Steven J Wang

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Scholarly Contributions

Chapters

• Clark, J., & Wang, S. J. (2016). Surgery for Malignant Neoplasms Metastatic to the Salivary Glands. In Salivary Gland Neoplasms. Switzerland.
• Heaton, C., & Wang, S. J. (2013). Lymph node procedures of the head and neck. In Merkel Cell Carcinoma. New York, NY: Springer Science.
• Wang, S. J., & Eisele, D. (2013). Facial nerve monitoring during parotidectomy. In Controversies in the Management of Salivary Gland Disease. Oxford, UK: Oxford University Press.

Journals/Publications

• Groysman, M., Yi, S. K., Robbins, J. R., Hsu, C. C., Julian, R., Bauman, J. E., Baker, A., Wang, S. J., & Bearelly, S. (2022). The impact of socioeconomic and geographic factors on access to transoral robotic/endoscopic surgery for early stage oropharyngeal malignancy. American journal of otolaryngology, 43(1), 103243.
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  To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC).
• Wang, S. J., Howe, C. L., Hamman, J., Borgstrom, M., Bearelly, S., & Baker, A. (2022). Impact of Close Margins in Head and Neck Mucosal Squamous Cell Carcinoma: A Systematic Review.. The Laryngoscope, 132(2), 307-321. doi:10.1002/lary.29690
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  The aim of the study is to investigate whether close surgical margins impact oncologic outcomes compared to clear or involved surgical margins. We hypothesize that close surgical margins portend worse outcomes compared with clear margins, but improved outcomes compared with involved margins..Systematic review..Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement standards, a systematic search was conducted for studies that reported oncologic outcomes following excision of primary mucosal head and neck squamous cell carcinoma (HNSCC). A meta-analysis was then performed, comparing local recurrence (LR), locoregional recurrence (LRR), and overall survival (OS) in patients with clear, close, and involved margins..Twenty-six studies met the inclusion criteria, totaling 8,435 patients. About 96% of our included cases involved the oral cavity, 2% involved the oropharynx, and 2% other. Also, 68% of cases were T1/T2 and 32% were T3/T4. On meta-analysis, clear margins were associated with lower incidence of 5-year LR relative risk (RR) 0.50, 95% confidence interval [CI] 0.38-0.65) and higher 5-year OS (RR 1.22, 1.11-1.35), when compared with close margins. Involved margins had higher incidence of 5-year LR (RR 1.75, 1.16-2.64), higher incidence of LRR at last follow-up (RR 1.66, 1.37-2.00), and no difference in 5-year OS (RR 0.82, 0.60-1.11), when compared with close margins..There is a stepwise improvement in oncologic outcomes as surgical margin categorically improves from involved to close to clear. Patients with close margins therefore may benefit from adjuvant therapy. Further research is required to investigate whether these findings are seen in non-oral cavity cases because they were underrepresented in this analysis. Laryngoscope, 132:307-321, 2022.
• Wang, S. J., Schmalbach, C. E., Ow, T. J., Choi, K. Y., O'Leary, M., Lin, A., Hughley, B. B., Emerick, K. S., Moore, B., Lee, N. Y., & Zandberg, D. P. (2022). American Head and Neck Society position statement on the use of PD ‐1 inhibitors for treatment of advanced cutaneous squamous cell carcinoma. Head & Neck, 45(1), 32-41. doi:10.1002/hed.27202
• Wang, S. J., & O'leary, M. A. (2021). Epidemiology and Prevention of Cutaneous Cancer.. Otolaryngologic clinics of North America, 54(2), 247-257. doi:10.1016/j.otc.2020.11.001
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  Cutaneous malignancy is becoming an increasing public health burden in terms of morbidity and cost, associated with changing environmental exposures and increased longevity of the general and the immunosuppressed population. Yet the understanding of the scope of this problem is hindered by lack of robust registries for nonmelanoma skin cancer. The risk factor responsible for most of these cancers, exposure to ultraviolet radiation, can be mitigated. However, greater consensus is necessary to enact effective prevention and screening programs. New developments, including identification of biomarkers and use of artificial intelligence, show promise for targeting screening efforts.
• Xu, M. J., Plonowska, K. A., Gurman, Z. R., Humphrey, A. K., Ha, P. K., Wang, S. J., El-Sayed, I. H., Heaton, C. M., George, J. R., Yom, S. S., Algazi, A. P., & Ryan, W. R. (2020). Treatment modality impact on quality of life for human papillomavirus-associated oropharynx cancer. The Laryngoscope, 130(2), E48-E56.
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  Compare treatment-related quality of life (QOL) impact for early-stage human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC) patients.
• Han, J. E., Yi, S. K., Wang, S., Erman, A., Bearelly, S., Sindhu, S., Robbins, J. R., Bauman, J., & Hsu, C. C. (2019). Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease. Head & neck, 41(12), 4076-4087.
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  Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high-risk nonendemic patients.
• Plonowska, K. A., Strohl, M. P., Wang, S. J., Ha, P. K., George, J. R., Heaton, C. M., El-Sayed, I. H., Mallen-St Clair, J., & Ryan, W. R. (2019). Human Papillomavirus-Associated Oropharyngeal Cancer: Patterns of Nodal Disease. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 160(3), 502-509.
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  To characterize patterns of neck lymph node (LN) metastases in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, represented by p16 positivity (p16+OPSCC).
• Sun, L., Chin, R. I., Gastman, B., Thorstad, W., Yom, S. S., Reddy, C. A., Nussenbaum, B., Wang, S. J., Knackstedt, T., Vidimos, A. T., Koyfman, S. A., & Manyam, B. V. (2019). Association of Disease Recurrence With Survival Outcomes in Patients With Cutaneous Squamous Cell Carcinoma of the Head and Neck Treated With Multimodality Therapy. JAMA dermatology, 155(4), 442-447.
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  It has previously been demonstrated that immunosuppressed patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) treated with surgery and postoperative radiotherapy have significantly inferior disease-related outcomes compared with immunocompetent patients, but data on outcomes after disease recurrence are limited.
• Wang, S. J. (2019). Salvage laryngectomy and laryngopharyngectomy: Multicenter review of outcomes associated with a reconstructive approach. Head & neck, 41(1), 16-29.
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  Surgeons have developed various reconstructive techniques to minimize the rate of pharyngocutaneous fistula and optimize functional outcome after salvage laryngectomy or laryngopharyngectomy.
• Liu, M., Wang, S. J., Benet, A., Meybodi, A. T., Tabani, H., & Ei-Sayed, I. H. (2018). Posterior auricular artery as a novel anatomic landmark for identification of the facial nerve: A cadaveric study. Head & neck, 40(7), 1461-1465.
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  Despite preservation techniques, performing a parotidectomy carries a transient facial nerve dysfunction rate in up to 65% of cases and a permanent facial nerve weakness rate of 4%-7%.
• Windon, M. J., D'Souza, G., Rettig, E. M., Westra, W. H., van Zante, A., Wang, S. J., Ryan, W. R., Mydlarz, W. K., Ha, P. K., Miles, B. A., Koch, W., Gourin, C., Eisele, D. W., & Fakhry, C. (2018). Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults. Cancer, 124(14), 2993-2999.
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  The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients.
• Yin, L. X., D'Souza, G., Westra, W. H., Wang, S. J., van Zante, A., Zhang, Y., Rettig, E. M., Ryan, W. R., Ha, P. K., Wentz, A., Koch, W., Eisele, D. W., & Fakhry, C. (2018). Prognostic factors for human papillomavirus-positive and negative oropharyngeal carcinomas. The Laryngoscope, 128(8), E287-E295.
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  Human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV-positive and HPV-negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratification STUDY DESIGN: Retrospective case series.
• Alemi, A. S., Heaton, C. M., Ryan, W. R., El-Sayed, I., & Wang, S. J. (2017). Volumetric Growth of Cervical Schwannoma as a Predictor of Surgical Intervention. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 156(1), 152-155.
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  Objective Cervical schwannomas are benign tumors that commonly present as asymptomatic masses and are managed with observation, radiation, or surgery. To our knowledge, the rate of volumetric change seen on serial imaging is not currently used to determine surgical candidacy. We assess average growth rates and determine whether growth rate of cervical schwannoma predicts having undergone surgery. Study Design Case series with chart review. Setting Quaternary academic medical center. Subjects and Methods Patients were identified with at least 2 imaging studies and pathologic or imaging characteristics of cervical schwannoma. Volume was calculated with the formula 4/3π xyz, with x, y, and z representing the 3 orthogonal dimensions. Volume and rate of volume change were compared among observed, surgical, and gamma knife groups. Results Thirteen patients were identified and divided into subgroups: surgical (n = 5), observation (n = 6), and gamma knife (n = 2). Mean follow-up time was 21 months (range, 1-80 months) and not significantly different among subgroups. The average changes in volume were 3.61 cm3/mo (entire group), -2.75 cm3/mo (observation), 11.97 cm3/mo (surgery), and 1.78 cm3/mo (gamma knife). Average initial volume for the entire group was 124.4 cm3 (range, 5-608 cm3) and 142 cm3 (range 5-613) at follow-up. The surgical group had a statistically significant change in volume ( P = .03). A statistically significant difference in growth rate was seen between the surgical and observation groups ( P = .016) and between the surgical group and all nonsurgical patients ( P = .011). Conclusions Rate of tumor growth can be used in the evaluation of patients with cervical schwannoma, and it may predict surgical intervention.
• Alemi, A. S., Seth, R., Heaton, C., Wang, S. J., & Knott, P. D. (2017). Comparison of Video and In-person Free Flap Assessment following Head and Neck Free Tissue Transfer. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 156(6), 1035-1040.
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  Objective Compare the efficiency of remote telehealth flap assessments with traditional in-person flap assessments. Study Design Observational study with retrospective review. Setting Tertiary academic medical center. Subjects and Methods All patients undergoing head and neck free tissue transfer were included in the study. All patients whose surgery was performed at hospital A underwent an in-person flap check overnight. Those at hospital B received a remote flap assessment. The primary outcome was total time spent performing the midnight flap assessment, including travel time. Data were gathered prospectively using an online survey. Results Sixty consecutive patients met inclusion criteria. On the night of the surgery, 31 had an in-person flap check while 29 had a video telehealth flap check. There were no partial or total flap losses or take-backs resulting from the flap checks. Mean (SD) times for in-person and remote assessments were 34 (16) minutes (range, 10-60 minutes) and 13 (8) minutes (range, 5-35 minutes), respectively ( P < .001). House staff unanimously felt the remote telehealth system improved their quality of life without affecting their perception of the quality of the flap assessment ( P = .001). Conclusion Compared with in-person flap assessments in this cohort, telehealth assessments allowed more efficient examination of free tissue reconstructions while yielding seemingly equivalent information. Therefore, remote telehealth flap checks may provide useful information supporting the use of high-fidelity remote data-streaming technology in the delivery of complex care to patients distant from their care provider.
