winter newsletter 2011

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The Ohio State University Medical Center Department of Otolaryngology – Head and Neck Surgery Winter 2011 Dear Friends, It has been another eventful and wonderful year in the Department of Otolaryngology – Head and Neck Surgery here at The Ohio State University. We appreciate all who have made the past year possible, as well as our many colleagues and friends around the country and world with whom we enjoy rich and rewarding associations. Within this report you will find a few highlights of the past year in our continual pursuit of excellence, including: An honor by the Medical Center again as the Department with the highest patient satisfac- tion ratings. This is gratifying as the scores from all departments have continued to rise. The announcement that Dr. David E. Schuller and his team received a $100 million competitive grant from the U.S. Department of Health and Human Services to support the largest construction project in the history of The Ohio State University. See information on this proposed new facility on the next page. The renewal by Dr. Susan Nittrouer and her team in Communication Sciences of two competitive R01 grants and the receipt of new NIH funding for a project led by Dr. Tony Shahin. The receipt of further RO1 funding by Dr. Quintin Pan in conjunction with Dr. Ted Teknos and their research team for their translational research in oral squamous cell carcinoma from the NCI. We were joined this year by Dr. Kris Jatana, who completed his pediatric otolaryngology fellowship with Dr. Lauren Holinger in July. Kris also completed his residency with us. He is an excellent clinician/scientist with interest in pediat- ric oncology, and he has excellent research productivity. We are fortunate to have him join our ranks. Dr. Paul Levine, professor and chair of the University of Virginia, Department of Otolaryngology, will be our honored guest at the 19th Annual William H. Saunders Symposium, June 24-25, 2011. Please join us. We wish you all the best in this New Year. With best regards, D. Bradley Welling, MD, PhD, FACS Professor and Chair Department of Otolaryngology Head and Neck Surgery The Ohio State University Medical Center Eye and Ear Institute 915 Olentangy River Road., 4th Floor Columbus, OH 43212 office 614-293-8706 fax 614-293-7292 [email protected] Message from the Department Chair Inside this Issue: Medical Center Expansion Kickoff, Clinical Trials Active in 2009/2010, Summer Data Camps for Deaf Children, Robotic Thyroid- ectomy, Temporal Bone Simulation Project, NIH Research Funding, New House Staff, Highlight: Quintin Pan, PhD, Publications for 2009/2010

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Otolaryngology Newsletter, Winter 2011

TRANSCRIPT

The Ohio State University Medical Center

Department of Otolaryngology –Head and Neck Surgery

Winter 2011

Dear Friends,

It has been another eventful and wonderful year in the Department of Otolaryngology – Head and Neck Surgery here at The Ohio State University. We appreciate all who have made the past year possible, as well as our many colleagues and friends around the country and world with whom we enjoy rich and rewarding associations.

Within this report you will find a few highlights of the past year in our continual pursuit of excellence, including:

• An honor by the Medical Center again as the Department with the highest patient satisfac-tion ratings. This is gratifying as the scores from all departments have continued to rise.

• The announcement that Dr. David E. Schuller and his team received a $100 million competitive grant from the U.S. Department of Health and Human Services to support the largest construction project in the history of The Ohio State University. See information on this proposed new facility on the next page.

• The renewal by Dr. Susan Nittrouer and her team in Communication Sciences of two competitive R01 grants and the receipt of new NIH funding for a project led by Dr. Tony Shahin.

• The receipt of further RO1 funding by Dr. Quintin Pan in conjunction with Dr. Ted Teknos and their research team for their translational research in oral squamous cell carcinoma from the NCI.

• We were joined this year by Dr. Kris Jatana, who completed his pediatric otolaryngology fellowship with Dr. Lauren Holinger in July. Kris also completed his residency with us. He is an excellent clinician/scientist with interest in pediat-ric oncology, and he has excellent research productivity. We are fortunate to have him join our ranks.

• Dr. Paul Levine, professor and chair of the University of Virginia, Department of Otolaryngology, will be our honored guest at the 19th Annual William H. Saunders Symposium, June 24-25, 2011. Please join us.

We wish you all the best in this New Year.

With best regards,

D. Bradley Welling, MD, PhD, FACSProfessor and ChairDepartment of Otolaryngology Head and Neck SurgeryThe Ohio State University Medical CenterEye and Ear Institute915 Olentangy River Road., 4th FloorColumbus, OH 43212office 614-293-8706 fax 614-293-7292 [email protected]

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Inside this Issue: Medical Center Expansion Kickoff, Clinical Trials Active

in 2009/2010, Summer Data Camps for Deaf Children, Robotic Thyroid-

ectomy, Temporal Bone Simulation Project, NIH Research Funding, New

House Staff, Highlight: Quintin Pan, PhD, Publications for 2009/2010

Medical Center Expansion: Construction Kicks Off on Ohio State’s New Cancer Hospital

For the 17th year in a row, U.S.News & World Report ranked Ohio State’s

Department of Otolaryngology as one of the best ear, nose and throat

programs in the nation. The rankings are based on discharges, resident’s

scores on national tests and reputation. Our Department advanced 13

positions in the rankings this year to No. 18 in the country – an outstanding

achievement. The Ohio State University Medical Center was also named to

the U.S. News Honor Roll for the first time ever. Of the 4,861 hospitals con-

sidered, only 21 made the Honor Roll, and Ohio State was the only hospital

in central Ohio to make the list. Our hospitals were ranked in 10 special-

ties, and our ranking of 18th helped the Medical Center achieve this highly

touted accomplishment.

