8MANDIBULAR DISTRACTION. Otolaryngology Advances. Therapeutic Vaccine Development for SCC Continues on Path of Progress

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1 Fa l l B R I D G I N G R E S E A R C H A N D C L I N I C A L C A R E Otolaryngology Advances A Physician Newsletter from The Cleveland Clinic Therapeutic Vaccine Development for SCC Continues on Path of Progress Up to 95% of all head and neck tumors are squamous cell carcinomas (SCC). Despite recent advances in surgery, radiation and chemotherapy, the long-term prognosis for patients with advanced SCC of the head and neck continues to be poor because the five-year risk for dying from distant metastases has remained unchanged in the past 30 to 40 years. Researchers at The Cleveland Clinic Head and Neck Institute hope to improve that situation with the development of an effective therapeutic vaccine. The vaccine would be used as an adjunct to existing treatment modalities for preventing progression in patients at high risk for metastasis after treatment of their primary tumor, or to treat people with existing disseminated disease. The project, led by Research Director Suyu Shu, Ph.D., takes a novel approach to creating a dendritic cell-based vaccine by implementing electrofusion to form a hybrid from dendritic cells and whole tumor cells that are derived from banked cell lines. The electrofusion technique has been used successfully in other disciplines to achieve cell fusion. Dr. Shu has been able to achieve very efficient fusion rates, and results from series of experiments using animal and human tumor cell lines demonstrate success in producing fused cells that both display the phenotype of the mature dendritic cell and express tumorassociated antigens. 3 contents 2Spoken Language Rehabilitation Services Offered through Hearing Implant Program Cell fusion to produce dendritic cell vaccines has also been attempted using chemical or viral fusogens. However, those methods are much less efficient than what we have been able to achieve using this electrofusion technique, says Dr. Shu. However, the use of the whole tumor cells is another important aspect of the immunotherapy approach being developed because the fused cells bear a diverse array of unaltered tumor antigens. The researchers hope that feature, combined with the capability of the dendritic cells to convey a powerful stimulatory signal to T cells, will result in a vaccine that is very effective in eliciting therapeutic host immune responses and therefore in destroying existing cancer cells. While there may be interindividual heterogeneity in tumor antigens, there is good evidence for the presence of shared antigens among SCCs derived from different patients. Use of whole tumor cells eliminates the need to spend time identifying individual antigens and has the advantage of creating a vaccine that will present both SUCCESS OF NOVEL IMMUNOSUPPRESSIVE REGIMEN PROMISING FOR LARYNGEAL TRANSPLANT known and yet-unknown antigens to the immune system, explains Dr. Shu. Animal studies completed so far have provided encouraging results about the activity of the vaccine. In various experiments using vaccines created with autologous dendritic cells and either melanoma or fibrosarcoma cell lines, the vaccine has demonstrated efficacy in preventing tumor development in animals that received postvaccination challenge with tumor cells as well as for causing regression of tumors allowed to become established in the lung, brain and skin. Importantly, the anti-tumor effects of these vaccines also translated into a benefit for prolonging survival, says Walter Lee, M.D., Cleveland Clinic Head and Neck Institute Research Fellow. The therapeutic vaccine is expected to have a good safety profile, relative to chemotherapy or radiation. Dr. Shu and his team are now focusing on developing vaccines for clinical use. After receiving IRB approval, they have begun growing human SCC cell lines and have achieved success fusing human dendritic cells with human melanoma cells. Evaluations of the ability of those hybrids to present tumor-associated epitopes and induce cytokine secretion from T-cells confirm that the fusion technique could be successfully translated to the use of human material to produce immunocompetent cells, Dr. Lee reports. 8MANDIBULAR DISTRACTION OSTEOGENESIS IN NEONATES useful in pierre robin sequence

2 Spoken Language Rehabilitation Services Offered through Hearing Implant Program A new program offers expanded care to patients with implantable hearing devices The new Cleveland Clinic Hearing Implant Program (HIP) will serve patients with hearing loss of all types, but will especially focus on surgical methods of restoring hearing using cochlear implants, boneanchored hearing appliances (BAHA) or middle ear implants. It will be located at the Cleveland Clinic Health System s Hillcrest Hospital. Otolaryngologist Peter C. Weber, M.D., who has served as Director of Implantable Hearing Devices at the Clinic, will co-direct the new program with Donald M. Goldberg, Ph.D., who has joined the staff. Dr. Goldberg is a speech-language pathologist and audiologist, and with his expertise, the new program will be able to provide implant recipients the important benefit of spoken language rehabilitation services. The offering of speech and language rehabilitation in addition to care from dedicated audiologists will make our program unique in the Eastern Great Lakes region and therefore, we believe, the top cochlear implant program in this area, says Dr. Weber. The Cleveland Clinic Head and Neck Institute has always featured an excellent team of otolaryngologists and audiologists and my goal is to add to the existing services such that the new facility becomes a leading referral center in the