• Bearelly, S., Wang, S. J., & Cheung, S. W. (2017). Oral sensory dysfunction following radiotherapy. The Laryngoscope, 127(10), 2282-2286.
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  To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls.
• Fakhry, C., Westra, W. H., Wang, S. J., van Zante, A., Zhang, Y., Rettig, E., Yin, L. X., Ryan, W. R., Ha, P. K., Wentz, A., Koch, W., Richmon, J. D., Eisele, D. W., & D'Souza, G. (2017). The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer. Cancer, 123(9), 1566-1575.
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  Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs).
• Hemmat, S. M., Wang, S. J., & Ryan, W. R. (2017). Neck Dissection Technique Commonality and Variance: A Survey on Neck Dissection Technique Preferences among Head and Neck Oncologic Surgeons in the American Head and Neck Society. International archives of otorhinolaryngology, 21(1), 8-16.
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  Introduction Neck dissection (ND) technique preferences are not well reported. Objective The objective of this study is to educate practitioners and trainees about surgical technique commonality and variance used by head and neck oncologic surgeons when performing a ND. Methods Online survey of surgeon members of the American Head and Neck Society (AHNS). Survey investigated respondents' demographic information, degree of surgical experience, ND technique preferences. Results In our study, 283 out of 1,010 (28%) AHNS surgeon members with a mean age of 50.3 years (range 32-77 years) completed surveys from 41 states and 24 countries. We found that 205 (72.4%) had completed a fellowship in head and neck surgical oncology. Also, 225 (79.5%) respondents reported completing more than 25 NDs per year. ND technique commonalities (>66% respondents) included: preserving level 5 (unless with suspicious lymph nodes (LN)), only excising the portion of sternocleidomastoid muscle involved with tumor, resecting lymphatic tissue en bloc, preservation of cervical sensory rootlets, not performing submandibular gland (SMG) transfer, placing one drain for unilateral selective NDs, and performing a ND after parotidectomy and thyroidectomy and before transcervical approaches to upper aerodigestive tract primary site. Variability existed in the sequence of LN levels excised, instrument preferences, criteria for drain removal, the timing of a ND with transoral upper aerodigestive tract primary site resections, and submandibular gland preservation. Results showed that 122 (43.1%) surgeons reported that they preserve the submandibular gland during the level 1b portion of a ND. Conclusions The commonalities and variances reported for the ND technique may help put individual preferences into context.
• Liu, M., Wang, S. J., Yang, X., & Peng, H. (2017). Diagnostic Efficacy of Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Meta-Analysis of 66 Studies. PloS one, 12(1), e0170322.
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  The diagnostic efficacy of sentinel lymph node biopsy(SLNB) in early oral squamous cell carcinoma(OSCC) still remains controversial. This meta-analysis was conducted to assess the diagnostic value of SLNB in clinically neck-negative T1-2 OSCC.
• Manyam, B. V., Garsa, A. A., Chin, R. I., Reddy, C. A., Gastman, B., Thorstad, W., Yom, S. S., Nussenbaum, B., Wang, S. J., Vidimos, A. T., & Koyfman, S. A. (2017). A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck. Cancer, 123(11), 2054-2060.
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  Patients who are chronically immunosuppressed have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN). This is the largest multi-institutional study to date investigating the effect of immune status on disease outcomes in patients with cSCC-HN who underwent surgery and received postoperative radiation therapy (RT).
• Markey, J. D., Morrel, W. G., Wang, S. J., & Ryan, W. R. (2017). The effect of submandibular gland preservation during level 1B neck dissection on postoperative xerostomia. Auris, nasus, larynx.
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  Compare the presence and degree of postoperative xerostomia following preservation or excision of the submandibular gland (SMG) during level IB neck dissection (ND) without adjuvant radiation.
• Naunheim, M., Wu, X., Ryan, W. R., Wang, S. J., & Heaton, C. M. (2017). Volumetric Growth Rate of Recurrent Pleomorphic Adenoma. The Annals of otology, rhinology, and laryngology, 126(7), 544-547.
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  Surgery for recurrent pleomorphic adenoma (PA) can be challenging and may increase the risk of operative complications, particularly facial nerve weakness. As observation may be a viable alternative to surgery for slow-growing tumors, our objective was to assess the growth rate of recurrent PAs.
• Tamplen, M. L., Tamplen, J., Shuman, E., Heaton, C. M., George, J. R., Wang, S. J., & Ryan, W. R. (2017). Comparison of Output Volume Thresholds for Drain Removal After Selective Lateral Neck Dissection: A Randomized Clinical Trial. JAMA otolaryngology-- head & neck surgery, 143(12), 1195-1199.
• Wang, S. J., Asthana, S., van Zante, A., Heaton, C. M., Phuchareon, J., Stein, L., Higuchi, S., Kishimoto, T., Chiu, C. Y., Olshen, A. B., McCormick, F., & Tetsu, O. (2017). Establishment and characterization of an oral tongue squamous cell carcinoma cell line from a never-smoking patient. Oral oncology, 69, 1-10.
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  The rising incidence of oral tongue squamous cell carcinoma (OTSCC) in patients who have never smoked and the paucity of knowledge of its biological behavior prompted us to develop a new cell line originating from a never-smoker.
• D'Souza, G., Westra, W. H., Wang, S. J., van Zante, A., Wentz, A., Kluz, N., Rettig, E., Ryan, W. R., Ha, P. K., Kang, H., Bishop, J., Quon, H., Kiess, A. P., Richmon, J. D., Eisele, D. W., & Fakhry, C. (2016). Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method. JAMA oncology.
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  Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear.
• Eisele, D. W., Wang, S. J., Prendes, B. L., Palefsky, J. M., & Groppo, E. R. (2016). Oral human papillomavirus infection in men who have sex with men with anal squamous intraepithelial lesions.. Head & neck, 38 Suppl 1(S1), E399-405. doi:10.1002/hed.24006
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  Little is known about the association between oral and anogenital human papillomavirus (HPV) infections..Oral and anal samples from 66 men who have sex with men with a history of HPV-related anogenital squamous intraepithelial lesions were analyzed using polymerase chain reaction (PCR), and typed for 38 HPV types..Prevalence of oral HPV infection was 30%, versus 82% for anal infection. Prevalence of oral and anal high-risk HPV infection was 11% and 64%, respectively. Concurrent oral-anal any-type HPV infection was found in 26% of participants, whereas concordant type-specific HPV prevalence was 5%. In multivariate analysis, number of partners from whom the participant received oral-penile sex and number of partners on whom the participant performed oral-penile sex were associated with oral HPV infection..Oral HPV prevalence in this cohort is high, however, concordant type-specific oral-anal HPV infection was rare. Increased risk of oral HPV infection was associated with oral-penile sex. © 2015 Wiley Periodicals, Inc. Head Neck 38: E399-E405, 2016.
• Wang, S. J., Ryan, W. R., & Hemmat, S. (2016). How, when, and from whom neck dissection operative technique is learned: An international survey on neck dissection education among head and neck oncologic surgeons.. American journal of otolaryngology, 37(5), 431-5. doi:10.1016/j.amjoto.2016.04.002
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  There is a paucity of evidence on how neck dissection (ND) technique is best learned..Online survey of the American Head and Neck Society (AHNS)..283 of the 1010 (28%) AHNS surgeon members completed the survey. Most respondents had 3-4 mentors [n=157 (55.5%)] that they felt were most influential their ND technique. 134 (47.3% of surgeons who completed a fellowship) felt that fellowship training had the most impact on their ND technique. Most respondents ranked the most effective methods of learning ND operative technique in the following order: 1) physically performing the operation yourself (70.1%), 2) observing the attending perform maneuvers independent of verbal teaching (37.7%) and 3) verbal teaching by an attending in the operating room independent of actual maneuvers (36.3%)..When learning an ND, the most benefit comes from empirical learning in the context a small group of surgeon mentors.
• Wang, S. J., Seth, R., Ryan, W. R., Markey, J. D., Knott, P. D., & El-sayed, I. H. (2016). Anterolateral Thigh Adipofascial Flap: A New Option for Scalp Reconstruction.. Journal of reconstructive microsurgery, 32(2), 160-3. doi:10.1055/s-0035-1558989
• Wang, S. J., South, A. P., Heaton, C. M., Faden, D. L., Derisi, J. L., & Arron, S. T. (2016). Targeted next-generation sequencing of TP53 in oral tongue carcinoma from non-smokers.. Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 45(1), 47. doi:10.1186/s40463-016-0160-4
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  Little is known regarding the etiology and genomic underpinnings of Oral Tongue Squamous Cell Carcinoma (OTSCC) in patients who lack traditional risk factors, yet the incidence is increasing. In particular, the rate, and role, of TP53 mutations in this cohort has been heavily debated in the literature..Tumor DNA from forty-three non-smokers with OTSCC underwent next generation sequencing of TP53..Sixty percent of samples contained a TP53 mutation. The G > T transversion rate was 5.7 %. TP53 status did not differ by age..OTSCC in non-smokers have TP53 mutation rates similar to other Head and Neck cancers yet these mutations do not appear related to carcinogen exposure based on the mutational spectrum and clinical history. The mechanisms driving tumorigenesis in this cohort, including mutations in TP53, remain elusive and further studies are needed.