A new era of cancer care and research at The Ohio State University Medical Center began June 18th with the groundbreaking of a $1 billion expansion project that includes construction of a 17-story medical tower that will house a new Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) and an equally innovative critical care hospital.

Completion of the new 276-bed cancer hospital and 144-bed critical care hospital is slated for 2014.

The design of the tower will place can-cer researchers closer to clinicians, to promote their interaction and to expedite discoveries and their translation to patient care. It also emphasizes the education of future healthcare professionals, particu-larly in P4 Medicine: health care that is predictive, preventive, personalized and participatory.

The largest construction initiative in University history, the Medical Center expansion will create 5,000 construction jobs over the next four years and at least 6,000 full-time positions at the University from 2008-15.

Michael Caligiuri, MD, OSUCCC director and James CEO, and David Schuller, MD, vice president for Expansion and Outreach, spoke at the June ceremony, both noting that the groundbreaking was held nearly 20 years to the day that the present James Cancer Hospital and Solove Research Institute opened in July 1990.

“We’re all here today because a generation of people be-fore us was willing to invest in the future, to create the en-vironment in which we now prosper,” Caligiuri said. “Now, it is our turn to build the future for the next generation.”

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The Ohio State University Medical Center Department of Otolaryngology page 2

Ohio State University Department of Otolaryngology Ranked as One of the Best in Nation

Clinical Trials Active in 2009/2010

PI Division Title

Charles Elmaraghy, MD Pediatric Otolaryngology Incidence of Vestibular Stenosis in NICU Kris Jatana, MD Patients on Nasal CPAP

Enver Ozer, MD Head and Neck Oncology A Pilot Study Assessing Transoral Robotic Surgery (TORS) for Oral and Laryngopha- ryngeal Benign and Malignant Lesions Using the Da Vinci Robotic Surgical System

D. Bradley Welling, MD, PhD Otology, Neurotology, Exploration and Estimation of Intratumoral Cranial Base Surgery Concentration and Activity of Lapatinib in Vivo in Vestibular Schwannomas

D. Bradley Welling, MD, PhD Otology, Neurotology, Evaluation of the Nucleus Hybrid L24 Cranial Base Surgery Cochlear Implant System

Amit Agrawal, MD Head and Neck Oncology Food-Based Modulation of Biomarkers in Human Tissues at High Risk for Oral Cancer

Amit Agrawal, MD Head and Neck Oncology A Phase 3, Prospective, Open-Label, Multicenter Study of Lymphoseek® as Lymphoid Tissue Targeting Agent in Patients With Known Cutaneous or Mucosal Head and Neck Squamous Cell Carcinoma Who Are Undergoing Lymphadenectomy

Clinical Trials

The Ohio State University Medical Center Department of Otolaryngology page 3

For more information on the Department’s clinical trials, contact:

Mark Inman 915 Olentangy River Road Phone: 614-293-3470

Summer Data Camps for Deaf Children

Congenital deafness is the most prevalent birth defect there is. Roughly three in every thousand babies are born with some de-gree of hearing loss. Add to this statistic the fact that congenital hearing loss can profoundly and permanently affect the quality of an individual’s life and we find compelling reason to want to investigate ways to mitigate those effects. And that is exactly what a grant from the National Institute on Deafness and Other Communication Disorders to Susan Nittrouer, PhD, has been doing since 2003: examining the factors that might mitigate the deleterious consequences of congenital hearing loss.

For the first five years of this project, children with severe to profound hearing loss, as well as normal-hearing control subjects, were tested every six months on their birth date. These children lived in all corners of the country, but shared common character-istics. If deaf, the children had all been identified before the age of 30 months. These 119 deaf children all received amplifica-tion shortly after being identified (and before 30 months) and were obtaining intervention services at least once per week from pro-fessionals with at least master’s degrees in speech-language pathology or deaf education. In sum, these were the lucky ones: children born with significant hearing loss who were able to access the resources needed to help them achieve the best they could. Furthermore, the parents of all these deaf children were able to verbalize explicitly that they wanted their children to grow up competent in spoken language, without the need of sign language for academic support or personal interactions.

The 205 children enrolled in this study were tested according to rigorous protocols on tasks looking at their cognitive develop-ment, their social and adaptive behaviors and, most importantly, their levels of language performance. Not only were standardized instruments used in these protocols, detailed and labor-intensive methods of quantifying language production were also imple-

mented. The results of those first five years produced some im-portant data concerning ways that we could be intervening with these children. Overall, the data revealed that early identification and high-end technologies, such as cochlear implants, are not enough. Deaf children, even the lucky ones, are still not reach-ing the levels of the language performance their normal-hearing peers take for granted.