nation, Dr. Goldberg says. Follow-up for patients who receive implantable hearing devices often focuses strictly on programming the sound processor. However, once a person regains or newly acquires the physiologic ability to hear, proper training is critical for optimizing use of that sense. One of my roles is to provide the necessary rehabilitation that will move patients through the hierarchy from mere sound detection to the level of comprehension, thereby enabling them to use their newly stimulated hearing in a way that they are listening for life, Dr. Goldberg says. In addition to offering more comprehensive care, with more space and a larger staff, the new program will be able to expand its current clinical, educational and research efforts. In 2004, Dr. Weber, together with colleagues Gordon B. Hughes, M.D., and Keiko Hirose, M.D., performed about 80 cochlear implant procedures and approximately 25 BAHA operations on patients ranging from 1 to nearly 90 years old. Dr. Weber expects the number of procedures to double. Our department has already been on the cutting edge for many research opportunities with new devices, but our new auditory learning program should make us an even more attractive investigational site for industry sponsors, Dr. Weber says. Outreach will be expanded to improve awareness of opportunities for treating hearing loss among health care professionals and the public. Patients with hearing problems are underserved due to a lack of appreciation for the expanded criteria for implantable device candidacy. In the past, only people who could not hear anything were considered eligible for cochlear or bone-anchored implants. Today, however, there is an appreciably sized population of individuals who have some residual hearing, who are not being helped with conventional hearing aids and who could benefit from an implantable device, Dr. Weber says. We hope to shed more light on the opportunities available so that patients are no longer unnecessarily living in silence, he adds. Appointments in the new program can be scheduled at 440/ (312-ENT1). From the Chairman Dear Colleague: This issue of Otolaryngology Advances again highlights cutting-edge medical and surgical progress. Growth requires the appropriate infrastructure and, this year, our new Hearing Implant Program and pediatric suites will open. The implant program, co-directed by Peter Weber, M.D., and Donald Goldberg, Ph.D., will be housed in a state-of-the-art 3,500-square-foot suite. Our bone-anchored hearing appliance program continues to grow and this year we expect to perform 100 cochlear implants. We anticipate that the excellence of the unit will make us even more competitive for external funding. Our long-awaited pediatric suite has a separate waiting area and exam rooms to accommodate our growing pediatric volume on the main campus. We await the arrival of our recently recruited third pediatric otolaryngologist in July 2006 and anticipate a fourth position in July Inevitably, in an academic environment, goals and lives change. This year, Peter Koltai, M.D., and Donald Lanza, M.D., for personal considerations, left the Institute. They were more than colleagues and are missed. Keiko Hirose, M.D., became Section Head of Pediatrics and Martin Citardi, M.D., became Section Head of Rhinology. Both are exceptional clinician-scientists and have already had a significant impact in their new roles. As Ray Esclamado, M.D., assumed more roles as Vice Chair of the Institute, he suggested that Rob Lorenz, M.D., be elevated to lead the Head and Neck Section, and Rob is thriving in his new role. We received approval from our IRB to initiate our parathyroid transplant program under Rob Lorenz s direction. Further, I expect to perform our second laryngeal transplantation later this year. We also will initiate our robotic surgery program and hope to expand its head and neck applications. I hope you enjoy this edition of Otolaryngology Advances. Sincerely, Marshall Strome, M.D., M.S., F.A.C.S. 2 Head and Neck Institute

3 Success of Novel Immunosuppressive Regimen Holds Promise for Expansion of Laryngeal Transplantation Study Achieves 100 Percent Graft Survival at Six Months In 1998, Marshall Strome, M.D., M.S., F.A.C.S., Chairman of The Cleveland Clinic Head and Neck Institute, in collaboration with a team of Cleveland Clinic physicians, performed the first total larynx transplant. While that surgery can confer recipients with multiple quality-of-life benefits, its more widespread performance has been limited by the necessity for lifelong immunosuppressive therapy and its associated risks. To address the latter obstacle, Cleveland Clinic researchers designed a study using a rat model of laryngeal transplantation to evaluate various approaches for minimizing immunosuppression. The research team, headed by Dr. Strome, has yielded encouraging results regarding the efficacy of a novel, short-course, intermittent regimen for preventing graft rejection. Resident Samir Khariwala, M.D., conducted the research, and with colleagues recently reported achieving 100% graft survival after six months in animals treated for a total of only 12 days with the combination of everolimus (SDZ-RAD) plus an alphabeta-t-cell receptor monoclonal antibody. Laryngectomy carries a huge negative social stigma and can have a devastating impact on quality of life. Laryngeal transplantation can be life-altering by permitting more normal speech, eating and breathing. However, its benefits need to be weighed carefully, considering that the larynx is a non-vital organ and that the immunosuppression needed to maintain the graft is associated with myriad risks, Dr. Khariwala says. The ability to minimize immunosuppression without compromising graft survival should allow