliations ?

Dr. Prince is affiliated with 3 hospitals.

Hospital Affilations

Score

Rankings

  • University of Michigan Hospitals & Health Centers
    Otolaryngology
    1500 E Medical Center Dr, Ann Arbor, MI 48109
    • Currently 4 of 4 crosses
    Top 25%
  • Ann Arbor Veterans Affairs Medical Center
    2215 Fuller Rd, Ann Arbor, MI 48105
  • University of Michigan Health System
  • Publications & Research

    Dr. Prince has contributed to 49 publications.
    Title Genome-wide Methylation and Expression Differences in Hpv(+) and Hpv(-) Squamous Cell Carcinoma Cell Lines Are Consistent with Divergent Mechanisms of Carcinogenesis.
    Date October 2011
    Journal Epigenetics : Official Journal of the Dna Methylation Society
    Excerpt

    Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous cell carcinomas (HNSCC) have distinct risk profiles and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as a mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(-) tumors is unknown. To investigate the epigenetic regulation of gene expression in HPV-induced and carcinogen-induced cancers, we examined genome-wide DNA methylation and gene expression in HPV(+) and HPV(-) SCC cell lines. We used two platforms: the Illumina Infinium Methylation BeadArray and tiling arrays, and confirmed illustrative examples with pyrosequencing and quantitative PCR. These analyses indicate that HPV(+) cell lines have higher DNA methylation in genic and LINE-1 regions than HPV(-) cell lines. Differentially methylated loci between HPV(+) and HPV(-) cell lines significantly correlated with HPV-typed HNSCC primary tumor DNA methylation levels. Novel findings include higher promoter methylation of polycomb repressive complex 2 target genes in HPV(+) cells compared to HPV(-) cells and increased expression of DNMT3A in HPV(+) cells. Additionally, CDKN2A and KRT8 were identified as interaction hubs among genes with higher methylation and lower expression in HPV(-) cells. Conversely, RUNX2, IRS-1 and CCNA1 were major hubs with higher methylation and lower expression in HPV(+) cells. Distinct HPV(+) and HPV(-) epigenetic profiles should provide clues to novel targets for development of individualized therapeutic strategies.

    Title End-of-life Care Among Head and Neck Cancer Patients.
    Date August 2011
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    This study is designed to (1) determine the perceived quality of care received by patients with head and neck cancer at the end of their lives, in order to (2) better anticipate and improve upon the experiences of future patients.

    Title Endothelial Cell-initiated Signaling Promotes the Survival and Self-renewal of Cancer Stem Cells.
    Date February 2011
    Journal Cancer Research
    Excerpt

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used aldehyde dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin-) led to tumors in 13 (out of 15) mice, whereas 10,000 noncancer stem cells (ALDH-CD44-Lin-) resulted in 2 tumors in 15 mice. These data demonstrated that ALDH and CD44 select a subpopulation of cells that are highly tumorigenic. The ability to self-renew was confirmed by the observation that ALDH+CD44+Lin- cells sorted from human HNSCC formed more spheroids (orospheres) in 3-D agarose matrices or ultra-low attachment plates than controls and were serially passaged in vivo. We observed that approximately 80% of the CSC were located in close proximity (within 100-μm radius) of blood vessels in human tumors, suggesting the existence of perivascular niches in HNSCC. In vitro studies demonstrated that endothelial cell-secreted factors promoted self-renewal of CSC, as demonstrated by the upregulation of Bmi-1 expression and the increase in the number of orospheres as compared with controls. Notably, selective ablation of tumor-associated endothelial cells stably transduced with a caspase-based artificial death switch (iCaspase-9) caused a marked reduction in the fraction of CSC in xenograft tumors. Collectively, these findings indicate that endothelial cell-initiated signaling can enhance the survival and self-renewal of head and neck CSC.

    Title Single-marker Identification of Head and Neck Squamous Cell Carcinoma Cancer Stem Cells with Aldehyde Dehydrogenase.
    Date December 2010
    Journal Head & Neck
    Excerpt

    In accord with the cancer stem cell (CSC) theory, only a small subset of cancer cells are capable of forming tumors. We previously reported that CD44 isolates tumorigenic cells from head and neck squamous cell cancer (HNSCC). Recent studies indicate that aldehyde dehydrogenase (ALDH) activity may represent a more specific marker of CSCs.

    Title Chemotherapy Alone for Organ Preservation in Advanced Laryngeal Cancer.
    Date December 2010
    Journal Head & Neck
    Excerpt

    For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy.

    Title Thoracodorsal Artery Scapular Tip Autogenous Transplant: Vascularized Bone with a Long Pedicle and Flexible Soft Tissue.
    Date November 2010
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    To demonstrate that the 3 reconstructive advantages of the thoracodorsal artery scapular tip transplant (Tdast), a long pedicle, independently mobile tissue components, and the 3-dimensional nature of the scapular tip, will improve the quality and success of complex reconstructions by avoiding vein grafting, preventing the need for 2 separate transplants, and facilitating bony inset.

    Title Intensity-modulated Chemoradiotherapy Aiming to Reduce Dysphagia in Patients with Oropharyngeal Cancer: Clinical and Functional Results.
    Date July 2010
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures to reduce post-therapy dysphagia.

    Title Hpv-positive/p16-positive/ebv-negative Nasopharyngeal Carcinoma in White North Americans.
    Date July 2010
    Journal Head & Neck
    Excerpt

    Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and Epstein-Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, and EBV status was examined in current University of Michigan patients with NPC.

    Title Tobacco Use in Human Papillomavirus-positive Advanced Oropharynx Cancer Patients Related to Increased Risk of Distant Metastases and Tumor Recurrence.
    Date April 2010
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    The goal of this study was to examine the effect of tobacco use on disease recurrence (local/regional recurrence, distant metastasis, or second primary) among patients with human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP) following a complete response to chemoradiation therapy.