Based on the strength of those outcomes, this research project was re-funded for an additional five years. This time, though, chil-

dren would not be tested in their hometowns. Instead, these same children who participated in the past, and their parents, are travel-ing to Columbus, Ohio, for two days of intensive testing at what we have termed “data camps.” The children attend in groups of four to six families. During the day, they are tested at our new state-of-the-art research facilities at the Eye and Ear Institute on Olentangy River Road. At night, they swim and play together at local hotels. Parents complete questionnaires about their own abilities to cope with the stress related to having

a deaf child and about their children’s behavior. The goal of this second grant cycle is to explore children’s performance in the early elementary grades.

The summer of 2010 was the first year that these camps took place. For the most part, the children who attended were just finishing kindergarten. Over the next four years, we will continue to bring these children to our data camps, following their lan-guage and academic development through fourth grade. No such longitudinal data currently exist for deaf children. The results are already challenging some traditional and strongly held beliefs concerning how we must intervene, and offering some fresh insights into what might help children such as these reach the heights they are capable of reaching, unhindered by deafness.

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Congenital hearing loss is a condition that used to create lifelong communication deficits for those afflicted. Individuals could learn to communicate using sign language, but the chances of developing effective spoken language were extremely limited. This led to occupational, financial and social limitations for deaf individuals, especially because 96 percent of children born with hearing loss have parents with normal hearing.

The development of cochlear implants has dramatically im-proved the chances of deaf children learning spoken language,

but intensive early intervention is needed if these children are to take advantage of the signal provided by these devices. The Department of Otolaryngology at The Ohio State University, along with its affiliated clinical faculty at Nationwide Children’s Hospital, is the primary provider of cochlear implants to pediatric patients in central Ohio. For that reason, we are keenly interested in exploring what helps deaf children acquire effective spoken language

continued on back cover

Department of Otolaryngology hosts Summer Data Camps for Deaf Children

The Ohio State University Medical Center Department of Otolaryngology page 4

Enver Ozer MD, Performs First Robotic Thyroidectomy in Central OhioEnver O

zer MD

With just a small, hidden incision in the patient’s armpit, one of our head and neck surgeons, Dr. Enver Ozer, performs robotic-assisted surgery to remove a diseased thyroid without leaving a visible scar on the patient’s neck.

Only about 35 medical centers nationwide offer such minimally invasive robotic thyroidectomies, and Ozer, a head and neck cancer surgeon at The Ohio State University Com-prehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), is the first in central Ohio to perform the procedure.

The da Vinci® Surgical System is pow-ered by state-of-the-art robotic tech-nology. It provides the surgeon with four arms to operate and is incredibly precise in its movements.

Robotics have been used in heart and prostate surgeries for years with U.S. Food and Drug Administration (FDA) approval. Enver Ozer, MD, one of the experienced surgeons in the Head and Neck Program, has started using this safe and minimally invasive technique for the treatment of head and neck disorders, including cancers of the tonsils, voice box and the back of the tongue, as part of an innovative clinical trial at the OSUCCC – James since 2007. Now he is using this technology for the treatment of thyroid diseases.

Such minimally invasive techniques involve fewer incisions, less blood loss, less pain, and shorter hospital stays and recovery times, said Ozer, who specializes in otolaryngology – head and

neck surgery and robotic-assisted surgery. He adds that most pa-tients are discharged from the hospital within one to three days.

Ozer is one of 25 skilled surgeons at Ohio State’s Center for Ad-vanced Robotic Surgery, an international training center featuring expertise in more than 70 robotic procedures for more than 25

different conditions, including complex cases, said center co-director Dr. Ron-ney Abaza.

“A major benefit of this type of surgery is that it doesn’t leave a scar on the patient’s neck,” said Ozer. “A typical open surgery to remove the thyroid can leave a visible scar up to 3 inches long on the base of the neck. But this surgery involves a small hidden incision in the armpit, without any neck incision. We make a small tunnel under the skin to the thyroid area and remove the thyroid through that tunnel.”

Robotic-assisted surgeries use small incisions for instrumentation and for a miniature camera. The surgeon per-forms the surgery by manipulating the robotic instrumentation while seated at a console and looking through a viewfinder at magnified images trans-mitted from inside the patient’s body via the miniature camera.

Ozer is also one of the charter members of the Society of Robotic Surgery, which is a global society founded on the fundamental principles of education and collaboration as a means to tackle the complex issues of robotic surgery.

Ohio State physicians perform about 1,200 robotic surgeries a year.

The Ohio State University Medical Center Department of Otolaryngology page 5

Four months after the surgery with no neck scar and a hidden right arm pit incision

Positioning the robotic arm in the surgical field is one of the critical steps of the surgery

Temporal Bone Simulation Project – An Update

We have concluded our R01, DC06458-01A1, “Validation/Dis-semination of Virtual Temporal Bone Dissection,” funded by the National Institute on Deafness and Other Communication Dis-orders. The follow-up proposal, “Virtual Temporal Bone Surgery: Defining and Translating Standardized Metrics to An Automated Assessment Tool,” was submitted Oct. 13, 2010.