more patients to become candidates for laryngeal transplantation, he adds. In his study, 15 animals were divided into three groups. All received everolimus 5 mg/kg/day plus the T-cell depleting antibody for an initial seven-day course at the time of transplantation and for a second five-day course 90 days later. One group received no additional therapy while the other two groups received continuous maintenance treatment with everolimus 1 or 2.5 mg/kg/day. All of the animals survived until being killed at 180 days, and histological evaluation of the transplanted larynges indicated 100% functional allograft tolerance. The key finding in this study was the efficacy of the pulsed immunosuppression regimen for maintaining graft survival. However, the finding that ongoing, low-dose everolimus monotherapy was effective is also significant because it suggests this safer alternative to current aggressive multidrug regimens might be useful for managing patients at increased risk of graft rejection, Dr. Khariwala says. The efficacy achieved using everolimus is also notable because that drug has been shown to have antitumor properties in addition to its immunosuppressive activity. The antitumor Samir Khariwala, M.D., (at left) and Marshall Strome, M.D., M.S., F.A.C.S., study how to minimize immunosuppression in laryngeal transplants. effects of everolimus are relevant to all transplant patients because immunosuppressive therapy is associated with an increased risk of developing skin cancer and other types of malignancies. However, it has added importance in the setting of laryngeal transplantation because cancer treatment is the most common indication for laryngectomy, Dr. Khariwala points out. Immunosuppressive therapy in patients with a history of cancer poses the added risk of increasing the likelihood of recurrence. With its dual immunosuppressive and antitumor activities, everolimus is an attractive choice for managing patients who have undergone laryngectomy and laryngeal transplantation because of cancer, he explains. Future research seeks to elucidate the underlying mechanisms for the prolonged efficacy of the short-course immunosuppressive treatment. In addition, the investigators are evaluating alternative approaches for achieving the ultimate goal of inducing allograft tolerance, such as with the use of donor bone marrow cells or dendritic cells. Dr. Khariwala was honored in May as the recipient of the American Laryngological Association s annual Resident Research Award. Head and Neck Institute 3

4 Landmark Research Identifies Inflammatory Response to Inner Ear Injury May Open Door to New Approaches to Hearing Loss Treatment A better understanding of the signals for inflammatory cell migration and activation will provide us with better insight into selecting therapeutic targets, Keiko Hirose, M.D., says. Keiko Hirose, M.D., at work in her laboratory at The Cleveland Clinic Head and Neck Institute. Cleveland Clinic researchers studying the cellular and molecular mechanisms underlying hearing degeneration have demonstrated that the inner ear exhibits a marked inflammatory response to direct tissue injury induced by noise. This discovery not only refutes existing dogma that the inner ear is relatively resistant to inflammation, but may point to new opportunities for treating hearing loss, says Keiko Hirose, M.D. Dr. Hirose, of The Head and Neck Institute, and members of her laboratory examined the cochlea for evidence of inflammation after acoustic injury. They found few inflammatory cells in tissue from control animals not exposed to noise, whereas in animals subjected to noise overexposure, there was a large increase in bone-marrow-derived white blood cells in the cochlea within days after the insult. The inflammatory cells were concentrated in the spiral ligament and spiral limbus, sites known to manifest cellular loss following noise trauma and in association with age-related hearing degeneration. This discovery of an exuberant inflammatory response in the cochlea is a novel finding and is in contradiction to current concepts that the ear is very similar to the anterior chamber of the eye with respect to being immunologically quiescent, says Dr. Hirose. Although it is not known whether the inflammatory reaction to acoustic injury propagates cellular damage or plays a role in promoting cellular repair, the finding that these inflammatory cells can enter the ear very easily is important because we can expect they may be primary mediators of injury leading to hearing loss in some pathological conditions. Immunostaining studies to characterize the population of migrating cells indicated they appeared to be from monocyte-macrophage lineage, and therefore would be expected to have a phagocytic function. She suggests that in other disease processes Institute Achieves High Rank involving the ear, an inflammatory cell population might have a more active causal role in producing hearing loss. If inflammation plays a critical role in certain types of hearing loss, we may be able to intervene with agents that modulate the inflammatory response and prevent or perhaps even restore hearing, she says. In researching the basic pathophysiologic mechanisms of hearing loss, Dr. Hirose and colleagues began studying noise as an insult because it is simple to replicate and is welltolerated by the animals while still allowing investigators to evaluate the key question of what cellular events occur in the inner ear after injury. Now, they are focusing on characterizing the basic pathways leading to hearing loss in more detail by looking at the specific events that lead to influx of the inflammatory cells in order to acquire clues about potential interventions. A better understanding of the signals for inflammatory cell migration and activation will provide us with better insight into selecting therapeutic targets, Dr. Hirose says. Dr. Hirose s findings were published in the Journal of Comparative Neurology (J Comp Neurol Aug 22;489(2):180-94). The Cleveland Clinic Head and Neck Institute is ranked among the most highly rated ear, nose and throat programs in the United States by U.S.News & World Report. The Cleveland Clinic continues to be recognized as one of America s Best Hospitals in the magazine s annual survey. In 2005, The Cleveland Clinic was ranked the nation s fourth best hospital. 4 Head and Neck Institute