    Title Oropharyngoplasty with Template-based Reconstruction of Oropharynx Defects.
    Date October 2009
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    To determine if oropharyngoplasty using a Gehanno technique of superior constrictor velopharyngoplasty, base of tongue mounding, and primary hypopharyngeal closure in combination with template-based revascularized free tissue transfer is effective for reconstruction of the oropharyngeal defect.

    Title Chemoselection As a Strategy for Organ Preservation in Patients with T4 Laryngeal Squamous Cell Carcinoma with Cartilage Invasion.
    Date August 2009
    Journal The Laryngoscope
    Excerpt

    High rates of overall survival (OS) and laryngeal preservation were achieved in two sequential phase II clinical trials in patients with stage III/IV laryngeal squamous cell carcinoma (SCC). Patients were treated with chemoradiation after a >50% primary tumor response to one cycle of neoadjuvant chemotherapy (IC). We analyzed outcomes for T4 patients with cartilage invasion from both studies.

    Title The Pattern of Failure After Reirradiation of Recurrent Squamous Cell Head and Neck Cancer: Implications for Defining the Targets.
    Date August 2009
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    Reirradiation (re-RT) of recurrent head and neck cancer (HNC) may achieve long-term disease control in some patients, at the expense of high rates of late sequelae. Limiting the re-RT targets to the recurrent gross tumor volume (rGTV) would reduce the volumes of reirradiated tissues; however, its effect on tumor recurrence pattern is unknown.

    Title Early Prediction of Outcome in Advanced Head-and-neck Cancer Based on Tumor Blood Volume Alterations During Therapy: a Prospective Study.
    Date December 2008
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To assess whether alterations in tumor blood volume (BV) and blood flow (BF) during the early course of chemo-radiotherapy (chemo-RT) for head-and-neck cancer (HNC) predict treatment outcome. METHODS AND MATERIALS: Fourteen patients receiving concomitant chemo-RT for nonresectable, locally advanced HNC underwent dynamic contrast-enhanced (DCE) MRI scans before therapy and 2 weeks after initiation of chemo-RT. The BV and BF were quantified from DCE MRI. Preradiotherapy BV and BF, as well as their changes during RT, were evaluated separately in the primary gross tumor volume (GTV) and nodal GTV for association with outcomes. RESULTS: At a median follow-up of 10 months (range, 5-27 months), 9 patients had local-regional controlled disease. One patient had regional failure, 3 had local failures, and 1 had local-regional failure. Reduction in tumor volume after 2 weeks of chemo-RT did not predict for local control. In contrast, the BV in the primary GTV after 2 weeks of chemo-RT was increased significantly in the local control patients compared with the local failure patients (p < 0.03). CONCLUSIONS: Our data suggest that an increase in available primary tumor blood for oxygen extraction during the early course of RT is associated with local control, thus yielding a predictor with potential to modify treatment. These findings require validation in larger studies.

    Title Lateral Oromandibular Defect: when is It Appropriate to Use a Bridging Reconstruction Plate Combined with a Soft Tissue Revascularized Flap?
    Date October 2008
    Journal Head & Neck
    Excerpt

    BACKGROUND: A quasi-experimental retrospective study was undertaken to evaluate a new concept of free tissue volume restoration combined with bridging reconstruction plate (compartment approach) to reduce plate-related complication rates. METHODS: We evaluated 40 patients with large lateral mandible defects and associated complex soft tissue defects reconstructed with a revascularized soft tissue flap and titanium hollow screw reconstruction plates. A case-control comparison was performed based on reconstruction type: restoration of soft tissue defect (conventional approach-group 1) versus over-reconstruction of soft tissue defect (compartment approach-group 2). RESULTS: Plate exposure rate was 6 of 16 (38%) in group 1 versus 2 of 24 (8%) in group 2, and the difference was statistically significant (p = .04). The mean time to exposure was 10 months. Plate fracture rate was 6 of 23 (26.1%) in dentulous patients versus 1 of 17 (5.9%) in edentulous patients. Gastrostomy tube dependence was 6 of 16 (38%) in group 1 versus 6 of 24 (25%) in group 2. CONCLUSION: The "compartment approach" reduces plate exposure rate and gastrostomy tube dependence. Revascularized osseocutaneous reconstruction is still required in dentulous patients.

    Title Rectangle Tongue Template for Reconstruction of the Hemiglossectomy Defect.
    Date October 2008
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To determine if a rectangular template free tissue transfer is effective for the reconstruction of the hemiglossectomy defect. DESIGN: Prospective case series. SETTING: Tertiary care academic medical center. PATIENTS: A total of 13 patients (male to female ratio, 8:5; mean age, 55 years) presenting with squamous cell carcinoma of the oral tongue from May 2000 to December 2002. INTERVENTIONS: Of the 13 patients, 7 received postoperative radiotherapy and 2 received prior radiotherapy. The radial forearm was the donor site in 11 patients and the lateral arm and anterolateral thigh in 1 patient each. The mean flap area was 50 cm(2) (range, 24-80 cm(2)). MAIN OUTCOME MEASURES: Major and minor complications, speech and swallowing assessment, oral cavity obliteration, premaxillary contact, tongue elevation, and tongue protrusion. RESULTS: There were no major complications, and 2 of the 13 patients experienced minor complications. Of the 13 patients, 12 achieved the goals of oral cavity obliteration and premaxillary contact and resumed solid oral intake. One patient remained G-tube dependent owing to toxic effects from previous chemoradiation treatment. The mean tongue tip protrusion was 0.7 cm (range, 0-1.7 cm), and the mean elevation was 1.7 cm (range, 1-3 cm). Patients with protrusion greater than 0.8 cm had better swallowing scores for "range of solids" (5.8 of 6 vs 3.9 of 6; P = .045) and "eating in public" (4.6 of 5 vs 3.5 of 5; P = .10). The average patient resumed a full range of liquid and solid intake with minimal restrictions and believed that their speech was mostly understandable with occasional repetition. CONCLUSIONS: The template-based rectangle tongue flap effectively restored speech and swallowing function in this group of patients. Tongue protrusion greater than 0.8 cm is associated with better swallowing results.