• Yu, K., Wang, S. J., Ryan, W. R., Heaton, C. M., George, J. R., & Calkins, S. M. (2016). Clinicopathologic characteristics and outcomes of recurrent oropharyngeal squamous cell carcinoma.. American journal of otolaryngology, 37(6), 513-516. doi:10.1016/j.amjoto.2016.07.007
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  Positive p16 immunohistochemical staining is predictive of improved survival and response to treatment. The purpose of this study is to determine the clinicopathologic characteristics and outcomes of patients with p16+ oropharynx cancer who fail initial treatment..Case series including all patients with recurrent oropharyngeal squamous cell carcinoma from 2002 to 2014..Forty patients met inclusion criteria. Thirty-one (77.5%) tumors were p16+ and 9 (22.5%) were p16-. There was no difference in T/M stage at diagnosis; more patients with p16+ tumors presented initially with ≥N2 disease (p=0.04). Regional and/or metastatic recurrence was more common in the p16+ group as compared to the p16- group - 71% vs 22.2%, p=0.003. Outcomes for both groups were poor - 67.7% p16+ and 44.4% p16- patients died from disease..Compared to p16- recurrent tumor patients, p16+ recurrent tumor patients were more likely to experience regional or distant metastatic recurrence. Overall outcomes for both p16+ and p16- recurrent oropharynx tumors were poor.
• Hemmat, S. M., Wang, S. J., Uzelac, A., Yom, S. S., & Ryan, W. R. (2015). The Limitations of Routine Magnetic Resonance Imaging for Long-Term Post-Treatment Locoregional Surveillance of Salivary Carcinoma. ORL; journal for oto-rhino-laryngology and its related specialties, 77(3), 132-40.
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  To determine the utility of head and neck magnetic resonance imaging (HN-MRI) for the routine surveillance of patients without concurrent symptoms or signs of recurrence more than 6 months after treatment for salivary gland carcinoma (SGC).
• Wang, S. J. (2015). Surveillance radiologic imaging after treatment of oropharyngeal cancer: a review.. World journal of surgical oncology, 13(1), 94. doi:10.1186/s12957-015-0481-1
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  The increasing proportion of human papilloma virus-related oropharynx cancers has led to improved success in the treatment of this disease. However, the current low recurrence rate after treatment of oropharyngeal cancer highlights the continued need for, as well as the challenges of, designing an effective follow-up surveillance program. There are frequently multiple modalities used in the treatment of oropharyngeal cancer, resulting in short- and long-term tissue changes to the head and neck that challenge clinical distinction of recurrence versus treatment-related changes. The oropharynx subsite is characterized by complex anatomy not always accessible to physical exam, making radiologic imaging a potentially useful supplement for effective follow-up assessment. In this manuscript, the literature regarding the type of radiologic imaging modality and the frequency of obtaining imaging studies in the surveillance follow-up after treatment of oropharyngeal cancer is reviewed. While ultrasound and MRI have useful characteristics that deserve further study, PET/CT appears to have the best sensitivity and specificity for imaging surveillance follow-up of head and neck cancers including oropharyngeal cancer. A negative PET/CT is particularly useful as a predictor of prognosis and can guide the clinician as to when to stop obtaining additional imaging studies in the absence of clinical signs of recurrence. However, there is scant evidence that imaging surveillance can improve survival outcomes. Suggestions to guide future imaging surveillance research studies are provided.
• Wang, S. J., Prendes, B. L., Orloff, L. A., Glastonbury, C. M., & Bearelly, S. (2015). Transoral robotic-assisted surgical excision of a retropharyngeal parathyroid adenoma: a case report.. Head & neck, 37(11), E150-2. doi:10.1002/hed.24010
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  Transoral robotic surgery has been used with increasing frequency for oropharyngeal malignancies. We present the first known case of a transoral robotic-assisted parathyroidectomy..A 77-year-old woman with primary hyperparathyroidism was suspected of having a parathyroid adenoma. After several nonlocalizing single photon emission CT/CT sestamibi scans, a neck ultrasound revealed a suspicious low level 6 nodule. Surgical excision of this nodule proved to be a reactive lymph node. She then had a dynamic parathyroid protocol MRI and CT, which revealed a small retropharyngeal adenoma candidate. A transoral robotic-assisted surgical approach was utilized to bluntly dissect the retropharyngeal space just above the arytenoids to excise the nodule. After excision, the intraoperative parathyroid hormone (PTH) normalized and surgical pathology confirmed parathyroid adenoma..Transoral robotic-assisted surgery is a novel technique that can be utilized for resection of a parathyroid adenoma in the retropharyngeal space.
• White, H. N., Wang, S. J., Teng, M. S., Smith, R. V., Remacle, M., Moore, E. J., Miles, B. A., Mehta, V., Magnuson, J. S., Li, R., Lawson, G., Kupferman, M. E., Kraus, D. H., Koh, Y. W., Kiyosaki, K., Holsinger, F. C., Genden, E. M., Ganly, I., Ferris, R. L., , Duvvuri, U., et al. (2015). Oncologic Outcomes After Transoral Robotic Surgery: A Multi-institutional Study.. JAMA otolaryngology-- head & neck surgery, 141(12), 1043-1051. doi:10.1001/jamaoto.2015.1508
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  Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer..To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality..A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions..Select patients received radiation therapy and/or chemotherapy before or after TORS..Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors..Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis..This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.
• Yom, S. S., Wang, S. J., Uzelac, A., Ryan, W. R., & Al-shwaiheen, F. A. (2015). The advantages and drawbacks of routine magnetic resonance imaging for long-term post-treatment locoregional surveillance of oral cavity squamous cell carcinoma.. American journal of otolaryngology, 36(3), 415-23. doi:10.1016/j.amjoto.2015.01.024
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  Assess the clinical utility and accuracy of routine surveillance head and neck magnetic resonance imaging (HN-MRI) for the detection of locoregional recurrence in patients with a history of oral cavity squamous cell carcinoma (OCSCC) without concurrent suspicious symptoms or signs 6 months or more after treatment..For OCSCC patients who underwent routine (defined as: without concurrent suspicious symptoms or signs) surveillance HN-MRI at 6 months or more after treatment completion, we retrospectively determined the detection rate of locoregional disease and false positive rate..Out of an original cohort of 533 OCSCC patients, 46 patients, who were disease-free 6 months after treatment, had undergone 108 routine HN-MRIs from 6 to 48 months after surgery without the presence of concurrent suspicious symptoms or signs and had 6 months of subsequent follow up. 1 out of 46 (2.2%) had a true positive regional recurrence. 10 out of 46 (21.7%) patients experienced a false positive locoregional finding..Routine HN-MRI for locoregional surveillance of OCSCC, when used in patients without concurrent suspicious symptoms or exam findings over 6 months since treatment, may be unnecessary and costly given the very low rate of recurrence and high false positive rate. Our study supports the National Comprehensive Cancer Network guideline of limiting imaging after 6 months of primary treatment completion to patients with suspicious clinical findings. Nonetheless, managing physicians should continue to be empowered to use surveillance imaging based on risk profiles and unique circumstances for each patient.
• Zhang, G., Yang, X., Wang, S. J., Peng, H., Niu, X., & Chi, C. (2015). Sentinel node biopsy using indocyanine green in oral/oropharyngeal cancer.. World journal of surgical oncology, 13(1), 278. doi:10.1186/s12957-015-0691-6
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  Radioactive tracer-based detection has been proposed as a standard procedure in identifying sentinel nodes for cN0 oral/oropharyngeal carcinoma. However, access to radioactive isotopes may be limited in some surgical centers, and there is potential risk of the radioactive tracers to the operators. This study was designed to evaluate the feasibility of near-infrared fluorescence imaging with indocyanine green combined with blue dye mapping in sentinel node biopsy for cN0 oral/oropharyngeal carcinoma..Twenty-six cases of previously untreated oral/oropharyngeal carcinoma staged cT1-2N0M0 were enrolled in this study. One milliliter of indocyanine green (5 mg/ml) and 1.5 ml of methylene blue (1 mg/ml) were injected sequentially around the primary tumor in a four-quadrant pattern before skin incision. After elevation of the platysma flap and posterior retraction of the sternocleidomastoid muscle, fluorescence images were taken with a near-infrared detector, with special attention paid to any blue-dyed lymph nodes. Lymph nodes identified first with fluorescent hot spots with or without blue dye were defined as sentinel nodes, and they were harvested and sent for pathologic study..Sentinel nodes were successfully harvested in all 26 cases. The number of sentinel nodes (SNs) per case varied from 1 to 9, with an average of 3.4. Routine pathology demonstrated occult metastasis exclusively in SNs in four cases (15.4 %). No tracer-associated side effects occurred in this series..Near-infrared imaging using indocyanine green combined with methylene blue mapping is a feasible and reliable new method for SN biopsy in cN0 oral/oropharyngeal carcinoma.
• Wang, S. J., & Bearelly, S. (2014). Predictors of Salivary Fistulas in Patients Undergoing Salvage Total Laryngectomy.. International scholarly research notices, 2014, 373825. doi:10.1155/2014/373825
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  Background. Salivary fistula is a common complication after salvage total laryngectomy. Previous studies have not considered the number of layers of pharyngeal closure and have not classified fistulas according to severity. Our objective was to analyze our institutional experience with salvage total laryngectomy, categorize salivary fistulas based on severity, and study the effect of various pharyngeal closure techniques on fistula incidence. Methods. Retrospective analysis of 48 patients who underwent salvage total laryngectomy, comparing pharyngeal closure technique and use of a pectoralis major flap with regard to salivary fistula rate. Fistulas were categorized into major and minor fistulas based on whether operative intervention was required. Results. The major fistula rate was 18.8% (9/48) and the minor fistula rate was 29.2% (14/48). The overall (major plus minor) fistula rate was 47.9%. The overall fistula and major fistula rates decreased with increasing the number of closure layers and with use of a pectoralis major flap; however, these correlations did not reach statistical significance. Other than age, there were no clinicopathologic variables associated with salivary fistulas. Conclusion. For salvage total laryngectomies, increasing the number of closure layers or use of a pectoralis major flap may reduce the risk of salivary fistula.
• Wang, S. J., Kezirian, E. J., & Goepfert, R. P. (2014). Oral tongue squamous cell carcinoma in young women: a matched comparison-do outcomes justify treatment intensity?. ISRN otolaryngology, 2014, 529395. doi:10.1155/2014/529395
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  Background. The incidence of oral tongue squamous cell carcinoma (OTSCC) in young women is increasing with uncertain outcomes compared to traditional patients. Published outcomes data are at odds in this cohort of young women. Methods. Retrospective analysis comparing demographic, clinicopathologic, and outcomes data of women OTSCC patients younger than 45 years old matched 1 : 2 by stage with men both younger and older than 45 and women older than 45. Results. No disease-free or overall survival differences were found between cohorts. Young women were significantly more likely to receive radiation therapy, particularly in stage I disease, even when controlling for common pathologic indications. Conclusions. OTSCC in young women was not associated with worse outcomes compared to a matched cohort of other patients. Increased frequency of radiation treatment for this cohort may not be justified.