5 Resolution of Vestibular Disorders Now More Easily Achieved with In-Office Procedures Rapid advances in the evaluation and management of vestibular disorders allow the majority of people suffering with dizziness and vertigo to achieve resolution. At The Cleveland Clinic Head and Neck Institute, Judith A. White, M.D., Ph.D., and members of a multidisciplinary team have been on the forefront in evaluating and implementing new approaches to the diagnosis and treatment of dizziness and imbalance. For benign paroxysmal positional vertigo (BPPV), one of the most common vestibular disorders, the focus is on use of in-office, non-invasive techniques. Patients with BPPV present with a specific type of nystagmus, depending on which semicircular canal is involved. Using Fresnel lenses to eliminate visual fixation, it is possible to characterize the nystagmus accurately, determine the type of BPPV and select the appropriate approach to treatment, Dr. White explains. Now, most of our diagnostic decisions can be made in a brief, well-tolerated office evaluation rather than routinely subjecting patients to time-consuming, detailed vestibular testing in the laboratory, she says. Recent developments in the understanding of BPPV pathophysiology have led to the use of new, highly effective approaches to intervention using various repositioning maneuvers. For patients with posterior canal BPPV, which accounts for 95% of BPPV cases, results of a recently published meta-analysis performed by Dr. White highlight the efficacy of using repositioning maneuvers popularized by Epley and Semont. According to the findings of that study, 80% of patients can be treated successfully with a single session. An ongoing clinical trial is evaluating whether postural control after the repositioning maneuver influences success. That IRB-approved, double-blind trial is randomly assigning 110 patients who are successfully treated with in-office repositioning using the Epley maneuver to careful postural restriction or simply receiving information on BPPV and its associated fall risk. Patients will return after one week for assessment of BPPV recurrence. Several European studies suggest that postural restriction after canalith repositioning with the Semont maneuver had no impact on outcomes. However, a number of centers continue to recommend postural restriction. We are using a slightly different maneuver for repositioning, and with our study s controlled design and large sample size, we should be able to determine conclusively whether its outcome is affected by postural control, she says. The interaction of the vestibular and visual system is evaluated during vestibular testing by Judith A.White, M.D., Ph.D., to determine the cause of disequilibrium. Dr. White s research also has determined effective treatment for horizontal canal conversion, an event that occurs in up to 15% of patients after treatment for posterior canal BPPV. After the repositioning maneuvers are completed, patients are placed back into the provocative Dix Halpike position and observed for residual nystagmus. The onset of a violent horizontal nystagmus, which is perceived subjectively by patients as being different from their prior type of dizziness, signifies the particle has fallen into the horizontal canalith. Our studies show that this conversion can be easily managed by placing patients supine and rolling them 360 in the direction of the uninvolved ear, she explains. For more challenging cases in which the diagnosis is questionable or to evaluate patients whose condition is refractory to routine positioning maneuvers, two state-of-the-art computer infrared laboratories are available. In addition, Dr. White and her colleagues are exploring more complex diagnostic challenges in patients with persistent lightheadedness or disequilibrium not accounted for by BPPV. Patients are also seen who have migraine-associated dizziness and persistent lightheadedness after a vestibular problem related to problems with postural blood pressure control. The 2005 Vestibular Update, for physicians and other medical professionals, will be Nov at The Cleveland Clinic. For information, call Karen Margosian at 216/ or visit Head and Neck Institute 5

6 Large Patient Cohort Provides Foundation for Understanding Optimal ENT Management Wegener s granulomatosis is such an exceedingly rare autoimmune disorder that the average otolaryngologist might expect to treat no more than a handful of patients with ear, nose and throat manifestations of this condition in his or her career. However, at The Cleveland Clinic s Head and Neck Institute, Robert Lorenz, M.D., Section Head of Head and Neck Surgery, is currently taking care of more than 200 patients with Wegener s granulomatosis. That large cohort offers a rich resource treated about 45 patients for subglottic stenosis and have performed about 90 operations on them over the past 10 years. In our experience, the average patient requires about 2.5 dilations before going into remission, and no patient in whom patients with Wegener s granulomatosis have some amount of sinonasal disease, and so we are further evaluating relationships involving the