    Title Improved Outcomes in Patients with Head and Neck Cancer Using a Standardized Care Protocol for Postoperative Alcohol Withdrawal.
    Date August 2008
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To show clinical benefit in the main outcome measures by the use of a standardized protocol for identification, characterization, and treatment of alcohol withdrawal syndrome (AWS) in postoperative patients with head and neck cancer. DESIGN: Prospective cohort study with a retrospective cohort control. SETTING: Tertiary care university. PATIENTS: A total of 26 consecutive postoperative patients with AWS were selected from among 652 patients with head and neck cancer to be enrolled in the protocol from March 2003 through March 2005. Controls consisted of 14 of 981 consecutive patients with AWS from March 2000 through December 2002. INTERVENTION: Application of a standardized care protocol. MAIN OUTCOME MEASURES: Sensitivity and specificity of preoperative screening for AWS risk, predictability of outcomes, length of stay, transfers to the intensive care unit (ICU), AWS symptoms, postoperative morbidity and mortality, doses of pharmacotherapy required, and charges. RESULTS: Protocol patients demonstrated significantly fewer AWS-related ICU transfers and less delirium and violence than preprotocol patients. Mortality, wound complications, hospital charges, and doses of benzodiazepines, clonidine, and haloperidol were not significantly different between these 2 groups. Preoperative medical history correlated poorly with AWS outcomes. Screening was 87.5% sensitive and 99.7% specific. Late enrollees to the protocol (false-negative screening results) showed many significantly worse outcomes than immediate enrollees. CONCLUSION: Use of the standardized AWS symptom-triggered protocol decreased delirium, violence, and AWS-related ICU transfers without significantly increasing hospital charges.

    Title Egfr, P16, Hpv Titer, Bcl-xl and P53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal Cancer.
    Date August 2008
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. PATIENTS AND METHODS: Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status. RESULTS: EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (rho(EGFR) = 0.008; rho(HPV) = 0.03) and DSS (rho(EGFR) = 0.01; rho(HPV) = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002). CONCLUSION: Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.

    Title Chemoselection As a Strategy for Organ Preservation in Advanced Oropharynx Cancer: Response and Survival Positively Associated with Hpv16 Copy Number.
    Date August 2008
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. PATIENTS AND METHODS: Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. RESULTS: Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). CONCLUSION: Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

    Title Rap1gap Promotes Invasion Via Induction of Matrix Metalloproteinase 9 Secretion, Which is Associated with Poor Survival in Low N-stage Squamous Cell Carcinoma.
    Date June 2008
    Journal Cancer Research
    Excerpt

    The objective of the current study was to investigate the effects of Rap1GAP on invasion and progression of head and neck squamous cell carcinoma (SCC) and the role of matrix metalloproteinase (MMP) 9 and MMP2 in this process. Rap1GAP functions by switching off Rap1, the Ras-like protein that has been associated with carcinogenesis. Previous findings suggest that Rap1GAP acts as a tumor suppressor protein in SCC by delaying the G(1)-S transition of the cell cycle. However, cells transfected with Rap1GAP exhibit a more invasive phenotype than corresponding vector-transfected control cells. MMP2 and MMP9 are enzymes that mediate SCC invasion via degradation of the extracellular matrix. Using SCC cells transfected with empty vector or Rap1GAP, cell invasion and MMP secretion were determined by Matrigel assays and gelatin zymography, respectively. Rap1GAP up-regulated transcription and secretion of MMP2 and MMP9, as assayed by quantitative reverse transcription-PCR and zymography. Furthermore, chemical and RNA interference blockade of MMP2/MMP9 inhibited invasion by Rap1GAP-transfected cells. Immunohistochemical staining of a human oropharyngeal SCC tissue microarray showed that Rap1GAP and MMP9 expression and staining intensity are correlated (P < 0.0001) and that, in early N-stage lesions of SCC, high MMP9 is prognostic of poor disease-specific survival (P < 0.05). Furthermore, Rap1GAP staining is correlated with MMP2 (P < 0.03). MMP2 in combination with N stage has a prognostic effect on time to indication of surgery at primary site. MMP2 intensity is also positively correlated with T stage (P < 0.015). In conclusion, Rap1GAP inhibits tumor growth but induces MMP2- and MMP9-mediated SCC invasion and tumor progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive SCCs.

    Title Cancer Stem Cells in Head and Neck Squamous Cell Cancer.
    Date June 2008
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    Appropriate treatment of head and neck squamous cell cancer (HNSCC) remains one of the most difficult challenges in head and neck oncology. Overall survival of patients with HNSCC remains at approximately 50% at 5 years. Surgical therapy can be mutilating and often has significant effects on swallowing, speech, and physical appearance. The addition of chemotherapy to radiation treatment has shown efficacy in organ preservation in some sites in the head and neck, but has resulted in limited improvement in survival rates. HNSCC resistance to chemotherapy has limited the usefulness of chemotherapy in the treatment of this disease. We have recently demonstrated that human head and neck squamous cell cancers contain a tumorigenic, so-called cancer stem cell, subpopulation of cells that can self-renew and produce differentiated cells that form the bulk of the tumor. These tumorigenic HNSCC cells have a distinct phenotype and can be identified by a surface marker. Current treatment for HNSCC regimens may selectively kill the differentiated cancer cells, producing tumor regression while sparing the cancer stem cells, leading to tumor regrowth and relapse. It is important for us to understand why HNSCC does not respond to chemotherapy and to identify new targeted treatments that can overcome resistance and improve patient outcomes. Further study of HNSCC stem cells will increase our knowledge of this devastating disease and allow us to develop novel treatments.