The objective of the effort is to develop, test, and improve a simulation environment for education of basic otologic surgical techniques. This includes a multi-institutional (See Table 1) study to determine the efficacy of simulated environments within the residency curriculum.

Osseous data is acquired using clinical CT and research micro-CT imaging systems. The synthetic environment includes a computer with a graphical processing unit (GPU), stereo speak-ers, stereo monitor with glasses, and haptic devices to provide force-feedback and tool interaction (See Figure 1). 3-D volume data is used as a representation of the regional anatomy. This data, combined with user interaction, is used to calculate the resulting sounds, forces, and visuals to emulate a mastoidectomy procedure.

The results demonstrate an effective environment for initial training in otological technique. The system is currently being improved for use in a multi-institutional study to consensually determine objective performance standards. These standards will be integrated to evaluate the use of the system as an automated assessment tool of surgical performance. Advanced rendering techniques have been developed using the GPU to maintain high performance, and have been employed to incorporate a fluid module to simulate blood and other fluid during drilling (See Figure 2). Also being developed are algorithms to automatically generate a score representing the quality of the mastoidectomy performed in the simulator.

We would like to thank the Department for everyone’s continued support and effort to move the project forward, especially Dr. Dodson’s and Dr. Welling’s efforts to assist in grading the tempo-ral bones necessary for the study.

A movie of the simulation is available anonymously at: http://www.youtube.com/watch?v=Y_6finmrqao

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The Ohio State University Medical Center Department of Otolaryngology page 6

Stanford University Duke Texas Southwestern Henry Ford of Iowa Health System

University University of University of Johns Hopkins Albert Einstein of Mississippi Cincinnati California University at Irvine

Left: Dr. Gregory Wiet using the temporal bone simulation environment

Table 1: Table of participating institutions.

Above: View from simulator showing depiction of suction/irriagation and bleeding effects

NIH Research FundingN

IH R

esearch Funding

The Ohio State University Medical Center Department of Otolaryngology page 7

Amit Agrawal, MD Christopher Weghorst, PhD 12/01/07-8/30/12 NIH/NCIR01CA127368The Ohio State University Food-Based Modulation of Biomarkers in Human Tissues at High Risk for Oral Cancer

This novel translational study will provide essential data establishing the scientific foundation for experimental and design parameters to be included in a future Phase III randomized clinical trial, and is the first to examine the molecular effects of long-term LBR administration on at-risk oral mucosa in postsurgical cancer patients and will provide valuable insights related to the modulation of critical genes that might lead to oral cancer prevention.

Lauren Bakaletz, PhDSubinoy Das, MD09/20/02-08/31/13NIH R01R01DC05847Research Institute at Nationwide Chil-dren’s HospitalAntimicrobial Peptides and Innate Immunity in Otitis Media

Due to the continuing need for improved methods to treat and prevent otitis media (OM), the desire for less invasive, more targeted pediatric vaccines, and the realization that our understanding of both the microbiology and immunology of acute and chronic OM is incomplete, it is imperative that we seek a greater understanding of how the body defends the uppermost airway, and that methods to potentially augment these defense mechanisms be identified and developed further as a novel approach for the treat-ment and prevention of OM. Gaining this improved understanding will poten-tially allow us to develop therapeutic approaches that are locally restricted and site-specific, as well as facilitate the re-finement of vaccine formulations so as to enhance their efficacy. These approaches could add tremendously to our available arsenal for fighting acute and chronic OM and, importantly, could potentially provide a mechanism to intervene at a very early state in disease process- colo-nization of the NP, thereby significantly reducing the morbidity associated with this highly prevalent pediatric disease.

Lauren Bakaletz, PhD09/30/99-08/31/09NIH R012R01DC003915-11Research Institute Nationwide Children’s Hospital Determinants of H. Influenzae Virulence in Otitis Media

In 1990, there were 24.5 million physi-cian’s office visits made for middle ear infections [or otitis media (OM)] in The United States alone, representing a more than 200-percent increase over the previous decade. Moreover, worldwide it is reported that between 65 and 330 mil-lion children suffer from chronic secretory OM, 60 percent of which have an associ-ated hearing loss from this disease state, which is characterized by chronically draining ears and can extend over years. The most cost-effective way to manage this highly prevalent pediatric disease, and have a transformational effect on the health of children worldwide, is through the development of novel vaccines to prevent OM, which is the longstanding focus of our research program.

Lauren Bakaletz, PhD7/17/09-10/15/11NIH R012R01DC003915-11Research Institute Nationwide Children’s Hospital Determinants of H. Influenzae Virulence in Otitis Media – Supplement

Lauren Bakaletz, PhDJoann Durbin, MD, PhD01/01/04-12/31/10R01DC006468RSV Upper Airway Infection and Otitis Media

The specific aims are these: 1) Determine whether immunization against RSV can protect against bacterial co-infection in the chinchilla model; 2) Define the cor-relates of upper airway protection; and 3) Determine the mechanisms by which RSV infection enhances host susceptibil-ity of bacterial OM. Recent studies have found that otitis media, or ear infections, in babies and young children are always caused by infection with both a viral and a bacterial organism. The bacteria that cause ear infections normally live in the nose, and are not a problem until the child catches a cold. Once the child has a virus infection, the host defenses are

damaged, and normally harmless bacte-ria then cause disease. There is one cold virus called RSV which infects children over and over and is found in the majority of children with ear infections. Our group has found a new vaccine against this vi-rus, and wants to test whether immunity to RSV can protect against the process that causes bacterial ear infections.