extent of disease, the presence of active infection and the quiescence of systemic problems, Dr. Lorenz says. We focus on symptomatic management, avoiding more aggressive therapies that, while intended to be curative, in fact can be harmful, Robert Lorenz, M.D., says. Figure 1: Radiograph showing the stenosis. Figure 2: Stenosis is seen. for an active program of outcomes research, and follow-up of that group has provided a number of important insights regarding optimal intervention. Clinical experience with this group supports the Clinic s minimalist approach to the surgical management of the upper airway manifestations of Wegener s granulomatosis, Dr. Lorenz says. We focus on symptomatic management, avoiding more aggressive therapies that, while intended to be curative, in fact can be harmful, he comments. For example, daily nasal hygiene with saline douches and topical antibiotics is the mainstay for managing disease involving the nasal cavity, while endoscopic sinus surgery is performed only to prevent complications from sinusitis. Treatment of subglottic stenosis incorporates direct corticosteroid injection, topical application of mitomycin-c and use of a knife, never the CO 2 laser, for performing dilation during microscopic laryngoscopy. The efficacy of our approach is demonstrated by our outcomes. We have we initiated therapy in the larynx has ever gone on to need a tracheostomy, Dr. Lorenz says. A more formal retrospective study demonstrated the safety of using jet ventilation in patients with Wegener s granulomatosis and subglottic stenosis. Comparing those patients against unaffected controls treated with jet ventilation showed there was no difference in rates of tension pneumothorax between the two groups. These results dispel historical concern that patients with Wegener s may be at increased risk for experiencing pneumothorax after jet ventilation, Dr. Lorenz says. Two ongoing studies are investigating a contributory role of Staphylococcus aureus infection in upper airway and systemic manifestations of Wegener s granulomatosis. Our experience suggests treatment with antibiotics can reduce airway inflammation, and interestingly, patients whose disease is resistant to surgical therapy may have concurrent staphylococcal infections, Dr. Lorenz says. Our experience is that almost all Another project focuses on optimal treatment strategies. The extent of sinonasal disease involvement in patients with Wegener s granulomatosis will first be characterized based on findings from CT scans, cultures and endoscopic examination. Definition of what constitutes severe sinonasal involvement versus moderate or mild involvement and how the severity is influenced by bacterial infection will provide a basis for future studies to evaluate optimal treatment strategies and to examine our belief that surgical therapy is not indicated in these patients unless they have impending complications from sinusitis, Dr. Lorenz says. Several of these research projects are ancillary studies to clinical trials being conducted by the Vasculitis Center at The Cleveland Clinic. The Vasculitis Center, together with centers at Boston University, John Hopkins University and The Mayo Clinic, make up the Vasculitis Clinical Research Consortium (VCRC) established with a multimillion dollar National Institutes of Health grant. 6 Head and Neck Institute

7 Cheeklift Offers Minimally Invasive Rejuvenation for Midface Aging Ptotic changes in the midface, including the appearance of drooping cheeks, nasolabial creases, labiomental folds and infraorbital hollows, are among the earliest manifestations of facial aging. They are all caused by gravity-induced descent of the malar fat pad, and none are adequately addressed by traditional facelift surgery that leaves the malar fat pad untouched. Figure 1 Figure 2 Figure 3 At The Cleveland Clinic Head and Neck Institute, Daniel Alam, M.D., Head of the Section of Facial Aesthetic and Reconstructive Surgery, is performing a minimally invasive procedure that is specifically designed to target the signs of midface aging. In this cheeklift operation, he creates a percutaneously placed suspension system using two Prolene sutures to lift the malar fat pads. The procedure can be performed using only local anesthesia or with mild sedation, and his experience with hundreds of patients shows that it effectively rejuvenates the midface to a natural, youthful appearance with minimal risk or morbidity. Dr. Alam collaborated in the development of this cheeklift procedure when he was a facial plastic surgery fellow. It is performed by first creating the exit point for the sutures a 2-cm incision in the hairbearing scalp and lifting a small pocket underneath. Then, two minute punctures are made on the cheek, and a small pledget of biocompatible Alloderm is placed on the fat pad to serve as an anchor for securing the suture. Working first through one puncture site and then the other, the cheek is entered with a long needle that is used to thread the suture material through the malar fat pad and up to the hairline. Once the sutures are in place, the fat pad height is adjusted by pulling on them at their exit point. After the desired position is achieved, the suture ends are fixed to the temporal fascia. The malar fat pad can also be lifted through an operation in which it is reached via the posterior approach under endoscopic dissection that begins at the hairline and traverses all the way over the zygomatic arch. However, that extensive dissection carries a risk of injury to a number of branches of the facial nerve. This minimally invasive cheeklift provides a safer and highly effective solution to what has been one of the most difficult problems in aesthetic facial rejuvenation, Dr. Alam says. The cheeklift