• Wang, S. J., Peng, H., & Li, W. (2014). Rare complication after thyroidectomy-cervical esophageal stenosis: a case report and literature review.. World journal of surgical oncology, 12(1), 308. doi:10.1186/1477-7819-12-308
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  The most common complications after thyroidectomy are injuries associated with the recurrent laryngeal nerve and parathyroid gland. Cervical esophagus perforation is an exceptionally rare complication after thyroidectomy; it can usually be resolved by conservative care. Cervical esophageal stenosis secondary to intraoperative esophageal injury during thyroidectomy is much rarer and has not been reported in the literature to date. We report a case of esophageal stenosis following thyroidectomy performed at a peripheral hospital. The patient initially underwent a thyroidectomy for papillary thyroid carcinoma involving the cervical esophagus; esophageal perforation was noted intraoperatively, and closed using three number 4 silk sutures. Cervical esophageal stenosis subsequently developed after conservative care. The patient was successfully treated with cervical esophagectomy and reconstruction using a tubed forearm free flap after a failed attempt at endoscopic recanalization. This case is discussed in conjunction with a review of the literature.
• Yang, X., Wang, S. J., Peng, H., Liu, M., Lin, J., & Guo, H. (2014). Modified radical neck dissection for residual neck disease after radiotherapy of nasopharyngeal carcinoma.. Auris, nasus, larynx, 41(5), 485-90. doi:10.1016/j.anl.2014.05.018
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  Although radical neck dissection is proposed as a standard salvage procedure for the management of radiotherapy-resistant nasopharyngeal carcinoma of the neck, modified radical neck dissection may be appropriate for select patients. This study was designed to evaluate the efficacy of individualized neck dissections based on preoperative imaging studies and intraoperative exploration for the management of radiotherapy-resistant nasopharyngeal carcinoma of the neck..The study included 42 consecutive patients who failed radiotherapy or chemo-radiotherapy for nasopharyngeal carcinoma of the neck and underwent a total of 46 radical neck dissections or modified radical neck dissections. Selection of the proper type of neck dissection was based on preoperative imaging studies and intraoperative exploration. The patients' clinical features, pathologic characteristics, complications, and treatment outcome were estimated and analyzed..Radical neck dissection and modified radical neck dissection were performed on 19 and 27 necks, respectively. Thirty-three necks (71.7%) had multiple node metastases. Nineteen necks (41.3%) had node metastases at two or more levels. The overall morbidity rate was 11.9%. The 5-year neck control rate (NCR) was 79.1% for 46 necks. The 5-year overall survival and disease free survival for 42 patients were 58.0% and 44.0%, respectively. No statistically significant differences were found in comparing OS, DFS, NCR between the MRND and RND groups..Individualized neck dissection based on preoperative imaging studies and intraoperative exploration is appropriate for the management of radiotherapy-resistant nasopharyngeal carcinoma of the neck.
• Yom, S. S., Wang, S. J., & George, J. R. (2014). Improved outcomes in adjuvant radiotherapy for oral cavity carcinoma at an academic center: a matched-pair analysis.. The Laryngoscope, 124(7), 1603-8. doi:10.1002/lary.24552
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  Our objective was to evaluate for outcomes differences for patients with oral cavity squamous cell carcinoma (OCSCC) who underwent primary surgical resection at an academic center (AC), followed by postoperative radiation therapy either at the AC or at a nonacademic radiation treatment center (non-AC)..Secondary analysis of a retrospective cohort of patients with previously untreated upper aerodigestive tract SCC who underwent surgery followed by adjuvant therapy at an AC from 2002 to 2012. Fifty-three matched pairs of OCSCC patients surgically treated at the AC, but receiving adjuvant radiation at either an AC or a non-AC, were evaluated for differences in clinicopathologic variables, radiation treatment metrics, and survival outcomes. The main outcome measures were overall survival, disease-specific survival, and locoregional control rates..Matched pairs were closely comparable in TNM (tumor, node, metastasis) stage, age, and gender. There were no significant between-groups differences in demographic and clinicopathologic variables except for smoking status (never smokers 43.3% for AC vs. 20.8% for non-AC; P=0.037). Non-AC OCSCC patients received a significantly lower total radiation dose (P=0.0004) and lower radiation fractional dose (P=0.0002) than their AC matched-pair counterparts. AC treatment was associated with improved overall survival (P=0.005), disease-specific survival (P=0.019), and locoregional control (P=0.016). AC treatment was an independent predictor of overall survival on multivariate analysis (P=0.044), after adjustment for clinicopathologic differences between groups..Improved survival for combined modality treatment of OCSCC at the AC was noted on multivariate analysis. Differences in key radiation treatment metrics could explain survival differences noted in this study..4.
• Zante, A. V., Wang, S. J., Tetsu, O., Heaton, C. M., & Durr, M. L. (2014). TP53 and CDKN2a mutations in never-smoker oral tongue squamous cell carcinoma.. The Laryngoscope, 124(7), E267-73. doi:10.1002/lary.24595
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  To determine the incidence and clinical significance of TP53 and CDKN2a somatic mutations in never smokers with oral tongue squamous cell carcinoma (OTSCC)..Case series..Fifty-one paraffin-embedded tumors from never smokers with OTSCC were obtained. p53 and p16 expression was determined by immunohistochemical (IHC) staining. Tumor DNA was amplified by polymerase chain reaction, and direct sequencing and mutation analysis was performed. Statistical relationships among p53 and p16 IHC findings, TP53 and CDKN2a mutation status, and clinicopathologic characteristics were determined. Univariate and multivariate Cox models for survival were performed..Sixteen tumors (31.4%) showed strong expression of p53 by IHC. There was no correlation between p53 status and clinicopathologic variables or survival outcomes. TP53 mutations were seen in 10 tumors (19.6%). Patients with TP53 mutations had higher tumor-node-metastasis (TNM) stage (P=0.049), worse tumor differentiation (P=0.025), earlier recurrence (P=0.024), and more often died from their disease (P=0.043) than those without mutations. Five tumors (9.8%) showed p16 positivity by IHC. There was no correlation between p16 status and clinicopathologic variables or survival. CDKN2a mutations were seen in four tumors (7.8%). Patients with CDKN2a mutations had earlier recurrence (P=0.019) and more often died from their disease (P=0.010) than those without mutations. Kaplan-Meier curves show worse disease-free survival (P=0.0162, P=0.0025) and overall survival (P=0.0095, P=0.0001) for TP53 and CDKN2a mutations, respectively. Multivariate analysis demonstrated that TP53 and CDKN2a mutations were independent predictors of disease-free survival (P=0.038 and P=0.039, respectively)..TP53 and CDKN2a mutations in never-smoker OTSCC are associated with worse clinicopathologic characteristics and poorer survival outcomes..N/A.
• Wang, S. J., Earle, C., Wong, G., & Bourguignon, L. Y. (2013). Role of hyaluronan synthase 2 to promote CD44-dependent oral cavity squamous cell carcinoma progression. Head & neck, 35(4), 511-20.
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  CD44 is a transmembrane receptor found on many different benign and malignant cells. Hyaluronan (HA), a major component of the extracellular matrix, is the primary ligand for CD44 receptors. In cancer cells, HA interaction with CD44 promotes multiple signaling pathways that influence tumor cell progression behaviors in a variety of solid tumors. Increasing evidence indicates that HA and CD44 signaling play an important role in oral cavity squamous cell carcinoma progression. HA is primarily synthesized by hyaluronan synthases, and the current study investigated the role of hyaluronan synthase 2 (HAS 2) in oral cavity carcinoma progression behaviors.
• Wang, S. J., Li, D., & Durr, M. L. (2013). Oral cavity squamous cell carcinoma in never smokers: analysis of clinicopathologic characteristics and survival.. American journal of otolaryngology, 34(5), 388-93. doi:10.1016/j.amjoto.2013.01.017
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  To examine the relationship between tobacco smoking history and the clinicopathologic and survival characteristics of patients with oral cavity squamous cell carcinoma (OCSCC)..This is a retrospective review of 531 patients treated for OCSCC from January 1998 to December 2009 at a tertiary care medical center..Thirty-two percent of OCSCC patients were never smokers. There were significant differences in tumor location between ever smokers and never smokers (p
• Wang, S. J., Ryan, W. R., & Heaton, C. M. (2013). Elective regional lymphadenectomy for advanced auricular squamous cell carcinoma. World Journal of Otorhinolaryngology, 3(1), 16-21. doi:10.5319/wjo.v3.i1.16
• Yang, X., Wang, S. J., Peng, H., Liu, M., & Guo, H. (2013). Infrahyoid myocutaneous flap for medium-sized head and neck defects: surgical outcome and technique modification.. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 148(1), 47-53. doi:10.1177/0194599812460211
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  To evaluate the surgical outcomes associated with infrahyoid myocutaneous flaps used in the reconstruction of medium-sized defects following head and neck cancer resection, as well as to discuss a novel technique modification..Case series with chart review..University cancer hospital..A total of 20 patients with oral or hypopharyngeal carcinoma who underwent infrahyoid myocutaneous flap reconstruction between June 2005 and December 2011 were retrospectively studied. A novel technical modification of flap harvest, preservation of the cranial portion of the anterior jugular vein, was attempted in 15 flaps and was successful in 13 flaps. Functional evaluation was performed in all patients 3 to 6 months after the operation or postoperative radiation..Total flap necrosis, marginal skin paddle necrosis, and total skin paddle loss were observed in 1, 2, and 1 patient(s), respectively. Pharyngocutaneous fistula without flap problem occurred in 1 patient. No flap complications occurred in 13 cases where the cranial portion of the anterior jugular vein was successfully preserved. Functional results were excellent in 16 patients, good in 3 patients, and fair in 1 patient..The infrahyoid myocutaneous flap is a reliable and convenient technique that can serve as an alternative to free flaps in the reconstruction of medium-sized defects of the oral cavity or hypopharynx. Preservation of the cranial portion of the anterior jugular vein is a novel technical modification of harvesting this flap, which may result in better venous return of the skin paddle and reduce skin paddle necrosis.