Subinoy Das, MD02/01/09-01/31/2011NIHKL2RR025754Nationwide Children’s Research InstituteImproving Patient Care via Proteomics Based, Microbe-Specific Detection of Chronic Rhinosinusitis

The goals of this project are to 1) iden-tify patients with chronic rhinosinusitis (CRS), specifically due to the presence of NTHI biofilms, utilizing a high throughput proteomics-based assey and 2) test a priori that will predict the development of biomarkers to be used as clinical diagnostic tools to diagnose CSR at very early stages of disease progression and aid in the development of non-surgical therapies for CRS.

Abraham Jacob, MD08/01/09-08/01/14NIH/NCIK08The Ohio State UniversityPreclinical Testing of a Novel PDK1 Inhibitor for Treating Vestibular Schwannoma

Vestibular Schwannomas (VS), brain tumors arising from the balance nerve, are one of the few deadly diseases of the ear, and patients with VS are currently treated with high-risk modalities such as surgery or radiation therapy because no effective drugs are available. This proposal seeks to study OSU-03012, a new drug that may revolutionize the treatment of VS. We plan to better understand how OSU-03012 inhibits VS tumor growth and profile its safety and efficacy parameters in order to transition this drug into human clinical trials.

continued on page 11.

New House Staff OSU Department of Otolaryngology 2010-2011

Otolaryngology PGY-1 Residents

Troy Howard, MD

Sanford School of Medicine of the University of South Dakota

Ph: 605-670-1738 E-mail: [email protected]

• Born in Provo, Utah

• Undergraduate at Brigham Young University in Physiology and Developmental Biology

• Hobbies include fly fishing, scratch golfer, violin (classical and fiddle), skiing, basketball, and speaks Hungarian fluently

Benjamin Tweel, MD

Columbia University College of Physicians and Surgeons

Ph: 917-763-8798 E-mail: [email protected]

• Born in Columbus, Ohio

• Undergraduate at Duke University in Biology

• Has written, recorded and produced five albums of original music: “New Animals,” “There is a Problem with My Tape Recorder,” “Isomers EP,” “I Sat on the Roof,” and “Ceiling Lights from Street.”

• Website and graphic design

• Water Polo Club, Columbia University

Winslow Idicula, MD

Texas Tech University School of Medicine

Ph: 214-680-9624 E-mail: [email protected]

• Born in Dallas

• Alpha Omega Alpha (Member of AOA)

• Undergraduate at Texas Tech University majoring in Biol-ogy and minoring in Chemistry

• Hobbies include sketching, sculpting, painting, hockey, racquetball, football

Leslie Kim, MD

Northwestern University Feinberg School of Medicine

Ph: 516-884-6915 E-mail: [email protected]

• Born in Seoul, South Korea

• Undergraduate at Weinberg College of Arts and Sciences, Northwestern University in Honors Program in Medical Education, Psychology

• Fluent in Korean, conversational in Spanish

• Enjoys traveling, running outdoors and painting

Head and Neck Oncologic Surgery Fellow

Hassan Arshad, MD

Medical School: Wayne State University School of Medicine

Residency: West Virginia University School of Medicine

E-mail: [email protected]

Laryngology Fellow

Ryan Hendricker, MD

Medical School: University of Illinois in Peoria

Residency: The Ohio State University

E-mail: [email protected]

Neurotology, Otology, Cranial Base Surgery Fellow

Matthew Bush, MD

Medical School: Marshall University Joan C. Edwards School of Medicine, Huntington, W. Va.

Residency: Otolaryngology - Head and Neck Surgery, University of Kentucky, Lexington

E-mail: [email protected]

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The Ohio State University Medical Center Department of Otolaryngology page 8

 

Highlight: Quintin Pan, PhDQ

uintin Pan, PhD

The Ohio State University Medical Center Department of Otolaryngology page 9

Quintin Pan, PhD, is associ-ate professor and research director of the Head and Neck Oncology Program in Ohio State’s Department of Oto-laryngology – Head and Neck Surgery. Dr. Pan received his PhD in pharmacology and completed a postdoctoral fellowship in cancer biology at the University of Michigan Medical School. Dr. Pan’s re-

search is focused on understanding the genetic determi-nants of aggressive head and neck cancer. His laboratory is interested in identifying druggable genes and targets, understanding how these genes function in the context of head and neck cancer development and progression, and designing selective inhibitors against these genes as novel anti-cancer therapeutics.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with an annual incidence of approximately 600,000 cases worldwide. Alcohol and tobacco use are the traditional hallmark risk factors for the development of HNSCC. However, the pathogenesis of HNSCC is changing due to the recognition of HPV infection as a major risk factor for HNSCC, in particular tonsil and base of tongue. Epidemiological data indicate that the prevalence of HPV-related HNSCC has rapidly increased by about threefold in the past three decades in the United States and Europe. Based on these alarming numbers, it has been suggested that an epidemic of HPV-positive HNSCC will emerge in the near future.