procedure can be performed as a stand-alone operation, and as such it is an excellent choice for patients in their late 30s or early 40s who present with midface ptosis but without more advanced facial changes that would necessitate more extensive cosmetic surgery. However, the cheeklift is also a useful adjunct to traditional facelift surgery and can be used to enhance the appearance of patients who have already had a traditional facelift. A traditional facelift stretches the lateral face and neck, but by leaving the midface untouched, it can result in an asymmetric pulled appearance. Adding the cheeklift results in a much more natural, refreshed look overall, Dr. Alam says. In addition to its favorable safety profile, the cheeklift Dr. Alam performs has the advantages of being adjustable and reversible. With this procedure, there is the opportunity to fine-tune the results by simply opening the hairline incision to access the suture. On the other hand, if the patient is totally displeased with the result, it is also possible to cut and remove the suture. When that is done, the tissues fall back to where they were before surgery. Reversibility is certainly not an option for traditional facelift surgery, he says. Head and Neck Institute 7

8 Mandibular Distraction Mandibular hypoplasia in infants born with Pierre Robin sequence leads to glossoptosis and airway obstruction. While most of these children can be managed with conservative measures based on positioning strategies or using temporary nasopharyngeal airways, surgical intervention with tracheostomy has been performed traditionally to manage select cases where there is severe airway compromise. At The Cleveland Clinic Head and Neck Institute, Michael A. Fritz, M.D., advocates mandibular distraction osteogenesis as an alternative to tracheostomy for relieving airway compromise in these rare, but difficult cases. Dr. Fritz s experience together with that of surgeons at a limited number of other centers nationwide has demonstrated that this technique can be performed safely and successfully to alter the abnormal anatomic relationships underlying tongue base obstruction in newborns with Pierre Robin sequence and thereby avoid the need for tracheostomy. The application of distraction osteogenesis for this indication has been groundbreaking and has yielded miraculous results. By performing surgery that carries a low operative morbidity, we are able in a relatively short time to establish Osteogenesis a Safe, Effective Alternative to Tracheostomy in Select Neonates with Pierre Robin Sequence The complication rates associated with distraction osteogenesis of the mandible in these very young patients have been low. more normal anatomy and a safe airway, thus obviating placement of a tracheostomy tube with its accompanying risks, need for ongoing care and adverse effects on socialization and development, Dr. Fritz says. At The Cleveland Clinic, children with Pierre Robin sequence are identified as candidates for distraction osteogenesis of the mandible through careful evaluation to document clinical evidence of severe airway obstruction and with endoscopic examination. Three-dimensional CT scans of the mandible are obtained as an aid to surgical planning. New technology for performing mandibular distraction has been introduced recently. However, in very young children, the best results are achieved using external distractors. The surgery requires an external incision for access to the mandible and involves creation of the cortical osteotomies to separate the bone segments with placement of pins on either side to hold the distractor. Distraction to stretch the osteotomies is begun after a latency period of 48 to 72 hours and performed at a rate of about 1.5 mm/day. Once the endpoint of distraction is reached, the distractor is left in place for approximately four weeks while the regenerated tissue consolidates. The distractor is then removed. We have performed this surgery within the first week of life in newborns weighing as little as 2.3 kilograms, and it can be fairly demanding technically due to the small size of these patients and because the bone can be eggshell thin. However, a good outcome is possible with careful planning and meticulous intraoperative technique that will assure free movement of the bone while avoiding injury to the tooth buds and the inferior alveolar nerve, Dr. Fritz says. The complication rates associated with distraction osteogenesis of the mandible in these very young patients have been low, and while the longest available follow-up is only about seven years, so far the toothbearing segments appear to be preserved and no nerve or other permanent damage has been recorded. Some of the biggest outstanding safety questions relate to whether there will be any long-term sequelae on mandibular and tooth growth. From a theoretical perspective, one would expect to encounter at least some minor tooth growth problems, but because these children have such small mandibles, problems with tooth growth and crowding are also seen in undistracted children. In my mind, any potential for exacerbating those problems with this surgery are far outweighed by the benefits of avoiding tracheostomy, Dr. Fritz says. Distraction osteogenesis of the mandible for treatment of these infants is evolving, and techniques and technology may be completely different in a decade as advances are made in distractors and perhaps with the introduction of biological adjuncts to accelerate and optimize bone healing, he believes. 8 Head and Neck Institute