• Yom, S. S., Wang, S. J., & George, J. R. (2013). Combined modality treatment outcomes for head and neck cancer: comparison of postoperative radiation therapy at academic vs nonacademic medical centers.. JAMA otolaryngology-- head & neck surgery, 139(11), 1118-26. doi:10.1001/jamaoto.2013.4539
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  Patients with head and neck squamous cell carcinoma (HNSCC) who undergo surgical resection in an academic medical center (AC) often receive postoperative adjuvant external beam radiation therapy (RT) at non-ACs closer to home. Few data exist to compare outcomes of these populations..To evaluate treatment metrics and outcomes in patients with HNSCC who underwent surgical resection at an AC and then received postoperative adjuvant external beam RT at an AC vs a non-AC..Retrospective cohort study in 1 AC and several community RT non-ACs of patient with primary HNSCC treated with surgery at an AC followed by adjuvant therapy at an AC or a non-AC from January 1, 2002, to January 1, 2012..We evaluated for between-groups differences in demographics, RT metrics, and survival outcomes. Subgroup analysis by tumor site was then performed..Overall survival, disease-specific survival, and locoregional control rates..A total of 286 patients underwent surgery at the University of California, San Francisco, followed by adjuvant therapy. A total of 214 patients were analyzed. Significant differences in demographic and oncologic variables emerged, including important differences in RT metrics. Patients treated at a non-AC received a lower total RT dose, lower fractional dose, more delays in RT initiation, more breaks in RT, and more early termination of RT. Adjuvant treatment at an AC was associated with improved survival on univariate but not multivariate analysis. Subgroup analysis by SCC tumor site normalized many of the differences between groups, yet still revealed persistent differences in RT metrics. On multivariate analysis, AC treatment was not an independent predictor of survival for any tumor site..Better oncologic outcomes were seen in the AC group on univariate analysis, but these improved outcomes were not found on multivariate analysis. Important differences in RT metrics were noted for non-AC treatment sites compared with AC sites. Subgroup analysis by tumor site demonstrated persistent differences in treatment metrics. Standardization of adjuvant HNSCC treatment according to national guidelines should be prioritized at non-AC treatment facilities.
• Zante, A. V., Wang, S. J., Li, D., Kezirian, E. J., & Durr, M. L. (2013). Oral tongue squamous cell carcinoma in never-smokers: analysis of clinicopathologic characteristics and survival.. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 149(1), 89-96. doi:10.1177/0194599813482876
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  (1) To compare clinical characteristics, survival, and recurrence between never-smokers and ever-smokers with oral tongue squamous cell carcinoma (OTSCC). (2) To assess the relationship between clinicopathologic characteristics and survival/recurrence in OTSCC..Historical cohort study..Academic university medical center..This is a study of 120 patients with OTSCC who were treated from January 1999 to February 2010. Clinicopathologic factors were compared between never-smokers and ever-smokers using t tests and χ(2) tests. Cox regression analyses examined their association with survival and recurrence..Of 120 subjects, 66 (55%) were prior or current smokers. There were no significant differences in clinicopathologic factors between ever-smokers and never-smokers. After adjustment for clinicopathologic factors, multivariate Cox regression analysis demonstrated decreased overall survival for never-smokers, but this difference was not significant (hazard ratio [HR], 2.84; P = .056). Increased depth of tumor invasion (HR per millimter invasion, 1.09; P = .005), nodal metastasis (HR, 7.1; P = .025), and stage III or IV disease (HR, 9.45 and 7.31; P = .026 and .029, respectively) were associated with decreased overall survival. Perineural invasion (HR, 8.56; P = .005) and lymphovascular invasion (HR, 6.01; P = .011) were associated with disease recurrence..Overall survival may be decreased in never-smokers with OTSCC. Greater depth of tumor invasion and more advanced stage disease are associated with decreased survival. Perineural invasion and lymphovascular invasion are associated with disease recurrence.
• Wang, S. J., & Eisele, D. W. (2012). Parotidectomy--Anatomical considerations.. Clinical anatomy (New York, N.Y.), 25(1), 12-8. doi:10.1002/ca.21209
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  The parotid glands are paired major salivary glands and are located in the preauricular region. Parotidectomy is a surgical procedure that entails removal of all or a portion of the parotid gland. The most common indications for this operative procedure are a neoplasm of the parotid gland or metastases to parotid lymph nodes. An intimate knowledge of the anatomy of the parotid gland and related structures is necessary for the performance of safe and successful parotid surgery. This report will discuss the anatomy of the parotid gland as it pertains to parotid surgery and the avoidance of complications related to this surgery.
• Zante, A. V., Wang, S. J., Prendes, B. L., & Kangelaris, G. T. (2012). Pilomatricoma masquerading as metastatic squamous cell carcinoma. Grand Rounds, 12(1), 17-22. doi:10.1102/1470-5206.2012.0005
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  We present a case of a 58-year-old woman with a posterior neck mass who underwent fine-needle aspiration of the lesion, with initial cytopathologic evaluation being consistent with metastatic squamous cell carcinoma. However, following excisional biopsy of the tumor, histopathologic evaluation revealed a pilomatricoma. Appreciation of the difficulty in cytologic classification of this benign tumor and its propensity for confusion with more aggressive tumors may help prevent unintended and unnecessary invasive procedures as a result of erroneous diagnoses.
• Chen, C. P., Wang, S. J., van Zante, A., & Yom, S. S. (2011). Stepwise regional and distant progression of recurrent pleomorphic adenoma. Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 40(1), E5-10.
• Mannina, E. M., Pejavar, S. M., Glastonbury, C. M., van Zante, A., Wang, S. J., & Yom, S. S. (2011). Diagnosis of Bilateral Tonsil Cancers via Staging PET/CT: Case Report and Review. International journal of otolaryngology, 2011, 928240.
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  Diagnostic workup of metastatic head and neck squamous cell carcinoma of unknown primary site has traditionally included CT and/or MRI imaging and endoscopic biopsies. Routine bilateral tonsillectomy is highly controversial and the role of PET/CT is evolving, both for identification of potential primary sites and the detection of distant metastases. We report a case of cervical nodal metastasis of squamous cell carcinoma from an unknown primary site, in which dual-modality PET/CT led to the unexpected diagnosis of synchronous bilateral tonsillar cancers. In addition, PET/CT correctly distinguished pulmonary sarcoidosis from metastatic disease in this patient.
• Wang, S. J. (2011). What is the purpose of launching the World Journal of Otorhinolaryngology?. World Journal of Otorhinolaryngology, 1-3. doi:10.5319/wjo.v1.i1.1 Wang SJ. What is the purpose of launching the World Journal of Otorhinolaryngology? World J Otorhinolaryngol 2011; 1(1): 1-3 [DOI: 10.5319/wjo.v1.i1.1]
• Wang, S. J., & Bokhari, W. A. (2011). Modified Approach to the Cervicofacial Rotation Flap in Head and Neck Reconstruction. The Open Otorhinolaryngology Journal, 5(1), 18-24. doi:10.2174/1874428101105010018
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  Objectives: Large cutaneous defects of the cheek and external ear present a reconstructive challenge. While free tissue transfer has been increasingly used for such defects, many patients with these malignancies are poor candidates for lengthy reconstructive surgery. The cervicofacial and cervicothoracic advancement flaps have been previously described as a simple method for reconstructing defects of the face and neck. However, for large facial defects, these flaps typically require wide undermining with the final closure sometimes under tension. We describe our experience utilizing a modified approach to the cervicofacial rotation flap which has little tension of the defect closure and avoids incisions or undermining of tissue inferior to the clavicle. Study Design: Retrospective chart review. Methods: Sixteen patients underwent a modified cervicofacial rotation flap for immediate reconstruction of a cheek and/or total auriculectomy defect. Results: Primary cutaneous malignancies were the most common surgical indication, followed by parotid tumors with overlying skin involvement. Five patients had total auriculectomy defects while 11 patients had defects involving cheek skin without auriculectomy. Defect diameter size varied from 5 to 12 centimeters. Two patients required skin grafting of the donor site. Four patients had minor wound dehiscences that were treated with local wound care and allowed to close by secondary intention. Conclusions: We describe a modified approach to the cervicofacial rotation flap which minimizes undermining to provide a tension-free closure of the defect. Our approach is a simple, reliable method for coverage of large cutaneous defects involving the cheek and external ear.
• Wang, S. J., & Bourguignon, L. Y. (2011). Role of hyaluronan-mediated CD44 signaling in head and neck squamous cell carcinoma progression and chemoresistance.. The American journal of pathology, 178(3), 956-63. doi:10.1016/j.ajpath.2010.11.077
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  Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that may involve the oral cavity, pharynx, larynx, and paranasal sinuses. The mechanisms of tumor progression underlying the clinical behavior of HNSCC remain unclear. CD44 comprises a family of transmembrane receptors that can give rise to multiple CD44 variant isoforms. Hyaluronan (HA), a major extracellular matrix component is the primary ligand for CD44 receptors. HA and CD44 signaling play an important role in HNSCC progression. Several CD44 variant isoforms (including v3-, v6-, and v10-containing isoforms) are associated with advanced disease, possibly through unique growth factor interactions with binding domains in the inserted variant regions of the cytoplasmic domain of CD44. In HNSCC, HA mediates the formation of a complex including CD44 and the epidermal growth factor receptor (EGFR) which is overexpressed in a large proportion of HNSCCs. Downstream effectors under EGFR regulation are activated, promoting promote cell growth and tumor survival. The leukemia-associated Rho-guanine nucleotide exchange factor (LARG) also associates with CD44 and EGFR to promote several Ras and RhoA pathway effectors, leading to cell migration, growth, and tumor survival. The secretion of matrix metalloproteinases, necessary for tumor cell invasion, is also regulated by these HA/CD44-mediated pathways. Finally, EGFR-mediated pathways play major roles in the HA/CD44 promotion of chemoresistance in HNSCC. Understanding HA/CD44-mediated signaling pathways may lead to improved treatment of HNSCC.