    Title Expression of P53 and Bcl-xl As Predictive Markers for Larynx Preservation in Advanced Laryngeal Cancer.
    Date June 2008
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To assess tumor markers in advanced laryngeal cancer. DESIGN: Marker expression and clinical outcome. PATIENTS: Pretreatment tumor biopsy specimens were analyzed from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Study. MAIN OUTCOME MEASURES: Expression of p53 (OMIM TP53) and Bcl-xL (OMIM 600039) in pretreatment biopsy specimens was assessed for correlation with chemotherapy response, laryngeal preservation, and survival. RESULTS: Higher rates of larynx preservation were observed in patients whose tumors expressed p53 vs those that did not (80% [36 of 45 patients] vs 59% [24 of 41 patients], P =.03). Higher rates of larynx preservation were also observed in patients whose tumors expressed low levels of Bcl-xL vs high levels of Bcl-xL (90% [18 of 20 patients] vs 60% [30 of 50 patients], P =.02). Patients were categorized into 3 risk groups (low, intermediate, and high) based on their tumor p53 and Bcl-xL expression status. Patients whose tumors had the high-risk biomarker profile (low p53 expression and high Bcl-xL expression) were less likely to preserve their larynx than patients whose tumors had the intermediate-risk biomarker profile (high p53 expression and low or high Bcl-xL expression) or the low-risk biomarker profile (low p53 expression and low Bcl-xL expression). The larynx preservation rates were 100% (10 of 10 patients), 77% (26 of 34 patients), and 54% (7 of 13 patients) for the low-risk, intermediate-risk, and high-risk groups, respectively (P =.04, Fisher exact test). CONCLUSION: Tumor expression of p53 and Bcl-xL is a strong predictor of successful larynx preservation in patients treated with induction chemotherapy and followed by radiation therapy in responding tumors.

    Title Targeting Apoptosis to Overcome Cisplatin Resistance: a Translational Study in Head and Neck Cancer.
    Date November 2007
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: Cisplatin resistance remains a barrier to organ-sparing and survival of patients with advanced head and neck squamous cell carcinoma (HNSCC). Targeted therapies to overcome cisplatin-resistant HNSCC are being developed. METHODS AND MATERIALS: Cisplatin-sensitive parental HNSCC cell lines and cisplatin-resistant progeny were studied. Pretreatment HNSCC biopsies were used to construct tissue microarrays which were stained for p53 and Bcl-xL. RESULTS: HNSCC cell lines selected for cisplatin resistance had wild-type p53 and high levels of Bcl-xL. Expression of wild-type p53 in cell lines with low Bcl-xL enhanced cisplatin sensitivity. Expression of both Bcl-xL and wild-type p53 caused tumor cells to become cisplatin resistant. Patients whose tumors expressed low levels of p53 and Bcl-xL enjoyed the best organ preservation and disease-free survival whereas patients whose tumors expressed low levels of p53 and high levels of Bcl-xL had the worst outcome. Novel agents that inhibit Bcl-xL or activate p53 function may target cisplatin-resistant HNSCC. CONCLUSION: Cisplatin resistance in HNSCC is mediated, at least in part, by high Bcl-xL and functional p53.

    Title Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated with Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking.
    Date November 2007
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.

    Title Successful Multimodal Treatment of a Carcinosarcoma of the Masticator Space.
    Date September 2007
    Journal The Journal of Otolaryngology
    Title An Unusual Thyroglossal Duct Cyst Infection with Coccidioidomycosis.
    Date July 2007
    Journal The Journal of Otolaryngology
    Title Tissue-preserving Approach to Extracting Dna from Paraffin-embedded Specimens Using Tissue Microarray Technology.
    Date June 2007
    Journal Head & Neck
    Excerpt

    BACKGROUND: DNA extracted from tumor cells or normal cells contained in formalin-fixed, paraffin-embedded tissues is widely used in many laboratories. The 2 most common procedures to isolate cells for DNA extraction from paraffin-embedded tissues are scalpel microdissection and laser capture microdissection. A new tissue- and time-conserving method for rapid DNA isolation from small cores taken from paraffin-embedded tissue blocks is described in this report. METHODS: DNA was extracted from small tissue cores collected from paraffin-embedded tissue blocks at the time of tissue microarray construction. The quality and quantity of the DNA extracted was compared to DNA collected by scalpel microdissection. DNA collected from tissue cores was used in polymerase chain reaction (PCR) and loss of heterozygosity (LOH) analysis. RESULTS: The quality and quantity of DNA obtained using tissue cores was comparable to DNA obtained by traditional methods. The tissue core method of DNA extraction preserves the tissue blocks from which the cores are extracted for future use. Adequate quantities of DNA can be successfully extracted from small segments of tissue cores and used for PCR. DNA isolated by tissue microdissection and the tissue core method were comparable when used to assess allelic heterozygosity on chromosome arm 18q. CONCLUSION: The tissue core method of DNA isolation is reliable, tissue conserving, and time effective. Tissue cores for DNA extraction can be harvested at the same time as tissue microarray construction. The technique has the advantage of preserving the original tissue blocks for additional study as only tiny cores are removed.