Patients with HPV-positive HNSCC tend to present to the clinic with more advanced disease due to increased nodal involvement than patients with HPV-negative HNSCC. Paradoxically, there is considerable evidence that HPV-positive HNSCC has higher response and survival rates than HPV-negative HNSCC. Several potential possibilities put forth by clinicians and scientists in the field are that heightened immune surveillance, increased sensitivity to chemotherapy and radiotherapy, and lack of field cancer-ization may be responsible for the favorable prognosis of

HPV-positive HNSCC. Additional research is needed to confirm these suggestions and to explore other mecha-nisms to explain the superior response and prognosis of HPV-positive HNSCC

Pan and colleagues recently discovered a profound differ-ence in the cancer stem cell (CSC) population between HPV-negative and HPV-positive HNSCC. CSCs are a small subset of cancer cells within the tumor with the exclusive capacity to divide and expand the CSC pool or to differentiate into heterogeneous non-tumorigenic cells that constitute the bulk of the tumor. There is emerg-ing evidence that CSCs are refractory to chemotherapy and radiation, suggesting that CSCs may be responsible for disease relapse and progression. Pan and colleagues demonstrated that HPV-positive HNSCC have elevated CSC numbers, possibly through enhance self-renewal, providing an explanation for the increased nodal involve-ment of HPV-positive HNSCC at time of presentation and moreover, CSCs from HPV-positive HNSCC are exqui-sitely sensitive to cis-platinum, providing an explanation for the superior prognosis of HPV-positive HNSCC. These provocative results indicate that HPV alters CSC pheno-type and provides an innovative mechanism to explain the divergent clinical response between HPV-positive and HPV-negative HNSCC.

Ongoing research in the Pan laboratory is exploring two clinically relevant and significant questions in HNSCC:

• Why does HPV-positive HNSCC respond better to treatment than HPV-negative HNSCC?

• How do we alter HPV-negative HNSCC to respond similarly to HPV-positive HNSCC?

Understanding the CSC biology of HPV-positive HNSCC will provide the insight required to advance the develop-ment of novel therapeutic strategies to target HPV-posi-tive and HPV-negative HNSCC.

Publications for 2009/2010

Jatana KR, Balasubraman P, Lang JC, Yang L, Jatana CA, White E, Schuller DE, Agrawal A, Ozer E, Teknos TN, Chalmers JJ. Sig-nificance of circulating tumor cells in patients with squamous cell carcinoma of the head and neck: Initial results. Arch Otolaryn Head Neck Surg, 2010;136(12):1-6.

Prior S, Heaton J, Jatana KR, Rashid RG. Parker Flex-Tip and Standard-Tip endotracheal tubes: A comparison during nasotra-cheal intubation. Anesthesia Progress, 2010;57(1):18-24.

McGillivary G, Bakaletz LO. The multifunctional host defense peptide SPLUNC1 is critical for homeostasis of the mammalian upper airway. PLoS One. 2010 Oct 7;5(10):e13224. PubMed PMID: 20949060; PubMed Central PMCID: PMC2951362.

Grieves JL, Jurcisek JA, Quist B, Durbin RK, Peeples ME, Durbin JE, Bakaletz LO. Mapping the anatomy of respiratory syncytial virus infection of the upper airways in chinchillas (Chinchilla lanigera). Comp Med. 2010;60(3):225-32. PubMed PMID: 20579438; PubMed Central PMCID: PMC2890398.

Bowe SN, Jacob A. Round window perfusion dynamics: implica-tions for intracochlear therapy. Curr Opin Otolaryngol Head Neck Surg. 2010 Oct;18(5):377-85. PubMed PMID: 20808222.

Contag SP, Golub JS, Teknos TN, Nussenbaum B, Stack BC Jr, Arnold DJ, Johns MM 3rd. Professional Burnout Among Micro-vascular and Reconstructive Free-Flap Head and Neck Surgeons in the United States. Arch Otolaryngol Head Neck Surg. 2010 Aug 16. [Epub ahead of print] PubMed PMID: 20713750.

Kumar P, Yadav A, Patel SN, Islam M, Pan Q, Merajver SD, Teknos TN. Tetrathiomolybdate inhibits head and neck can-cer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis. Mol Cancer. 2010 Aug 3;9:206. PubMed PMID: 20682068; PubMed Central PMCID: PMC2922193.

Bush ML, Pritchett C, Packer M, Ray-Chaudhury A, Jacob A. Hemangioblastoma of the cerebellopontine angle. Arch Otolaryngol Head Neck Surg. 2010 Jul;136(7):734-8. PubMed PMID: 20644074.