• Wang, S. J., & Huoh, K. C. (2011). Poor Outcomes in Head and Neck Non-Melanoma Cutaneous Carcinomas §. The Open Otorhinolaryngology Journal, 5(1), 10-14. doi:10.2174/1874428101105010010
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  Objectives: Head and neck nonmelanoma cutaneous carcinomas (NMCC) may have poor outcomes, such as metastasis and recurrence. It remains unclear which patients are at increased risk for poor outcomes. We characterize a population of NMCC seen in a head and neck surgical practice. We sought to identify predictors of poor outcome in head and neck NMCC. Study Design: A retrospective cohort study of 161 patients with head and neck NMCC who presented to a university based otolaryngology-head and neck surgery practice over a 13 year period was performed. The study group included 127 men and 34 women, age range: 33 - 92 years. Subjects and Methods: Tumor characteristics of the study population were recorded, and statistical analysis and Kaplan- Meier survival calculations were performed to determine predictors of poor outcomes. Results: 113 squamous cell carcinomas (SCC) and 48 basal cell carcinomas (BCC) were identified. Among SCC patients, there was a 44% incidence of metastasis and a 47% incidence of recurrence. Among BCC patients, there was a 10% incidence of metastasis and a 50% incidence of recurrence. Twenty percent of SCC patients had a history of immunosuppression. Among SCC patients with immunosuppression, 83% had metastasis or recurrence. Survival for SCC patients with metastatic disease was significantly worse than patients without metastases. The presence of parotid metastases in SCC conferred a survival advantage when compared to other sites of metastases. Conclusion: The incidence of poor outcomes in NMCC was higher in our series than reported in the literature. Survival patterns of our study parallel those of similar studies in the literature.
• Wang, S. J., Rodriguez-bruno, K., & Ali, M. J. (2011). Role of panendoscopy to identify synchronous second primary malignancies in patients with oral cavity and oropharyngeal squamous cell carcinoma.. Head & neck, 33(7), 949-53. doi:10.1002/hed.21561
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  Tobacco use increases the risk for squamous cell carcinoma (SCC) of the upper aerodigestive tract. The reported incidence of synchronous second primary tumors in head and neck cancer is approximately 10%. Therefore, patients with oral cancer have routinely undergone "panendoscopy" consisting of direct laryngoscopy, bronchoscopy, and esophagoscopy. Recent studies indicate increasing numbers of upper aerodigestive tumors occurring in nonsmoking populations who may have a lesser risk for second primary tumors. The purpose of this study was to evaluate the utility of performing "panendoscopy" to identify second primary tumors in these patient populations..A retrospective study of 64 consecutive patients at a university head and neck surgery practice was performed. A cohort of patients with oral cavity or oropharyngeal SCC with no tobacco history who underwent diagnostic panendoscopy were compared with similarly staged patients with a current or past history of tobacco use. Operative reports were examined for synchronous primaries, and epidemiologic data were collected. Subgroup analysis of incidence of synchronous primaries with regard to smoking status, age, sex, T classification, N classification, and location of primary tumor was also carried out. Student's t test statistical analysis was used to ascertain significance..No synchronous second primary malignancies were discovered in the nonsmoking patients. In all, 12.1% of smoking patients were diagnosed with synchronous primary cancers on panendoscopy, and this difference was significant (p = .0392)..Routine panendoscopy of the upper aerodigestive tract in patients who have never smoked is unlikely to result in identification of synchronous second primary tumors.
• Wang, S. J., Orloff, L. A., & Eisele, D. W. (2010). Electrophysiologic facial nerve monitoring during parotidectomy.. Head & neck, 32(3), 399-405. doi:10.1002/hed.21190
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  Facial nerve monitoring is an adjunctive method available to a surgeon during parotid surgery to assist with the functional preservation of the facial nerve. This review describes the goals, applications, technique, and benefits of electrophysiologic facial nerve monitoring during parotid surgery. A review and analysis of the relevant medical literature related to electrophysiologic facial nerve monitoring during parotid surgery are included.
• Wang, S. J., Schell, H. M., Ryan, S. M., Rappazini, R., & El-sayed, I. H. (2010). Identifying and improving knowledge deficits of emergency airway management of tracheotomy and laryngectomy patients: a pilot patient safety initiative.. International journal of otolaryngology, 2010, 638742. doi:10.1155/2010/638742
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  Objectives. To evaluate the knowledge base of hospital staff regarding emergent airway management of tracheotomy and laryngectomy patients, and the impact of the introduction of a bedside airway form. Methods. Cross-sectional surveys of physicians, nurses, and respiratory therapists at a tertiary care hospital prior to and 24 months after introduction of a bedside Emergency Airway Access (EAA) form. Results. Pre- and postintervention surveys revealed several knowledge deficits. Preintervention, 37% of medical internists and 19% overall did not know that laryngectomy patients cannot be orally ventilated, and 67% of internists could not identify the purpose of stay sutures in recently created tracheotomies. Postintervention, these numbers improved for all groups. Furthermore, 80% of respiratory therapists reported encountering the EAA form in an emergent situation and found it useful. Conclusion. A knowledge deficit is identified in caregivers expected to provide emergency management of patients with airway anatomy altered by subspecialty surgeons. Safety initiatives such as the EAA form may improve knowledge among providers.
• Xia, W., Wang, S. J., Torre, C. D., & Bourguignon, L. Y. (2010). Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling.. Archives of otolaryngology--head & neck surgery, 136(5), 493-501. doi:10.1001/archoto.2010.25
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  To investigate whether hyaluronan (HA), a ligand for the transmembrane receptor CD44, and CD44, which acts through multiple signaling pathways to influence cellular behavior, promote Rho kinase- and phosphatidylinositol 3 (PI-3) kinase-mediated oncogenic signaling to alter cisplatin sensitivity and stimulate tumor cell proliferation, migration, and matrix metalloproteinase secretion in head and neck squamous cell carcinoma (HNSCC)..Laboratory investigation using the HNSCC cell line HSC-3..University laboratory..Rho kinase and PI-3 kinase activity, myosin phosphatase and AKT phosphorylation, tumor cell growth, migration, and matrix metalloproteinase secretion were measured in the presence or absence of HA, cisplatin, and inhibitors of Rho kinase and PI-3 kinase..The addition of HA, but not HA plus anti-CD44 antibody, resulted in increased Rho kinase and PI-3 kinase activity. Results of immunoblotting studies demonstrated that HA promotes Rho kinase-mediated myosin phosphatase phosphorylation and PI-3 kinase-mediated AKT phosphorylation. Hyaluronan was shown to promote migration and increased matrix metalloproteinase secretion through Rho kinase-mediated signaling. Hyaluronan treatment promoted increased tumor proliferation and resulted in a 12-fold reduced ability of cisplatin to cause HNSCC cell death. On the other hand, the presence of Y-27632, a Rho kinase inhibitor, and LY-294002, a PI-3 kinase inhibitor, blocked HA-mediated cisplatin resistance by HNSCC..Our results suggest that HA and CD44 promote Rho kinase- and PI-3 kinase-mediated oncogenic signaling and cisplatin resistance. Perturbation of HA-CD44-mediated Rho kinase and PI-3 kinase signaling pathways may be a novel strategy to treat HNSCC.
• Yom, S. S., Wang, S. J., Kangelaris, G. T., & Huang, K. (2010). Limited utility of routine surveillance MRI following chemoradiation for advanced-stage oropharynx carcinoma.. International journal of otolaryngology, 2010, 12844-12855. doi:10.1155/2010/904297
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  Objectives. To determine the utility of routine surveillance MRI in detecting locoregional recurrence following definitive chemoradiation in advanced-stage oropharynx carcinoma. Methods. We identified patients with Stage III-IV oropharynx carcinoma who were treated with chemoradiation between April 2000 and September 2004 and underwent longitudinal followup care at our institution. Patient charts were retrospectively reviewed for findings on MRI surveillance imaging, clinical signs and symptoms, and recurrence. Results. Forty patients received a total of 229 surveillance MRI scans with a minimum follow-up of three years (mean of 5.6 scans per patient). Six patients experienced false-positive surveillance studies that resulted in intervention. Four patients experienced recurrent disease, two of whom had new symptoms or exam findings that preceded radiographic identification of disease. Surveillance MRI scans identified recurrent disease in two asymptomatic patients who were salvaged, one of whom remains free of disease at follow-up. The overall sensitivity and specificity of the MRI surveillance program were 50 and 83 percent, respectively. The mean charge to each patient for the surveillance program was approximately $10,000 annually. Conclusion. In oropharyngeal cancer patients who have been treated with chemoradiation, an imaging surveillance program utilizing MRI produces limited opportunity for successful salvage.
• Wang, S. J., & Eisele, D. W. (2009). Role of surveillance radiologic imaging after treatment of oropharyngeal cancer. The Internet Journal of Otorhinolaryngology, 11(2).
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  Current trends in the treatment of oropharyngeal cancer include the increasing use of organ-preservation chemoradiation protocols. Reports in the recent literature have shown high success with this approach, with advanced stage III/IV oropharyngeal cancers having >80% 2and 3-year disease-free survival rates (1). Nonetheless, some oropharyngeal cancer patients do suffer recurrent disease, suggesting the need for post-treatment surveillance. The exact benefit of a surveillance program, the type of surveillance program, and the interval and duration of a surveillance program remain undefined. Because the oropharynx can be a difficult anatomic location to evaluate, and this evaluation may be further obscured by tissue changes wrought by cancer treatment, it has been generally assumed that physical examination alone is insufficient as a surveillance method for oropharyngeal cancer. Thus, radiologic imaging studies, in addition to the history and physical examination, have been commonly employed in cancer surveillance for this disease. The purpose of this manuscript is to review the evidence regarding the role of radiologic imaging for surveillance after chemoradiation treatment of oropharyngeal cancer.
• Wang, S. J., Wong, G., de Heer, A. M., Xia, W., & Bourguignon, L. Y. (2009). CD44 variant isoforms in head and neck squamous cell carcinoma progression. The Laryngoscope, 119(8), 1518-30.
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  The CD44 family of receptors includes multiple variant isoforms, several of which have been linked to malignant properties including migration, invasion, and metastasis. The objective of this study was to investigate the role of the CD44 v3, v6, and v10 variant isoforms in head and neck squamous cell carcinoma (HNSCC) tumor progression behaviors.
• Wang, S. J., Lin, D., Eisele, D. W., & Bucci, M. K. (2008). Squamous cell carcinoma of the buccal mucosa: a retrospective analysis of 22 cases.. Ear, nose, & throat journal, 87(10), 582-586. doi:10.1177/014556130808701014
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  We examined our institution's experience with 22 cases of previously untreated buccal squamous cell carcinoma via a retrospective chart review. Eleven of these patients had been treated with a combination of surgical excision and postoperative radiation therapy, 8 patients with surgical excision alone, and 3 patients with radiation therapy alone. The overall 3-year locoregional recurrence rate was 32% (n = 7). The 3-year survival rates were 82% after surgery plus radiation (9 of 11 patients), 63% after surgery alone (5 of 8), and 33% after radiation alone (1 of 3). Three-year T-category-specific survival rates were 100% for category T1 tumors (3 of 3 patients), 73% for T2 (8 of 11), 50% for T3 (3 of 6), and 50% for T4 (1 of 2). Although the small size of our study precluded any statistically significant conclusions, we believe that locoregional control and survival rates may be greater with surgical excision plus postoperative radiation than with treatment with either modality alone.