    Title Prevention of Wound Complications Following Salvage Laryngectomy Using Free Vascularized Tissue.
    Date June 2007
    Journal Head & Neck
    Excerpt

    BACKGROUND: Total laryngectomy following radiation therapy or concurrent chemoradiation therapy is associated with unacceptably high complication rates because of wound healing difficulties. With an ever increasing reliance on organ preservation protocols as primary treatment for advanced laryngeal cancer, the surgeon must develop techniques to minimize postoperative complications in salvage laryngectomy surgery. We have developed an approach using free tissue transfer in an effort to improve tissue vascularity, reinforce the pharyngeal suture line, and minimize complications in this difficult patient population. The purpose of this study was to outline our technique and determine the effectiveness of this new approach. METHODS: We conducted a retrospective review of a prospective cohort and compared it with a historical group (surgical patients of Radiation Therapy Oncology Group (RTOG)-91-11 trial). Eligibility criteria for this study included patients undergoing salvage total laryngectomy following failed attempts at organ preservation with either high-dose radiotherapy or concurrent chemo/radiation therapy regimen. Patients were excluded if the surgical defect required a skin paddle for pharyngeal closure. The prospective cohort consisted of 14 consecutive patients (10 males, 4 females; mean age, 58 years) who underwent free tissue reinforcement of the pharyngeal suture line following total laryngectomy. The historical comparison group consisted of 27 patients in the concomitant chemoradiotherapy arm of the RTOG-91-11 trial who met the same eligibility criteria (26 males, 1 female; mean age, 57 years) but did not undergo free tissue transfer or other form of suture line reinforcement. Minimum follow-up in both groups was 12 months. RESULTS: The overall pharyngocutaneous fistula rate was similar between groups-4/14 (29%) in the flap group, compared with 8/27 (30%) in the RTOG-91-11 group. There were no major wound complications in the flap group, compared with 4 (4/27, 14.8%) in the RTOG-91-11 group. There were no major fistulas in the flap group, compared with 3/27 (11.1%) in the RTOG-91-11 group. The rate of pharyngeal stricture requiring dilation was 6/14 (42%) in the flap group, compared with 7/27 (25.9%) in the RTOG-91-11 group. In our patients, the rate of tracheoesophageal speech was 14/14 (100%), and complete oral intake was achieved in 13/14 (93%) patients. Voice-Related Quality of Life Measure (V-RQOL) and Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) scores suggest that speech and swallowing functions are reasonable following free flap reinforcement. CONCLUSIONS: Free vascularized tissue reinforcement of primary pharyngeal closure in salvage laryngectomy following failed organ preservation is effective in preventing major wound complications but did not reduce the overall fistula rate. Fistulas that developed following this technique were relatively small, did not result in exposed major vessels, and were effectively treated with outpatient wound care rather than readmission to the hospital or return to operating room. Speech and swallowing results following this technique were comparable to those following total laryngectomy alone.

    Title Identification of a Subpopulation of Cells with Cancer Stem Cell Properties in Head and Neck Squamous Cell Carcinoma.
    Date February 2007
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC) contains a heterogeneous population of cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We show that a minority population of CD44(+) cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. The tumors that arose from purified CD44(+) cells reproduced the original tumor heterogeneity and could be serially passaged, thus demonstrating the two defining properties of stem cells: ability to self-renew and to differentiate. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to play a role in self-renewal in other stem cell types and to be involved in tumorigenesis. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis.

    Title Variables Associated with Feeding Tube Placement in Head and Neck Cancer.
    Date July 2006
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To identify clinical factors associated with enteral feeding tube placement in a head and neck cancer population. DESIGN: A self-administered survey was given to patients being treated for head and neck cancer while they were waiting to be seen in 1 of 4 otolaryngology clinics. The post hoc analysis presented here combines survey and chart review data to determine clinical and demographic variables associated with feeding tube placement. SETTING: Four otolaryngology clinics. PATIENTS: Otolaryngology clinic patients being treated for head and neck cancer. MAIN OUTCOME MEASURE: Enteral feeding tube placement. RESULTS: Of the 724 patients eligible for this study, 14% (n = 98) required enteral feeding tube placement. Multivariate analysis found the following variables to be independently associated with feeding tube placement: oropharynx/hypopharynx tumor site (odds ratio [OR], 2.4; P = .01), tumor stage III/IV (OR, 2.1; P = .03), flap reconstruction (OR, 2.2; P = .004), current tracheotomy (OR, 8.0; P<.001), chemotherapy (OR, 2.6; P<.001), and increased age (OR, 1.3; P = .02). In addition, there was a curvilinear relationship between time since treatment and feeding tube placement, with about 30% having a feeding tube at 1 month posttreatment, tapering down during the first 3 years to about 8% and leveling off thereafter. CONCLUSIONS: Identification of factors associated with an increased risk of feeding tube placement may allow physicians to better counsel patients regarding the possibility of feeding tube placement during treatment. Since feeding tube placement has been linked to decreased quality of life in head and neck cancer, such counseling is an integral part of the clinical management of these patients.

    Title Familial Zenker's Diverticulum: Case Study and Historical Perspective.
    Date April 2006
    Journal The Journal of Otolaryngology
    Title Voice and Swallowing Outcomes of an Organ-preservation Trial for Advanced Laryngeal Cancer.
    Date January 2006
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    INTRODUCTION: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. SUBJECTS: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU 1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease. METHODS: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months. RESULTS: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09). CONCLUSIONS: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.