9 meet Marshall Strome, M.D., M.S., F.A.C.S. Chairman & Professor Head and Neck Institute Clinical Interests: head and neck surgery with special interests in laryngology; thyroid and parathyroid surgery 216/ OUR staff (as of August 2005) Ramon Esclamado, M.D. Vice Chairman and Professor Clinical Interests: head and neck surgery; micro-vascular reconstruction; laryngotracheal reconstruction 216/ Tom Abelson, M.D. Solon and Beachwood Family Health Centers Clinical Interests: voice medicine; pediatric otolaryngology; sinus disease; general otolaryngology 440/ / Edward Fine, M.D., Ph.D. Westlake Family Health Center Clinical Interests: laryngology; sinonasal disease; facial cosmetics and reconstruction 440/ / Daniel Alam, M.D. Richard Freeman, M.D., Ph.D. Westlake Family Health Center Clinical Interests: general otolaryngology; head and neck surgery; sinonasal disease 440/ / Section Head, Aesthetic and Reconstructive Surgery Clinical interests: plastic and reconstructive surgery; facial aesthetic surgery; head and neck microvascular reconstruction; facial paralysis 216/ Gilberto Alemar, M.D. Cleveland Clinic Florida in Weston Clinical Interests: surgery of the nose and sinuses; sinusitis; voice and swallowing disorders; head and neck tumor surgery; sleep apnea and snoring; surgery for airway reconstruction 954/ / Michael Fritz, M.D. Clinical Interests: head and neck reconstructive surgery; soft tissue and microvascular reconstruction; rhinoplasty 216/ Joint appointment: MetroHealth Medical Center Steven Ball, M.D. Strongsville Family Health and Surgery Center Clinical Interests: general otolaryngology 440/ / Donald Goldberg, Ph.D. Hillcrest Hospital Clinical Interests: audiologic (aural) rehabilitation; cochlear implants; auditory-verbal therapy; pediatric and educational audiology; communication assessment of children and adults who are deaf or hard of hearing 440/ / Pete Batra, M.D. Clinical Interests: paranasal sinus disease; sinonasal tumors; CSF leaks; allergy 216/ David Greene, M.D. Head of Otolaryngology Cleveland Clinic, Florida in Naples Clinical interests: sleep apnea and snoring surgery; rhinoplasty; facial plastic surgery; endoscopic sinus surgery; laser surgery; facelift, blepharoplasty; skin cancer surgery and reconstruction; minimally invasive facial rejuvenation Martin Citardi, M.D. Section Head, Nasal and Sinus Disorders Clinical Interests: revision sinus surgery; frontal sinus surgery; sinonasal neoplasia; computer-aided sinus surgery; endoscopic orbital decompression; endoscopic CSF leak repair 216/ / / Catherine Henry, M.D. Clinical Interests: medical otolaryngology; preventive medicine; women s health issues; asthma 216/ Joint Appointment: General Internal Medicine Head and Neck Institute 9

10 meet our staff continued (as of August 2005) Douglas Hicks, Ph.D. Robert Lorenz, M.D. Clinical Interests: voice science; voice disorders; care of the professional voice Clinical Interests: vocal cord paralysis; head and neck oncology; laryngotracheal reconstruction; skull base tumors Section Head, Speech and Language Pathology Director, Voice Center 216/ Keiko Hirose, M.D. Section Head, Pediatric Otolaryngolog y Clinical Interests: pediatric ear surgery; hearing loss evaluation; cochlear implantation; basic science research in causes of deafness; general pediatric otolaryngology 216/ Section Head, Head and Neck Surgery 216/ Claudio Milstein, Ph.D. Clinical Interests: voice disorders; care of the professional voice; aerodigestive tract disorders; laryngeal physiology; functional dysphonia; vocal cord dysfunction 216/ Gordon Hughes, M.D. Craig Newman, Ph.D. Clinical Interests: ear surgery for deafness and infection; facial paralysis; immunology of the ear; pediatric ear diseases; vertigo diagnosis and management; tumors of the ear Clinical Interests: geriatric communication disorders; tinnitus; evoked potentials; hearing aids; outcomes research Section Head, Otology and Professor 216/ Section Head, Audiology and Professor 216/ Steve Hunyadi Jr., M.D. Wooster Clinic Clinical Interests: general otolaryngology; sinonasal disease and allergy; head and neck surgery; plastic and reconstructive surgery; pediatrics 330/ / George Ozbardakci, M.D. Lorain Family Health and Surgery Center Clinical Interests: sinus problems; hearing loss; hearing aids; snoring; sleep apnea; tonsils and adenoids 440/ / Robert Katz, M.D. Jay Roberts, M.D. Cleveland Clinic Florida in Naples Clinical Interests: thyroid and parathyroid surgery; otology; head and neck surgery 239/ / Section Head, Community Otolaryngology and Clinical Professor Solon Family Health Center Clinical Interests: pediatric otolaryngology; otology; head and neck surgery; general otolaryngology 440/ / Alan Kominksy, M.D. Beachwood Family Health Center and Main Campus Clinical Interests: adult and pediatric general otolaryngology; sinonasal disease 216/ Sharon Sandridge, Ph.D. Clinical Interests: electrophysiologic assessment; state-of-the-art amplification options including assistive listening devices and digital hearing aids; tinnitus and older adults 216/ Paul Krakovitz, M.D. Clinical Interests: pediatric otolaryngology; head and neck disease; sinus disease; airway; voice and thyroid disorders 216/ Beachwood 216/ Joseph Scharpf, M.D. Hillcrest Hospital and Main Campus Clinical Interests: Head and neck cancer and reconstructive surgery; general adult and pediatric otolaryngology 440/ / Head and Neck Institute