• Wang, S. J., Orloff, L. A., Gurney, T. A., & Eisele, D. W. (2008). Predictors of quality of life after treatment for oral cavity and oropharyngeal carcinoma.. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 139(2), 262-7. doi:10.1016/j.otohns.2008.05.024
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  Treatment for head and neck cancer, including surgery, radiation, and chemotherapy, can impact quality of life..Patients seen at an academic institution and treated for oral cavity and oropharyngeal carcinoma were asked to participate. The standardized University of Michigan Head and Neck Specific Quality of Life questionnaire was distributed..Eighty-seven patients completed the questionnaire. The majority had squamous cell carcinoma (94%), stage III or IV disease (53%), and a history of tobacco or alcohol dependence (59%), and were male (62%). Eighteen percent had free-tissue transfer (fibula free flap in 8% and radial forearm free flap in 10%). Predictors of worse quality of life included advanced stage, gastrostomy-tube dependence, complication, or recurrence..Stage, gastrostomy-tube dependence, complication, recurrence, and treatment modality influence quality of life. A better understanding of the impact of oral cavity and oropharyngeal cancer treatment on quality of life will enable us to better advise our patients.
• Bauer, J. A., Kumar, B., Cordell, K. G., Prince, M. E., Tran, H. H., Wolf, G. T., Chepeha, D. B., Teknos, T. N., Wang, S., Eisbruch, A., Tsien, C. I., Urba, S. G., Worden, F. P., Lee, J., Griffith, K. A., Taylor, J. M., D'Silva, N., Wang, S. J., Wolter, K. G., , Henson, B., et al. (2007). Targeting apoptosis to overcome cisplatin resistance: a translational study in head and neck cancer. International journal of radiation oncology, biology, physics, 69(2 Suppl), S106-8.
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  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.
• Lin, D., Glastonbury, C. M., Rafaelian, O., Eisele, D. W., & Wang, S. J. (2007). Management of advanced nodal disease following chemoradiation for head and neck squamous cell carcinoma: role of magnetic resonance imaging. The Journal of otolaryngology, 36(6), 350-6.
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  The purpose of this study was to determine the role of magnetic resonance imaging (MRI) to predict persistent nodal disease in head and neck cancer treated with chemoradiation.
• Mau, T., Pletcher, S. D., Cavanagh, P. W., Courey, M. S., & Wang, S. J. (2007). Minicricothyrotomy approach with fiberoptic guidance for management of posterior glottic stenosis. The Laryngoscope, 117(8), 1488-90.
• Rodriguez-Bruno, K., Ali, M. J., & Wang, S. J. (2007). Iatrogenic bilateral inverted papilloma: case report and literature review. The Journal of otolaryngology, 36(1), 72-5.
• Vakharia, K. T., Ali, M. J., & Wang, S. J. (2007). Quality-of-life impact of participation in a head and neck cancer support group. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 136(3), 405-10.
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  To assess if participation by patients in a head and neck cancer support group improves perceived quality of life (QOL).
• Wang, S. J., & Bokhari, W. A. (2007). Tongue reconstruction: recent advances.. Current opinion in otolaryngology & head and neck surgery, 15(4), 202-7. doi:10.1097/moo.0b013e3281fbd406
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  To examine the recent literature concerning advances in tongue reconstruction after tumor resection..Reconstruction following resection of malignant tongue tumors remains one of the most difficult problems in head and neck oncology. Recent trends in tongue reconstruction have focused on optimizing speech and swallowing function and maximizing quality of life. In the recent literature, several new reconstructive strategies including omohyoid musculocutaneous and myofascial flaps overlayed with radial forearm free flaps have been described. In addition, several older reconstructive options, such as trapezius and pectoralis rotational flaps, have been revisited. There has also been a trend toward restoring innervation to these flaps rather than leaving them insensate..Tongue cancer resection and subsequent reconstruction pose interesting challenges to the surgeon to maximize postoperative function and quality of life. Attention to the principles of tongue reconstruction and knowledge of the range of available reconstructive options can result in more favorable functional outcomes.
• Wang, S. J., Orloff, L. A., Moe, K. S., Kim, T. B., & Eisele, D. W. (2007). Full-thickness skin graft from the groin for coverage of the radial forearm free flap donor site.. American journal of otolaryngology, 28(5), 325-9. doi:10.1016/j.amjoto.2006.10.009
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  The purpose of this study is to describe the use of a full-thickness skin graft from the groin for coverage of the radial forearm free flap donor site. Our hypothesis is that the use of the full-thickness skin graft decreases morbidity and improves functional and cosmetic outcome at the skin graft donor site while also providing excellent coverage of the forearm donor site..This study used a retrospective chart review design..Patients undergoing radial forearm free flap reconstructions from 1995 to 2005 were included. Forty patients underwent radial forearm free flap reconstruction with closure of the forearm donor site with a full-thickness skin graft harvested from the groin. The inguinal donor site was closed primarily. Medical records including clinic notes, operative reports, and photographs were reviewed..There was 1 minor wound dehiscence at the groin site, and there were 5 minor forearm wound dehiscences with 2 cases of tendon exposure; all dehiscences were treated conservatively with local wound care. Both the groin wound and forearm donor sites healed satisfactorily in all cases, with no impairment of function related to the skin graft. All patients expressed satisfaction with the postoperative pain, functional outcome, and cosmetic appearance related to both the skin graft and forearm donor sites..Full-thickness skin graft from the groin for coverage of the radial forearm free flap donor site is an effective, safe alternative to the traditional split thickness skin graft.
• Wang, S. J., Peyrollier, K., & Bourguignon, L. Y. (2007). The influence of hyaluronan-CD44 interaction on topoisomerase II activity and etoposide cytotoxicity in head and neck cancer. Archives of otolaryngology--head & neck surgery, 133(3), 281-8.
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  To investigate the downstream molecular targets of hyaluronan (HA)-CD44 and phospholipase C (PLC)-mediated calcium ion (Ca(2+)) signaling in head and neck squamous cell carcinoma (HNSCC). Hyaluronan is a ligand for the CD44 receptor, which interacts with multiple signaling pathways to influence cellular behavior. We recently determined that HA-CD44 interaction promotes PLC-mediated Ca(2+) signaling and cisplatin resistance in HNSCC.
• Wreesmann, V. B., Wang, S. J., & Bourguignon, L. Y. (2007). Association of CD44 V3-containing isoforms with tumor cell growth, migration, matrix metalloproteinase expression, and lymph node metastasis in head and neck cancer.. Head & neck, 29(6), 550-8. doi:10.1002/hed.20544
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  The CD44 family of receptors includes multiple variant isoforms, some of which have been linked to tumor progression. The objective of this study was to investigate whether CD44 v3-containing isoforms are involved in head and neck squamous cell carcinoma (HNSCC) tumor progression..Laboratory investigation utilizing HNSCC cell lines and clinical tissue specimens was performed..Investigation of 13 HNSCC cell lines revealed a diversity of CD44 isoform profiles, including expression of CD44 v3-containing isoforms. Two cell lines, HOC313 and MDA1483, were selected for further study based on their CD44 v3 expression profile. The HOC313 cell line, which highly expresses CD44 v3-containing isoforms, demonstrated hyaluronan-mediated CD44-dependent promotion of tumor cell growth and migration. Conditioned media from the HOC313 cell line also exhibited high matrix metalloproteinase expression on gelatin zymography. Immunohistochemical analysis of a series of metastatic HNSCC lymph nodes revealed CD44 overexpression as well as staining for CD44 v3-containing isoforms..CD44 v3-containing isoforms are associated with HNSCC growth, migration, and matrix metalloproteinase activity and can be identified in lymph node metastasis.
• Wreesmann, V. B., Wang, S. J., Singh, B., Estilo, C. L., & Eisele, D. W. (2007). Downregulation of Fanconi anemia genes in sporadic head and neck squamous cell carcinoma.. ORL; journal for oto-rhino-laryngology and its related specialties, 69(4), 218-25. doi:10.1159/000101542
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  Much of our understanding of human cancer has come from studies of the hereditary cancer predisposition syndromes. Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA crosslinking agents, progressive bone marrow failure, and cancer predisposition to solid malignancies, especially head and neck squamous cell carcinoma (HNSCC). Since FA pathway-deficient cells are hypersensitive to DNA crosslinking chemotherapy agents, the presence of somatic FA gene inactivation in sporadic cancers may be of clinical interest. This study sought to determine the frequency of FA gene downregulation in sporadic HNSCC..The expression of the FA genes FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCJ, FANCL and FANCM in 11 HNSCC cell lines and 49 tongue carcinoma samples was studied with quantitative real-time polymerase chain reaction..Downregulation of at least one FA gene was observed in 3 of 11 HNSCC cell lines and 66% of tongue carcinoma samples. FANCB, FANCF, FANCJ and FANCM were most commonly affected by downregulation, whereas downregulation of FANCA, FANCE and FANCD2 was rare..Our data suggest that downregulation of FA genes is common in sporadic HNSCC. The clinical implications of this finding merit further study. .