    Title Osseocutaneous Radial Forearm Free Tissue Transfer for Repair of Complex Midfacial Defects.
    Date July 2005
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To evaluate the resulting aesthetics, function, and donor site morbidity of the osseocutaneous radial forearm free flap (OCRFFF) used for midface reconstruction. DESIGN: Prospective case series and a retrospective review of results. PATIENTS: Ten patients from an academic practice who underwent reconstruction at the University of Michigan Hospitals between 1995 and 2001. INTERVENTIONS: All patients had maxillectomy defects in which the entire infraorbital rim was reconstructed with an OCRFFF. Of the 10 patients included in the study, 3 underwent a total maxillectomy with orbital exenteration, 4 had a total maxillectomy without orbital exenteration, and 3 had a limited maxillectomy that did not involve the palate. Patients with palatal defects underwent reconstruction with a prosthetic palatal obturator. MAIN OUTCOME MEASURES: Facial contour and aesthetic results, speech understandability, ability to eat solid foods, oronasal separation, socializing outside the home, and return-to-work status. Flap success, donor site morbidity, and orbital complications were also studied. RESULTS: Mean +/- SEM follow-up was 23.2 +/- 5.0 months. A modified Funk facial deformity scale was used, and 7 of the 10 patients had either no deformity or minimal deformity. The mean aesthetic score for these reconstructions was 2.1 +/- 0.3 on a scale of 1 to 4, with 1 representing no deformity and 4 representing a severe deformity. All patients returned to a solid diet and had understandable speech, although patients who had an orbital exenteration trended to poorer scores. All patients socialized either frequently or occasionally outside the home, and all patients not retired or disabled prior to surgery returned to work. CONCLUSION: The OCRFFF reconstruction of the infraorbital rim in patients with total maxillectomy defects and obturator of the palatal defect controls orbital complications and optimizes aesthetic outcome while achieving nearly normal palatal function.

    Title Radial Forearm Free Tissue Transfer Reduces Complications in Salvage Skull Base Surgery.
    Date March 2005
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: Patients who undergo skull base resection after prior surgery or radiation may be at high risk for complications when local flaps alone are used for reconstruction. To determine whether the complication rate could be reduced, fasciocutaneous free tissue transfer was used to reinforce the dural closure in patients who had prior skull base surgery or radiation. METHODS: This study is a case series of 20 patients (14 males, 6 females, aged 8-79 years of age with a mean of 47.7 years) from 1997 to 2001 who had prior skull base surgery or radiation, and underwent salvage skull base resection without large volume defects. All patients had a radial forearm free tissue transfer to reinforce the dural closure. Six patients had an osseous component to the forearm flap to provide vascularized bone to the orbital rim. RESULTS: The overall local complication rate was 35%. Three patients (15%) had major complications including 1 case of meningitis, 1 case of cerebrospinal fluid leak, and 1 case of a flap requiring venous salvage. There were no flap failures, 1 idiopathic median nerve palsy, and no pathologic radius bone fractures. CONCLUSION: Reconstruction with fasciocutaneous free tissue transfer for high-risk patients with low-volume dural defects following skull base resection can minimize the risk of major postoperative complications. EBM RATING: C.

    Title Restoration of the Orbital Aesthetic Subunit in Complex Midface Defects.
    Date December 2004
    Journal The Laryngoscope
    Excerpt

    OBJECTIVES/HYPOTHESIS: Although various options exist for restoration of the orbital defect in complex craniofacial resections, the aesthetic appearance and functional result of the orbit are optimized when the bony orbital architecture, orbital volume, and facial contour are specifically addressed. The study describes an approach using free tissue transfer for restoration of the native orbital aesthetic subunit. STUDY DESIGN: Retrospective case series. METHODS: Nineteen patients (male-to-female ratio, 14:5; mean age, 52 y [age range, 8-79 y]) in the study period between 1997 and 2001 had orbital defects that could be classified into one of the following categories: 1) orbital exenteration cavities only, 2) orbital exenteration cavities with resection of less than 30% of the bony orbital rim, or 3) radical orbital exenteration cavities with resection of overlying skin and bony malar eminence. Group 1 had reconstructions with fasciocutaneous forearm flaps; group 2, with osseocutaneous forearm flaps; and group 3, with osseocutaneous scapula flaps. RESULTS: Eighteen of 19 patients achieved a closed orbital reconstruction with restoration of the orbital aesthetic subunit. Among 16 patients with more than 4 months of follow-up, 10 patients had minimal or no resulting facial contour deformity and 8 patients engaged in social activities outside the home on a frequent basis. Five of the nine patients who were working before their surgery were able to return to work. CONCLUSION: Patients with complex midface defects involving the orbit can undergo free tissue transfer and have successful restoration of the native orbital aesthetic subunit without an orbital prosthesis.

    Title Disability in Patients with Head and Neck Cancer.
    Date July 2004
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    BACKGROUND: Patients with head and neck cancer often experience debilitating speech, eating, and respiratory problems as well as the psychological effects of loss of function and change in body image. These patients often become unemployed as a result of their disease process, which adds financial burden to their already stressful lives. Yet the specific factors associated with unemployment have not been systematically studied. METHODS: This multisite study used survey and chart data to determine the predictors of work-related disability. RESULTS: Of the 384 patients who were working prior to their diagnosis of head and neck cancer, 52% (n = 201) were disabled by their cancer treatment. Multivariate analysis demonstrated significant links between disability and chemotherapy (odds ratio [OR], 3.4; P <.001), neck dissection status (OR, 2.3; P =.01), pain scores (OR, 1.2; P =.01), and time since diagnosis (OR, 0.9; P =.04). CONCLUSIONS: More than half of the patients in this study were disabled by their head and neck cancer or treatment. Patients with head and neck cancer who have undergone chemotherapy or neck dissection or have high pain scores are at increased risk for disability from their cancer or their treatment. Efforts to prevent (if possible), better assess, and treat pain and other adverse effects of head and neck cancer treatments may also have the potential to reduce patient disability.