Yates CW, Weinberg M, Packer MJ, Jacob A. Fatal case of tumor-associated hemorrhage in a large vestibular schwannoma. Ann Otol Rhinol Laryngol. 2010 Jun;119(6):402-5. PubMed PMID: 20583739.

Wan D, Wiet GJ, Welling DB, Kerwin T, Stredney D. Creating a cross-institutional grading scale for temporal bone dissection. Laryngoscope. 2010 Jul;120(7):1422-7. PubMed PMID: 20564671.

Calhoun KH, Schofield ML. IgE-mediated food allergy. Curr Opin Otolaryngol Head Neck Surg. 2010 Jun;18(3):182-6. PubMed PMID: 20463481.

Nittrouer S, Lowenstein JH. Learning to perceptually orga-nize speech signals in native fashion. J Acoust Soc Am. 2010 Mar;127(3):1624-35. PubMed PMID: 20329861; PubMed Central PMCID: PMC2856515.

Hendricker RM, deSilva BW, Forrest LA. Gore-Tex medialization laryngoplasty for treatment of dysphagia. Otolaryngol Head Neck Surg. 2010 Apr;142(4):536-9. PubMed PMID: 20304274.

Jatana KR, Oplatek A, Stein M, Phillips G, Kang DR, Elmaraghy CA. Effects of nasal continuous positive airway pressure and cannula use in the neonatal intensive care unit setting. Arch Otolaryngol Head Neck Surg. 2010 Mar;136(3):287-91. PubMed PMID: 20231649.

Ozer E, Karapinar U, Ryoo C, Agrawal A, Schuller DE. When to ad-dress level I lymph nodes in neck dissections? Otolaryngol Head Neck Surg. 2010 Mar;142(3):355-8. PubMed PMID: 20172380.

Ozer E, Bapna S, Agrawal A, Schuller DE. Maxillary removal and reinsertion: a favorable approach for extensive ante-rior cranial base tumors. Otolaryngol Head Neck Surg. 2010 Mar;142(3):322-6. Epub 2010 Jan 22. PubMed PMID: 20172374.

Leung R, Samy RN, Leach JL, Murugappan S, Stredney D, Wiet G. Radiographic anatomy of the infracochlear approach to the petrous apex for computer-assisted surgery. Otol Neurotol. 2010 Apr;31(3):419-23. PubMed PMID: 20084044.

Tong HH, Li YX, Stahl GL, Thurman JM. Enhanced suscepti-bility to acute pneumococcal otitis media in mice deficient in complement C1qa, factor B, and factor B/C2. Infect Immun. 2010 Mar;78(3):976-83. Epub 2010 Jan 11. PubMed PMID: 20065024; PubMed Central PMCID: PMC2825922.

Pan Q, Rosenthal DT, Bao L, Kleer CG, Merajver SD. Antiangiogenic tetrathiomolybdate protects against Her2/neu-induced breast carcinoma by hypoplastic remodeling of the mammary gland. Clin Cancer Res. 2009 Dec 1;15(23):7441-6. Epub 2009 Nov 24. PubMed PMID: 19934283.

Oplatek A, Ozer E, Agrawal A, Bapna S, Schuller DE. Patterns of recurrence and survival of head and neck adenoid cystic carcino-ma after definitive resection. Laryngoscope. 2010 Jan;120(1):65-70. PubMed PMID: 19877226.

Shahin AJ, Trainor LJ, Roberts LE, Backer KC, Miller LM. Development of auditory phase-locked activity for music sounds. J Neurophysiol. 2010 Jan;103(1):218-29. Epub 2009 Oct 28. PubMed PMID: 19864443; PubMed Central PMCID: PMC2807221.

Kraut EH, Rhoades C, Zhang Y, Cheng H, Aimiumu J, Chen P, Lang J, Young DC, Agrawal A, Dancey J, Chan KK, Grever MR. Phase I and pharmacokinetic study of erlotinib (OSI-774) in com-bination with docetaxel in squamous cell carcinoma of the head and neck (SSCHN). Cancer Chemother Pharmacol. 2010 May 19. [Epub ahead of print] PubMed PMID: 20490801.

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The Ohio State University Medical Center Department of Otolaryngology page 10 The Ohio State University Medical Center Department of Otolaryngology page 11

Publications for 2009/2010

The Ohio State University Medical Center Department of Otolaryngology page 11

Marler JA, Sitcovsky JL, Mervis CB, Kistler DJ, Wightman FL. Auditory function and hearing loss in children and adults with Williams syndrome: cochlear impairment in individuals with otherwise normal hearing. Am J Med Genet C Semin Med Genet. 2010 May 15;154C(2):249-65. PubMed PMID: 20425785; PubMed Central PMCID: PMC2913545.

Watts CR, Marler JA, Rousseau B. Qualitative Characterization of Elastic Fiber Distribution in the Mouse Vocal Fold: Further De-velopment of an Animal Model. J Voice. 2010 Feb 3. [Epub ahead of print] PubMed PMID: 20137895.