• Wang, S. J., & Bourguignon, L. Y. (2006). Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer.. Archives of otolaryngology--head & neck surgery, 132(7), 771-8. doi:10.1001/archotol.132.7.771
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  To investigate whether hyaluronan (HA) and CD44 (hereinafter HA-CD44) promotes head and neck squamous cell carcinoma (HNSCC) chemotherapy resistance and whether HA-CD44 promotes epidermal growth factor receptor (EGFR)-mediated oncogenic signaling to alter chemotherapy sensitivity in HNSCC. Hyaluronan, a glycosaminoglycan component of the extracellular matrix, is a ligand for the transmembrane receptor CD44, which acts through multiple signaling pathways to influence cellular behavior. We recently determined that HA-CD44 promotes phospholipase C-mediated calcium signaling and cisplatin resistance in HNSCC..Cell line study..Tumor cell growth with various chemotherapeutic drugs (methotrexate, doxorubicin hydrochloride, adriamycin, and cisplatin) was measured in the presence or absence of HA and other inhibitors of the EGFR-mediated signaling pathway. Immunoblotting was used to study EGFR signaling. Migration assays provided one measure of tumor progression..The addition of HA, but not HA plus anti-CD44 antibody, resulted in a 2-fold reduced ability of methotrexate and an 8-fold reduced ability of adriamycin to cause HNSCC cell death. Immunoblotting studies demonstrated that HA can promote an association between CD44 and EGFR as well as CD44-dependent activation of EGFR-mediated signaling. Migration assays demonstrated that HA-CD44 can promote tumor migration with EGFR signaling. The presence of AG1478, an EGFR inhibitor, and U0126, an extracellular signal-regulated kinase inhibitor, inhibited HA-mediated tumor growth, migration, and chemotherapy resistance..Our results indicate that HA promotes CD44/EGFR interaction, EGFR-mediated oncogenic signaling, and chemotherapy resistance in HNSCC. Perturbation of HA-CD44-mediated signaling may be a promising and novel strategy to treat HNSCC.
• Wang, S. J., & Bourguignon, L. Y. (2006). Hyaluronan-CD44 promotes phospholipase C-mediated Ca2+ signaling and cisplatin resistance in head and neck cancer.. Archives of otolaryngology--head & neck surgery, 132(1), 19-24. doi:10.1001/archotol.132.1.19
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  To investigate whether hyaluronan (HA)-CD44 promotes head and neck squamous cell carcinoma (HNSCC) cisplatin resistance and whether HA-CD44 promotes phospholipase C (PLC)-mediated Ca2+ signaling to alter cisplatin sensitivity in HNSCC..Cell line study..Tumor cell growth with the chemotherapeutic drug cisplatin was measured in the presence or absence of HA, anti-CD44 antibody plus HA, and other inhibitors of the PLC-mediated Ca2+ signaling pathway. Ca2+ mobilization was measured with fluorescence spectrophotometry using the Ca2+ binding dye Fura/2AM..In the absence of HA, cisplatin inhibited tumor cell growth. The addition of HA, but not HA plus anti-CD44 antibody, resulted in a 5-fold reduced ability of cisplatin to cause HNSCC cell death, suggesting that HA can promote CD44-dependent cisplatin resistance. Fluorescence spectrophotometry demonstrated that HA can promote CD44-dependent Ca2+ mobilization in HNSCC. On the other hand, the presence of U73122, a PLC inhibitor, and 2-aminoethoxydiphenyl borate, an inositol-1,4,5-triphosphate receptor inhibitor, eliminated HA-mediated Ca2+ mobilization and HA-mediated cisplatin resistance in these cell lines..Our results indicate that HA-CD44 signaling influences cisplatin sensitivity in HNSCC cell growth. In particular, HA-CD44 promotion of PLC-mediated Ca2+ signaling plays a role in cisplatin resistance in HNSCC cells. Perturbation of this HA-CD44-mediated signaling pathway may be a promising target to overcome cisplatin resistance in HNSCC.
• Wolter, K. G., Wang, S. J., Henson, B. S., Wang, S., Griffith, K. A., Kumar, B., Chen, J., Carey, T. E., Bradford, C. R., & D'Silva, N. J. (2006). (-)-gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo. Neoplasia (New York, N.Y.), 8(3), 163-72.
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  Resistance to chemotherapy is a common problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC). Chemoresistant HNSCC tumors frequently overexpress antiapoptotic proteins, such as Bcl-x(L). (-)-gossypol, the negative enantiomer of a cottonseed polyphenol, binds to Bcl-x(L) and was recently been shown to inhibit HNSCC proliferation in vitro. In this study, we assessed the in vivo efficacy of (-)-gossypol in an orthotopic xenograft model of HNSCC, using two human HNSCC cell lines with high Bcl-x(L) expression levels. Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC, exhibiting growth and invasion into adjacent tissues. Mice were randomized into three groups: vehicle control and two daily intraperitoneal (-)-gossypol treatment groups (5 and 15 mg/kg). Tumors were measured twice weekly. In the control group, tumors grew progressively, whereas in (-)-gossypol treatment groups, tumor growth was significantly suppressed. The mitotic rate in tumors from (-)-gossypol-treated animals was significantly lower than that in controls, and an increase in the percentage of apoptotic cells was observed in treated tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks after cessation of (-)-gossypol treatment. Our results demonstrate that (-)-gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.
• Chepeha, D. B., Wang, S. J., Marentette, L. J., Bradford, C. R., Boyd, C. M., Prince, M. E., & Teknos, T. N. (2004). Restoration of the orbital aesthetic subunit in complex midface defects. The Laryngoscope, 114(10), 1706-13.
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  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.
• Chepeha, D. B., Wang, S. J., Marentette, L. J., Thompson, B. G., Prince, M. E., & Teknos, T. N. (2004). Radial forearm free tissue transfer reduces complications in salvage skull base surgery. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 131(6), 958-63.
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  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.
• Wang, S. J., Mintz, L. E., Natarajan, V., Lee, N. J., Srivatsan, E. S., & Wang, M. B. (2001). Third place--Resident Research Competition, AAO-2000. Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 124(6), 656-62.
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  Cyclin D1 is a regulatory factor essential in the progression of the cell cycle from G1 through S phase. Amplification and overexpression of cyclin D1 have been observed in many human cancers including head and neck squamous cell carcinoma (HNSCC). We have previously transfected a HNSCC control cell line (CCL23) with an antisense cyclin D1 plasmid and demonstrated inhibition of cell proliferation in vitro. In this study, we examine whether antisense cyclin D1 could inhibit tumor growth in vivo. Methods/measures: The CCL23 and its antisense cyclin D1 transfected clone (CCL23 AS) were injected into the flanks of nude mice. Tumor growth was monitored weekly. After 5 weeks, tumors were removed and studied for tumor size, cyclin D1 expression, cyclin D1-dependent kinase activity, and retinoblastoma (Rb) phosphorylation.
• Lee, N. J., Wang, S. J., Durairaj, K. K., Srivatsan, E. S., & Wang, M. B. (2000). Increased expression of transforming growth factor-beta1, acidic fibroblast growth factor, and basic fibroblast growth factor in fetal versus adult fibroblast cell lines. The Laryngoscope, 110(4), 616-9.
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  Fetal wound healing occurs without scar tissue formation. Differences in growth factor expression between fetal and adult fibroblasts have been explored. Recently we used RNA expression studies to demonstrate that transforming growth factor (TGF)-beta1, acidic fibroblast growth factor (alpha-FGF), and basic fibroblast growth factor (beta-FGF) could be detected in both fetal and adult fibroblast cell lines. In addition, adult fibroblasts showed greater relative expression of these growth factors than fetal fibroblasts. The aim of this study was to identify the level of protein expression in fetal and adult fibroblasts.
• Wang, S. J., Sercarz, J. A., Lufkin, R. B., Borges, A., & Wang, M. B. (2000). MRI-guided needle localization in the head and neck using contemporaneous imaging in an open configuration system. Head & neck, 22(4), 355-9.
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  MRI-guided procedures have previously been limited by technical difficulties, including the need for MRI-compatible instruments, slow image acquisition time, and the closed nature of conventional MRI scanners. The development of open configuration MRI systems with in-room, contemporaneous imaging has greatly increased the potential for MRI-guided interventional procedures. We evaluate our clinical experience applying this technology to the head and neck.
• Wang, S. J., Wang, M. B., Barauskas, T. M., & Calcaterra, T. C. (2000). Surgical management of carotid body tumors. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 123(3), 202-6.
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  The goal was to review our experience in the management of carotid body tumors at a tertiary referral center.
• Wang, S. J., Wang, M. B., Yip, H., & Calcaterra, T. C. (2000). Combined radiotherapy with planned neck dissection for small head and neck cancers with advanced cervical metastases. The Laryngoscope, 110(11), 1794-7.
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  We have previously described our treatment algorithm for patients with small head and neck cancers with advanced cervical metastases (stage N2 or greater). Primary radiotherapy is given to the primary site and neck, followed 6 weeks later with endoscopy and biopsy of the primary site. If biopsy of the primary site is negative by frozen section, an immediate neck dissection is performed even when no clinical residual neck disease is present. Our initial review found that 36% of patients with a complete clinical response to radiotherapy had positive nodes on histological examination.
• Wang, S. J., Borges, A., Lufkin, R. B., Sercarz, J. A., & Wang, M. B. (1999). Chondroid tumors of the larynx: computed tomography findings. American journal of otolaryngology, 20(6), 379-82.
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  Chondromas and chondrosarcomas of the larynx are rare cartilaginous tumors making up less than 1% of all laryngeal tumors. Patients typically present with symptoms of hoarseness, dysphagia, or dyspnea. The most common location in the larynx for these tumors is the cricoid cartilage. Radiographically, these lesions are typically hypodense, well-circumscribed masses containing mottled calcifications with smooth walls centered within the cartilage.
• Wang, S. J., Sercarz, J. A., Blackwell, K. E., Aghamohammadi, M., & Wang, M. B. (1999). Open bedside tracheotomy in the intensive care unit. The Laryngoscope, 109(6), 891-3.
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  To demonstrate that open bedside tracheotomy is an efficient, safe, and cost-effective procedure.
• Wang, S. J., Wang, M. B., & Calcaterra, T. C. (1999). Radiotherapy followed by neck dissection for small head and neck cancers with advanced cervical metastases. The Annals of otology, rhinology, and laryngology, 108(2), 128-31.
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  Patients with small or occult primary carcinomas of the head and neck with advanced cervical metastases present a difficult problem for the otolaryngologist. A retrospective review was performed of patients who presented to UCLA Medical Center between January 1986 and June 1996 with small or occult primary tumors of the head and neck with advanced cervical metastases. The treatment algorithm consisted of initial radiotherapy to the primary site and the neck, followed in 6 to 8 weeks with endoscopy and biopsy of the primary tumor site. As long as the repeat biopsy of the primary tumor site was negative by frozen section, an immediate neck dissection was performed, even if no residual neck disease was present. Almost 40% of patients with no clinical evidence of neck disease following radiotherapy had evidence of metastatic cancer on histopathologic examination. While some would consider a watchful waiting policy when there is no clinically detectable neck disease following radiotherapy, we believe it is preferable to perform immediate surgery in such patients, in light of the high incidence of microscopic metastatic disease.