    Title Cartilaginous Tumours of the Larynx.
    Date May 2004
    Journal The Journal of Otolaryngology
    Excerpt

    Cartilaginous tumours of the larynx are rare. Chondrosarcomas represent the most common sarcoma involving this site. A series of seven patients with the diagnosis of chondrosarcoma of the larynx from the cancer registry at the University of Michigan Medical Center from 1975 to 1997 and one recent case from the Ann Arbor Department of Veterans Affairs Hospital were identified. One patient with a laryngeal chondroma was also included in the series. Pertinent clinical, pathologic, and therapeutic data were reviewed. In three of the nine patients, tumours involved the thyroid cartilage; the remainder, including the chondroma, arose from the cricoid cartilage. Four of the chondrosarcomas were histopathologic grade I, three were grade II, and one was grade III. Surgical treatment of the chondrosarcomas included five total laryngectomies, three laryngofissures with resection, and a partial cricoid resection. Six patients are alive without disease, including one patient who had direct spread to the thyroid gland and a peristomal recurrence that was excised. The patient with a grade III tumour developed pulmonary metastases 6 months after total laryngectomy and radiation therapy and died. One patient died of other causes. These findings confirm previous reports that chondrosarcomas are usually slow growing and demonstrate an indolent clinical course and that low-grade chondrosarcomas arising in the larynx may be excised with close surgical margins without compromising survival. This series suggests that local recurrence of low-grade lesions can be salvaged surgically, even after total laryngectomy, and that high-grade chondrosarcomas, although exceedingly rare, are much more aggressive neoplasms with a greater tendency to metastasize.

    Title Clinical Predictors of Quality of Life in Patients with Head and Neck Cancer.
    Date May 2004
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To identify clinical predictors of quality of life (QoL) in a head and neck cancer patient population. DESIGN, PATIENTS, AND SETTING: A convenience sample of 570 patients with upper aerodigestive tract cancers were surveyed at a tertiary care oncology clinic and Veterans Affairs otolaryngology clinic. INTERVENTIONS: A self-administered health survey was constructed to collect demographic, health, smoking, alcohol, depression symptom, and QoL information. Tumor site and tumor stage, clinical, and treatment data were abstracted from the patient medical records. MAIN OUTCOME MEASURES: Quality of life was assessed using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the Head and Neck QoL (HNQoL) instrument. RESULTS: Of the 570 eligible respondents, the presence of a feeding tube had the most negative impact on QoL, with significant decrements in 6 of the 8 SF-36 scales and all 4 HNQoL scales (P<.01). In descending order of severity, medical comorbid conditions, presence of a tracheotomy tube, chemotherapy, and neck dissection were also associated with significant (P<.05) decrements in QoL domains. Patients who took the survey more than 1 year after diagnosis had improved QoL in 7 of 12 domains. Hospital site, age, education level, sex, race, and marital status were also significant predictors of QoL. CONCLUSION: There are at least 13 demographic and clinical characteristics that are significant predictors of QoL in patients with head and neck cancer, which should be considered when treating patients and conducting QoL studies in the future.

    Title Reconstruction of Complex Parotidectomy Defects Using the Lateral Arm Free Tissue Transfer.
    Date October 2003
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVES: The study goal was to show that the lateral arm flap is a viable reconstructive option for complex parotidectomy defects.Study design and setting We studied a case series at a tertiary care medical center from March 1997 to March 2002. The lateral arm flap was used to reconstruct parotidectomy defects that included a composite resection of adjacent tissue in 30 patients. There were 19 men and 11 women (mean age, 62 years; mean follow-up, 19 months). The mean flap area was 114 cm(2), and the mean flap volume was 172 cm(3). The posterior cutaneous nerve of the forearm (PCNF) was used as a facial nerve cable graft in 14 patients. Facial disability outcomes were measured using the Facial Clinimetric Evaluation scale. RESULTS: The major and minor complication rates with use of this reconstructive approach were low: 16.7% (5 of 30) and 26.7% (8 of 30), respectively. Donor site morbidity was minimal, with no patient having a major donor site complication and 23.3% (7 of 30) having minor complications. Functional recovery of the facial nerve occurred in 6 of 8 evaluable patients who underwent facial nerve grafting using the PCNF. Controlling for degree of facial nerve paralysis, Facial Clinimetric Evaluation scale scores of our patients were not statistically different than those of a historic population with a facial paralysis and no surgical defect. CONCLUSIONS: The lateral arm free flap effectively restores facial appearance when used for reconstruction of complex parotidectomy defects. The PCNF, a nerve harvested with the lateral arm flap, can be used as a facial nerve cable graft with a high rate of success. SIGNIFICANCE: The lateral arm flap is successful as a single donor site for reconstructing facial contour and the facial nerve after major ablative defects in the parotid region.

    Title Dedifferentiated Liposarcoma of the Cheek: Case Report and Literature Review.
    Date November 2002
    Journal The Journal of Otolaryngology
    Title Ceruminous Adenocarcinoma: a Rare Tumour of the External Auditory Canal.
    Date May 2002
    Journal The Journal of Otolaryngology
    Title Procedure for Laryngotracheal Separation in the Goat: Development of a New Animal Model for Analysis of Craniofacial Growth.
    Date April 2001
    Journal Comparative Medicine
    Excerpt

    Most animal models used to study the process of postnatal craniofacial growth require direct manipulation of the craniofacial area, a growth period, then evaluation of the area. However, the scar tissue associated with direct manipulation of the craniofacial structures can produce growth abnormalities that are unrelated to the manipulation itself. To avoid this confounding variable in the study of craniofacial growth, we developed an animal model that involves laryngotracheal separation in a young animal. Our procedure completely separates the trachea from the upper aerodigestive tract and removes the site of scar tissue formation from the region of investigation. The tracheal stomas of the goats we describe were maintained for as long as 9 months. Unlike human patients, goats with laryngotracheal separation require laryngectomy tubes to prevent life-threatening stenosis of the tracheal stoma. Here we describe the operative procedure and post-operative care required for this new animal model.