Kerlin JR, Shahin AJ, Miller LM. Attentional gain control of ongoing cortical speech representations in a “cocktail party”. J Neurosci. 2010 Jan 13;30(2):620-8. PubMed PMID: 20071526; PubMed Central PMCID: PMC2832933.

Backer KC, Hill KT, Shahin AJ, Miller LM. Neural time course of echo suppression in humans. J Neurosci. 2010 Feb 3;30(5):1905-13. PubMed PMID: 20130199; PubMed Central PMCID: PMC2835501.

Bomjun Kwon, PhD12/01/08-11/30/11NIH/NIDCRR03DC009061The Ohio State UniversityPerceptual Effects of Mixed Channel Configurations in Cochlear Implants The proposed study examines how deaf patients who have received cochlear implants percep-tually organize one sound or multiple sounds with the electrical currents from the device. By investigating a new method of construct-ing current channels in a cochlear implant system that facilitates a good hearing and understanding of sounds, more benefits from the device will be expected in the future.

Susan Nittrouer, PhD09/01/88-11/30/10NIH/NIDCDR01DC000633The Ohio State UniversityOntogeny of Segmental Speech Organization

The goal of this project is to investigate how children acquire access to segmental structure in the speech signal which largely lacks any explicit acoustic structure.

Susan Nittrouer, PhD9/1/03-2/28/15NIH/NIDCDR01DC006237The Ohio State UniversityEarly Development of Children with Hearing Loss

The goal of this project is to investigate outcomes for children with hearing loss as a function of age of identification, whether signs were used in early intervention or not and type of prosthesis.

Matthew Old, MD06/01/2010-05/31/2010NCRR/NIHUL1RR025755 The Ohio State University

OSU Center for Clinical and Translational Science (CCTS) and Richard P. and Marie R. Bremer Medical Research Fund (Davis/Bremer Research Fund) Novel Oncolytic Virus Therapy in Squamous Cell Carcinoma

Quintin Pan, PhD07/01/08-05/31/13NIH/ROI ROICA135069The Ohio State UniversityRole of PKCepsilon in Oral Cancer

The goal of this project is to study the bio-logical role of PKCepsilon in the develop-ment of metastasis, a recalcitrant chal-lenge in oral squamous cell carcinoma.

Antoine Shahin, PhD07/01/10-6/30/13R03The Ohio State UniversityThe Development of Electrophysiological Auditory Response for Speech

The proposed research will help expand our current knowledge of auditory cortex development in normal-hearing children. We will identify specific brain activity as-sociated with the development of specific speech properties. In the future, we will use the knowledge obtained from this research to assess auditory development in children with speech and language deficits.

Hua Hua Tong, MD07/01/08-06/30/12NIH R01R01DC003235The Ohio State University Complement in S. Pneumoniae Otitis Media

The specific aims are to: 1. Assess the complement activation in the middle ear epithelium during Spn infection. 2. Define the role of the specific complement pathways in the middle ear defense against Spn using

a complement deficient mouse model. 3. Evaluate the role of complement C3 in the middle ear against Spn with an antecedent influenza A virus infection in the chinchilla model of OM, and to examine the relevance of alteration of Spn gene expression in vivo to complement resistance of Spn. Otitis media (middle ear inflammation) is one of the most common childhood diseases. The prevalence, medical costs, and hearing-related morbidity of otitis media (OM) are significant. This ap-plication is designed to study the critical role of complement in middle ear defense against Streptococcus pneumoniae (Spn) bacteria, the primary pathogen of middle ear infec-tion to better understand the host immune response to this pathogen.

D. Bradley Welling, MD, PhD05/10/05-04/30/10NIH R01R01DC005985The Ohio State UniversityPhenotypic Determinants of Vestibular Schwannomas

The goal of this project is to explore the critical role of regulatory regions in the NF2 gene in schwannomas and further identify and understand factors which affect phenotypic expression in vestibular schwannomas.

D. Bradley Welling, MD, PhD06/01/09-05/31/10NIH R01R01DC005985The Ohio State UniversityPhenotypic Determinants of Vestibular Schwannomas – Supplement

The goal of this project is to explore the critical role of regulatory regions in the NF2 gene in schwannomas and further identify and understand factors which affect phenotypic expression in vestibular schwannomas.

NIH Research Funding cont. from pg. 7

In 2007, Dr. Susan Nittrouer joined our faculty and is conduct-ing research on this question. Just this year, she was re-fund-ed by the National Institute on Deafness and Other Com-munication Disorders to continue a large longitudinal study with more than 200 children from across the country. As part of this effort, she and her team will fly 60 deaf children and their parents to Columbus, Ohio, this summer to participate in two-day “data camps.” Information will be gathered at these camps concerning children’s language development, as well as their behavior, psychosocial and cognitive development, academic performance and parental stress.

Along with collecting data that will help clinicians modify the way that early intervention is delivered to these children and their families, these camps provide opportunities for residents in the Department of Otolaryngology and graduate students in Speech and Hearing Science, Psychology and Linguistics to learn about the speech, language and cognitive abilities of deaf children and gain experience interacting with them.

Summer Data Camps for Deaf Children continued from page 4

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