11 meet our staff continued (as of August 2005) Suyu Shu, Ph.D. Research Interests: cellular immunology; cancer immunotherapy; molecular biology 216/ / Joint Appointment: Director, Center for Surgery Research Judith White, M.D., Ph.D. Section Head, Vestibular and Balance Disorders Clinical Interests: vestibular disorders; dizziness and balance; hearing problems; ear disease; vertigo 216/ Beachwood 216/ Peter Weber, M.D. Program Director and Professor Clinical Interests: surgery for pediatric and adult ear disease including cochlear implants; implantable hearing aids; infectious cholesteatomas; acoustic neuromas; ear tumors; skull bone lesions; facial nerve disorders and vertigo 216/ Benjamin G. Wood, M.D. Clinical Interests: oncologic surgery of the head and neck; skull base surgery; nasal/paranasal sinus surgery 216/ introducing new staff Joseph Scharpf, M.D. Joseph Scharpf, M.D., joined the staff of The Cleveland Clinic Head and Neck Institute in July. He will be seeing patients at Hillcrest Hospital and the main campus. Dr. Scharpf specializes in head and neck cancer and reconstructive surgery, but he also sees adult and pediatric patients for general otolaryngological care issues. Dr. Scharpf received his medical degree from The Ohio State University s College of Medicine in 1998, and went on to complete a general surgery internship and a head and neck surgery residency at The Cleveland Clinic. He is returning to the Clinic after completing a one-year fellowship in oncologic and reconstructive surgery. Dr. Scharpf is board certified by the American Academy of Otolaryngology-Head and Neck Surgery and is a member of that professional association as well as of the American Rhinologic Society, the American Academy of Otolaryngologic Allergy and the American Academy of Facial Plastic and Reconstructive Surgeons. He has also been actively involved in clinical and basic science research studies focusing on nerve regeneration and head and neck cancer and reconstruction. Donald M. Goldberg, Ph.D. Donald M. Goldberg, Ph.D., joined The Cleveland Clinic Head and Neck Institute in July as co-director of the new Hearing Implant Program at Hillcrest Hospital. Dr. Goldberg received his doctorate in 1985 from the University of Florida. He holds a Certificate of Clinical Competence from the American Speech-Language-Hearing Association in both audiology and speech-language pathology and is certified by Auditory-Verbal International (AVI) as an Auditory- Verbal Therapist. Dr. Goldberg comes to the Clinic from the College of Wooster (Ohio), where he was an Associate Professor and Director of the Freedlander Speech and Hearing Clinic. Prior to that, he was Executive Director of the Helen Beebe Speech and Hearing Center in Easton, Pa. He also worked as a speechlanguage pathologist, audiologist and auditory-verbal therapist in elementary school and medical center settings, and served as faculty or a visiting instructor at several colleges/universities across the country. Head and Neck Institute 11

12 Otolaryngology Advances Fa l l Otolaryngology Advances offers information from Cleveland Clinic otolaryngologists, speech pathologists and audiologists about state-of-the-art medical, surgical and rehabilitative techniques. Please direct correspondence to: Tom Abelson, M.D. Medical Editor Head and Neck Institute / A71 The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, OH Sue Omori Marketing Manager Beth Thomas Hertz Editor Barbara Ludwig Coleman Art Director Don Gerda Photographer Established in 1921, The Cleveland Clinic Foundation provides state-of-the-art care in a multispecialty academic medical center that integrates clinical and hospital care with research and education in a private, not-for-profit group practice. Otolaryngology and Communicative Disorders services are offered at the main campus as well as at Cleveland Clinic family health centers throughout Greater Cleveland. Otolaryngology Advances is written for physicians and should be relied upon for medical education purposes only. It does not provide a complete overview of the topics covered, and should not replace the independent judgment of a physician about the appropriateness or risks of a procedure for a given patient. The Cleveland Clinic Foundation 2005 November course to focus on Nasal And Sinus Disorders The Cleveland Clinic Head and Neck Institute s Advanced Rhinology Concepts is a comprehensive three-day examination of contemporary issues in nasal and sinus disorders. It will be Nov at the Intercontinental Hotel & MBNA Conference Center on The Cleveland Clinic s main campus. Course directors are Martin J. Citardi, M.D., and Pete S. Batra, M.D. The course is for practicing otorhinolaryngologists and current residents. Diagnosis, pathophysiology and treatment of chronic rhinosinusitis, sinonasal polyposis and allergic rhinitis as well as contemporary frontal sinus surgical techniques and advances in fungal rhinosinusitis will be explored. Postoperative care and practice management strategies for the general otolaryngologist, advanced technology, including image-guided How to Refer Patients Physicians can schedule appointments for their patients at The Cleveland Clinic Head and Neck Institute by calling 216/ from 7 a.m. to 11 p.m., seven days a week, or toll-free at 800/ Visit our Web site at clevelandclinic.org/otol/ surgery, and innovative techniques in management of sinonasal neoplasia, headache and pediatric rhinosinusitis will be discussed. Demonstration dissection sessions will highlight endoscopic surgery of the paranasal sinuses. There is limited enrollment in a full cadaveric dissection laboratory with image guidance. Participants are encouraged to bring digital images (CT & MRI ) for discussion. Frederick A. Kuhn, M.D., of the Georgia Nasal & Sinus Institute in Savannah, Ga., and Daniel Hamilos, M.D., of Massachusetts General Hospital s Division of Rheumatology, Allergy and Immunology, Boston, are among guest speakers. Visit call 216/ or info@sinuscourse.com for more information. Otolaryngolog y Advances Head and Neck Institute / A71 The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, OH Non-Profit Org. U.S. Postage PAID Cleveland, Ohio Permit No Save the Date! October 26-29, 2006 Crile Centennial: 100 Years of Progress in Surgery of the Neck 12 Head and Neck Institute