    Title Optic, Olfactory, and Vestibular Dysmorphogenesis in the Homozygous Mouse Insertional Mutant Tg9257.
    Date December 1999
    Journal Journal of Craniofacial Genetics and Developmental Biology
    Excerpt

    The transgene insertional mutation 9257 on mouse chromosome 18 was originally identified by the circling behavior caused by vestibular abnormalities in heterozygous mutants. To characterize the homozygous phenotype, we generated F2 offspring from the cross (C57BL/6J-tg/+ x DBA/2J). Eye defects ranging in severity from microphthalmia to anophthalmia were observed in the tg/tg offspring. Dysmorphic development of the lens was evident as early as E10.5 in homozygous transgenic mice. Apparent agenesis of the lateral semicircular canal was evident at E14.5. Anomalies of nasomaxillary structures and olfactory neuroepithelium were present in heterozygous and homozygous transgenic mice. The 9257 mutation provides a model for analysis of the morphogenesis of these three neurosensory systems and their associated bony structures.

    Title Analysis of the Intranasal Distribution of Ointment.
    Date March 1998
    Journal The Journal of Otolaryngology
    Excerpt

    OBJECTIVE: The use of intranasal ointment sniffed into the nasal cavity is widely recommended as a method to lubricate the nose and to prevent drying and crusting of the nasal mucosa and secretions. This therapy is often prescribed to patients with problems with minor episodes of epistaxis, after nasal packing has been removed, and in patients complaining of excessive dryness or crusting within the nose. Various preparations have been used for this purpose. At our institution Polysporin ointment is one of the commonly used preparations. This study evaluated the distribution of Polysporin ointment within the nasal cavities of subjects with no symptoms related to the nasal cavity. CONCLUSIONS: The results of the study raise doubts about the effectiveness of this therapy.

    Title Nasopharyngeal Angiomyolipoma.
    Date March 1998
    Journal The Journal of Otolaryngology
    Title Effect of Upper-airway Passages on Craniofacial Growth in an Animal Model: a Pilot Study.
    Date December 1997
    Journal The Journal of Otolaryngology
    Excerpt

    OBJECTIVE: The process of postnatal growth and development of the face and skull is of major interest to otolaryngologists. Surgery is often considered as an option for the treatment of benign and malignant tumours, traumatic facial deformities, and congenital abnormalities of the head and neck in children and adolescents. The extent of surgery and the type of reconstruction is frequently influenced by concerns about the potential effect on future craniofacial growth. Surgery is also sometimes recommended as a method to influence facial growth as in tonsillectomy and adenoidectomy for 'adenoid facies syndrome.' There are a number of different theories concerning the factors that influence the growth of the face and cranium. None of these is universally accepted. The predominant theory is the functional matrix theory. This study was designed to evaluate the validity of this theory in an animal model. A new animal model had to be developed to perform the study. This pilot study was then conducted. METHOD: A laryngotracheal separation procedure was performed on juvenile goats. This effectively eliminated the use of the upper airway by the animals, thereby removing one of the major functional matrices from the model. The animals were allowed to grow. A control group was used, and comparisons were made between the two groups. RESULTS: The results of the study suggest that the functional matrix theory is not valid in this experimental model. CONCLUSIONS: Further research is required to confirm this finding. This would have important implications for our understanding of the biology of craniofacial growth and have clinical ramifications for otolaryngologists and other clinicians with an interest in the head and neck.

    Title Liposarcoma of the Retropharyngeal Space: Review of the Literature.
    Date June 1997
    Journal The Journal of Otolaryngology
    Title Skin Cancer of the Head and Neck with Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure.
    Date
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. METHODS AND MATERIALS: Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. RESULTS: Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. CONCLUSIONS: Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.

    Title High Sept9_v1 Expression Is Associated with Poor Clinical Outcomes in Head and Neck Squamous Cell Carcinoma.
    Date
    Journal Translational Oncology
    Excerpt

    The purpose of this work was to determine SEPT9_v1 expression levels in head and neck squamous cell carcinoma (HNSCC) and to analyze whether SEPT9_v1 expression is relevant to clinical outcomes. Recently, the SEPT9 isoform SEPT9_v1 has been implicated in oncogenesis, and methylation of the SEPT9 promoter region was reported in HNSCC. These findings led us to hypothesize that SEPT9_v1 could be differently expressed in HNSCC. To determine whether SEPT9_v1 is expressed in HNSCC, tissue microarray immunohistochemical analysis was performed using a SEPT9_v1-specific antibody. Tissue microarrays stained with a polyclonal SEPT9_v1-specific antibody was used to determine protein expression levels in HNSCC tissue samples, some with known clinical outcomes. This analysis showed that SEPT9_v1 is in fact highly expressed in HNSCC compared with normal epithelium, and high expression levels directly correlated with poor clinical outcomes. Specifically, a high SEPT9_v1 expression was associated with decreased disease-specific survival (P = .012), time to indication of surgery at primary site (P = .008), response to induction chemotherapy (P = .0002), and response to chemotherapy (P = .02), as well as advanced tumor stage (P = .012) and N stage (P = .0014). The expression of SEPT9_v1 was also strongly correlated with smoking status (P = .00094). SEPT9_v1 is highly expressed in HNSCC, and a high expression of SEPT9_v1 is associated with poor clinical outcomes. These data indicate that SEPT9_v1 warrants additional investigation as a potential biomarker for HNSCC.

    Title Metastatic Potential of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma.
    Date
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    to design in vitro and in vivo models of metastasis to study the behavior of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC).


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